Marianne Hiorth

• Cuk, Ana; Vingen, Hans Vangsnes; Sande, Sverre Arne & Hiorth, Marianne (2026). Development of an injectable, in situ formed hydrogel for controlled delivery of local anesthetics by exploiting synergism between thermoresponsive block copolymers and alginate, chitosan, or hyaluronate. Carbohydrate Polymer Technologies and Applications. 14. doi: 10.1016/j.carpta.2026.101158. Full text in Research Archive
• Vingen, Hans Vangsnes; Ćuk, Ana; Sauter, Axel Rudolf; Spigset, Olav; Andersen, Finn Husøy & Skedsmo, Fredrik [Show all 11 contributors for this article] (2026). Prolonging peripheral ropivacaine nerve block with an in situ-formed hydrogel carrier: randomized controlled trial in an ovine model. Regional anesthesia and pain medicine. ISSN 1098-7339. doi: 10.1136/rapm-2026-108092. Full text in Research Archive Show summary

  Background Local anesthetics are effective for regional anesthesia but have a relatively short duration of action. This motivates the development of sustained-release delivery systems. The aim of this study was to evaluate whether an in situ-forming hydrogel composed of poloxamers and alginate could prolong the duration of ropivacaine-induced sensory and motor blockade. Methods In this randomized and blinded two-period cross-over study, 10 female sheep received ultrasound-guided sciatic nerve injections of either 200 mg ropivacaine poloxamer-alginate hydrogel (Rop-HG) or 200 mg, as a control, plain ropivacaine solution (Rop-C). Sensory and motor functions were assessed repeatedly using a standardized clinical scoring system. Plasma ropivacaine concentrations were measured over time, and postmortem histopathological evaluation of the sciatic nerve and surrounding tissues was performed. Results Rop-HG markedly prolonged block duration compared with Rop-C, increasing the median (IQR) sensory block from 24 hours (IQR 16–36) to 60 hours (IQR 60–72) and the median motor block from 16 hours (IQR 16–18) to 60 hours (IQR 36–72). Pharmacokinetic analysis showed a sharp early peak for Rop-C (median C max 5101 nmol/L and median T max 0.33 hours), whereas Rop-HG produced a lower and delayed profile (median C max 558 nmol/L and median T max  8 hours). Histopathology revealed more pronounced and persistent local tissue reactions in Rop-HG-treated limbs, characterized by degeneration, necrosis, and inflammation. Conclusion Ultrasound-guided perineural injections of 200 mg Rop-HG substantially prolonged the clinical duration of sciatic nerve block and reduced early systemic exposure compared with a 200 mg plain ropivacaine solution. However, the formulation was associated with severe local tissue degeneration, necrosis, and inflammation. Consequently, it remains unclear whether the prolonged clinical effect resulted from a sustained pharmacological release of ropivacaine or from the local tissue toxicity. Further optimization of the formulation is required before clinical translation.

• Johnsen, Hennie Marie; Nguyen, Maria Tuyet Nhi; Larsen, Tove; Filtvedt, Werner Olav; Hiorth, Marianne & Klaveness, Jo (2026). Innovative oral formulations with silicon nanoparticles for co-delivery of poorly soluble drugs and hydrogen gas. International Journal of Pharmaceutics. ISSN 0378-5173. 697. doi: 10.1016/j.ijpharm.2026.126845. Full text in Research Archive
• Pham, Aina Kristin; Hiorth, Marianne & Rongved, Pål (2025). A novel and stable formulation of powdered high-assay calcium hypochlorite as a solid precursor of the antimicrobial compound hypochlorous acid: a preformulation study. Journal of Drug Delivery Science and Technology. ISSN 1773-2247. 113. doi: 10.1016/j.jddst.2025.107292. Full text in Research Archive Show summary

  Hypochlorous acid (HOCl) has been strongly recognized in the wake of the COVID-19 pandemic. It is a well-known antimicrobial compound with a broad-spectrum effect that demonstrates excellent clinical safety results in wounds. However, stable HOCl products remain unavailable due to challenges in maintaining storage stability, particularly at higher concentrations (≥200 μg g−1) at room temperature. To address this limitation, we investigated calcium hypochlorite (Ca[OCl]2) as a stable solid precursor for in-situ HOCl generation. This paper presents comprehensive preformulation characterization data, including powder stability analysis and release kinetics, establishing the foundational parameters necessary for future product development. We have demonstrated that commercial Ca(OCl)2 granules dissolves in a buffered medium and converts to HOCl at the time of use. However, the granules convert too slowly and may jeopardize user-friendliness. Through a mixed multivariate experimental design, we found that grinding the granules into a powder (particle sizes between 45 and 500 μm) significantly improved the conversion rates, achieving ≥99.4 % conversion within 10 s of shaking in acetic acid buffer pH 4.3 for samples equivalent to 2000 μg g−1 HOCl. Particles sized 125–150 and 180–250 μm showed rapid dissolution, with ≥98.4 % conversion within just 1 s of shaking. Powdered Ca(OCl)2 was stable for at least 24 months at 23 °C ± 2 when stored dry (≤5 % degradation), though higher temperatures and moisture negatively affected the storage stability. Flow behavior of powdered Ca(OCl)2 was also studied by the angle of repose, Hausner's ratio and compressibility index for future production purposes of the novel formulation. Good flow was observed for powders above 250 μm in particle size, whereas the tests failed for particle size below 150 μm. In summary, these findings demonstrate that powdered Ca(OCl)2 is highly stable under the proper storage conditions, making it a promising and novel HOCl precursor formulation for combating bacterial biofilm and other topical microbial infections.

• Cuk, Ana; Sande, Sverre Arne & Hiorth, Marianne (2025). Development of an injectable, in situ formed hydrogel for controlled release of local anesthetics. Journal of Drug Delivery Science and Technology. ISSN 1773-2247. 112. doi: 10.1016/j.jddst.2025.107242. Full text in Research Archive Show summary

  Injectable hydrogels are recognized as interesting delivery systems for local anesthetics. Calcium-alginate is expected to have particularly high potential due to the well-documented biocompatibility and the assumed beneficial effect on neural tissue. Formulating an injectable calcium-alginate hydrogel is complex since the phase transition and the mechanical properties may be changed by specific drug molecules. The purpose of this study was to investigate possibilities for encapsulating lidocaine, with the focus on tuning the gelling kinetics and the viscoelastic properties to achieve gelling time between 1 and 2 min followed by controlled drug release. Rheological analysis identified the [Ca2+]/[COO−] ratio as the key factor that could be manipulated to fine-tune both the gelling time and the crosslinking density. By lowering the ratio from 15 to 10, the gelling time was prolonged from 1.61 to 2.63, and from 1.57 to 2.78 min, for 1 % (w/v) and 1.5 % (w/v) alginate, respectively. In the presence of lidocaine, the gelling times were reduced, resulting in <0.75–0.95 min for 1 % (w/v), and 1.02–1.68 min for 1.5 % (w/v) alginate. The accompanying decreases in storage moduli by lowering the ratio from 15 to 10 were almost 90 % in the drug-free formulations, and about 60 % in the presence of drug. Lidocaine affected the storage moduli in formulations with high ratio by reducing them by about 50 %. Despite the apparently reduced crosslinking density, the investigated gels displayed favorable mechanical properties and drug retention capacity, with about 80 % of lidocaine being released by Fickian diffusion during 8 h.

• Carvalho, Mariana Mazetto de; Ellefsen, Christiane Færestrand; Eltvik, Andrea Angelov; Hiorth, Marianne & Samuelsen, Anne Berit C. (2025). Chemical structure characterization of polysaccharides using diffusion ordered NMR spectroscopy (DOSY). Carbohydrate Polymers. ISSN 0144-8617. 349(Part B). doi: 10.1016/j.carbpol.2024.123021. Full text in Research Archive
• Azumah, Joseph; Vasilic, Danijela; Smistad, Gro & Hiorth, Marianne (2025). Preparation of sodium hyaluronate coated liposomes: effect of polymer molecular weight, coating concentration, amount of charged lipids and type of hydration medium on the stability. Journal of liposome research. ISSN 0898-2104. 35(2), p. 159–172. doi: 10.1080/08982104.2025.2456194. Full text in Research Archive
• Carvalho, Mariana Mazetto de; Meyer, Julia; Abahra, Wafa Subhi; Tomic, Ivana; Hiorth, Marianne & Samuelsen, Anne Berit C. (2025). Chemical structure of β-glucans from the mushrooms of Lactarius spp. for development of polysaccharide-coated liposomes. Carbohydrate Polymer Technologies and Applications. 11. doi: 10.1016/j.carpta.2025.100902. Full text in Research Archive
• Johnsen, Hennie Marie; Nasr, Seyedmehdi Hossaini; Luna, Ricardo De; Filtvedt, Werner Olav; Sailor, Michael J. & Klaveness, Jo [Show all 7 contributors for this article] (2024). Stable “snow lantern-like” aggregates of silicon nanoparticles suitable as a drug delivery platform. Nanoscale. ISSN 2040-3364. 16. doi: 10.1039/d3nr05655d. Full text in Research Archive
• Johnsen, Hennie Marie; Filtvedt, Werner Olav; Klaveness, Jo & Hiorth, Marianne (2024). Nano-strategies for advancing oral drug delivery: Porous silicon particles and cyclodextrin encapsulation for enhanced dissolution of poorly soluble drugs. International Journal of Pharmaceutics. ISSN 0378-5173. 666. doi: 10.1016/j.ijpharm.2024.124809. Full text in Research Archive
• Tzanova, Martina Martin; Larsen, Bjarke Strøm; Birolo, Rebecca; Cignolini, Sara; Tho, Ingunn & Chierotti, Michele R. [Show all 11 contributors for this article] (2024). Shifting the Focus from Dissolution to Permeation: Introducing the Meso-fluidic Chip for Permeability Assessment (MCPA). Journal of Pharmaceutical Sciences. ISSN 0022-3549. 113(5), p. 1319–1329. doi: 10.1016/j.xphs.2023.12.012. Full text in Research Archive Show summary

  In response to the growing ethical and environmental concerns associated with animal testing, numerous in vitro tools of varying complexity and biorelevance have been developed and adopted in pharmaceutical research and development. In this work, we present one of these tools, i.e., the Meso-fluidic Chip for Permeability Assessment (MCPA), for the first time. The MCPA combines an artificial barrier (PermeaPad®) with an organ-on-chip device (MIVO®) and real-time automated concentration measurements, to yield a sustainable, yet effortless method for permeation testing. The system offers three major physiological aspects, i.e., a biomimetic membrane, an optimal membrane interfacial area-to-donor-volume-ratio (A/V) and a physiological flow on the acceptor/basolateral side, which makes the MPCA an ideal candidate for mechanistic studies and excellent in vivo bioavailability predictions. We validated the method with a handful of assorted drug compounds in unstirred and stirred donor conditions, before exploring its applicability as a tool for dissolution/permeation testing on a BCS class III/I drug (pyrazinamide) crystalline adducts and BCS class II/IV (hydrocortisone) amorphous solid dispersions. The results were highly reproducible and clearly displayed the method's potential for evaluating the performance of enabling formulations, and possibly even predicting in vivo performance. We believe that, upon further development, the MCPA will serve as a useful in vitro tool that could push sustainability into pharmaceutics by refining, reducing and replacing animal testing in early-stage drug development.

• Carvalho, Mariana Mazetto de; Eltvik, Andrea Angelov; Ellefsen, Christiane Færestrand; Hiorth, Marianne & Samuelsen, Anne Berit C. (2024). Coating of liposomes with β-glucans from the king oyster mushroom (Pleurotus eryngii). Colloids and Surfaces A: Physicochemical and Engineering Aspects. ISSN 0927-7757. 700. doi: 10.1016/j.colsurfa.2024.134783. Full text in Research Archive
• Johnsen, Hennie Marie; Pokle, Anuj; Filtvedt, Werner Olav; Hiorth, Marianne; Klaveness, Jo & Sjåstad, Anja Olafsen (2024). From silicon to silica: a green chemistry approach for hollow sphere nanoparticle formation. Nanoscale Advances. 6, p. 6196–6204. doi: 10.1039/d4na00586d. Full text in Research Archive Show summary

  Herein we report on an environmentally friendly and scalable production route for hollow silica spheres (HSSs). The process is based on close to 100% conversion of non-crystalline solid Si nanoparticles ([D with combining macron] = 40 ± 9 nm) in mild alkaline solutions (pH ≤ 9.0) at ambient temperature. The Si nanoparticles are prepared using the centrifugal chemical vapor deposition (cCVD) method. Combining transmission electron microscopy (TEM) imaging and nanoparticle size analysis with hydrogen evolution data, elemental mapping, and nitrogen adsorption for surface area measurement, we show for the first time experimental data that document a Kirkendall type Si-to-HSS formation process. Our understanding is that the Si nanoparticles exposed to air form a SiO2 film, which is stable in the mild alkaline environment. Silicon from the Si nanoparticles is transported through the thin SiO2 film and is reacting with H2O/OH− species on the particle surface or in the already thickened SiO2 shell to form silicic acid that in turn rapidly gets converted to a sol–gel to continue the growing of the silica shell. We foresee that this green chemistry approach can be utilized for HSS preparation for use in batteries, insulation materials and drug delivery.

• Tzanova, Martina Martin; Nguyen, Lisa; Moretti, Federica; Grassi, Mario; Magnano, Greta Camilla & Voinovich, Dario [Show all 9 contributors for this article] (2023). Interpreting permeability as a function of free drug fraction: The case studies of cyclodextrins and liposomes. European Journal of Pharmaceutical Sciences. ISSN 0928-0987. 189. doi: 10.1016/j.ejps.2023.106559. Full text in Research Archive Show summary

  In order to solubilize poorly soluble active pharmaceutical ingredients, various strategies have been implemented over the years, including the use of nanocarriers, such as cyclodextrins and liposomes. However, improving a drug's apparent solubility does not always translate to enhanced bioavailability. This work aimed to investigate to which extent complexation with cyclodextrins and incorporation into liposomes influence drug in vitro permeability and to find a mechanistic description of the permeation process. For this purpose, we investigated hydroxypropyl-β-cyclodextrin (HP-β-CD) and phosphatidylcholine liposomes formulations of three chemically diverse compounds (atenolol, ketoprofen and hydrocortisone). We studied drug diffusion of the formulations by UV-localized spectroscopy and advanced data fitting to extract parameters such as diffusivity and bound-/free drug fractions. We then correlated this information with in vitro drug permeability obtained with the novel PermeaPadⓇ barrier. The results showed that increased concentration of HP-β-CD leads to increased solubilization of the poorly soluble unionized ketoprofen, as well as hydrocortisone. However, this net increment of apparent solubility was not proportional to the increased flux measured. On the other hand, normalising the flux over the empirical free drug concentration, i.e., the free fraction, gave a meaningful absolute permeability coefficient. The results achieved for the liposomal formulation were consistent with the finding on cyclodextrins. In conclusion, we proved the adequacy and usefulness of our method for calculating free drug fractions in the examined enabling formulations, supporting the validity of the established drug diffusion/permeation theory that the unbounded drug fraction is the main driver for drug permeation across a membrane.

• Frigaard, Julie Mari; Jensen, Janicke Liaaen; Galtung, Hilde & Hiorth, Marianne (2023). Stability and cytotoxicity of biopolymer-coated liposomes for use in the oral cavity. International Journal of Pharmaceutics. ISSN 0378-5173. 645. doi: 10.1016/j.ijpharm.2023.123407. Full text in Research Archive Show summary

  This study investigates the stability and cytotoxicity of biopolymer-coated liposomes for use in the oral cavity. Liposomes (3 mM and 6 mM) were prepared by the thin film method and hydrated with phosphate buffer (PB) or glycerol phosphate buffer (G-PB). For coating, liposomes were added to a biopolymer solution of opposite charge. Particle stability was evaluated by measuring the size, polydispersity index, and zeta potential for up to 60 weeks. In vitro interaction of fluorescent-labelled biopolymer-coated liposomes and dysplastic oral keratinocytes was analyzed by confocal microscopy. Potential cytotoxicity was assessed in dysplastic oral keratinocytes by cell proliferation and cell viability. All three biopolymers showed good coating abilities for both concentrations and hydration media. The alginate coated liposomes in PB, 3 mM chitosan-coated liposomes in PB, and chitosan-coated liposomes in G-PB were stable for up to 60 weeks. In vitro studies demonstrated low cytotoxicity for all coated liposomes and non-specific cellular uptake of biopolymer-coated liposomes, independent of biopolymer, surface charge, lipid concentration and hydration media. All three formulations demonstrated low cytotoxicity and were considered safe. Alginate- and chitosan-coated liposomes demonstrated good stability over time and may be promising agents for use in the oral cavity and should be investigated further.

• Ellefsen, Christiane Færestrand; Struzek, Anna-Maria; Scherliess, Regina; Hiorth, Marianne & Samuelsen, Anne Berit C. (2023). Preparation of Albatrellus ovinus β-Glucan Microparticles with Dectin-1a Binding Properties. ACS Applied Bio Materials (AABM). 6(5), p. 1863–1872. doi: 10.1021/acsabm.3c00071. Full text in Research Archive Show summary

  Fungal β-glucans are compounds with the potential to activate the innate immune system, in part through binding to the receptor dectin-1. In the present study, small-scale methods for preparing dectin-1a binding microparticles from Albatrellus ovinus alkali-soluble β-glucans were investigated. Mechanical milling was time-consuming and yielded large particles with wide size distributions. Precipitation was more successful: the β-glucan was dissolved in 1 M NaOH, diluted, and precipitated in 1:1 mol equiv HCl. This yielded particles in sizes ranging from 0.5–2 μm. The dectin-1a binding activity was determined using HEK-Blue reporter cells. The prepared particles were able to bind to dectin-1a to the same extent as baker’s-yeast-derived β-glucan particles. The precipitation method was convenient as a quick method for small-scale preparation of β-glucan microparticle dispersions from mushroom β-glucans.

• Hiorth, Marianne; Mihailovic, Ljubica; Adamczak, Malgorzata Iwona; Goycoolea, Francisco M. & Sarkar, Anwesha (2023). Lubricating Performance of Polymer-Coated Liposomes. Biotribology. ISSN 2352-5738. 35-36. doi: 10.1016/j.biotri.2023.100239. Full text in Research Archive Show summary

  Dry mouth is a troublesome condition linked to lubrication failure and leads to other diseases such as fungal infections and wounds in the oral cavity. There are many commercial salivary substitutes in the market, but none with a long-lasting lubrication effect. Polymer-coated liposomes can be an interesting formulation strategy for retrieving the symptoms of dry mouth by mimicking the micelles of saliva. In the present study, polymer coated-liposomes were prepared by the conventional thin film method and subsequently coated with three different polymers with different charge densities; alginate, chitosan and hydrophobically modified ethyl hydroxyethyl cellulose (HM-EHEC). The prepared polymer-coated liposomes were studied concerning their lubricating properties using a ball-on-disc tribometer at 2 N load at 37 °C, and their flow behaviours were also measured. Solutions of the pure polymers and dispersions of the uncoated liposomes were also studied to investigate any contributions from the individual components. A commercial dry mouth product based on HEC (hydroxyethyl cellulose) and glycerol was also included. The formulations were measured as soon as possible after preparation and some of them after >4 weeks. Results demonstrated that all the positively-charged formulations (chitosan, positive liposomes and chitosan-coated liposomes) had superior lubricating properties with friction coefficients (μ < 0.1) at orally relevant speeds (50 mm/s) as compared to the neutral or negatively-charged systems. At boundary lubrication conditions (3 mm/s), the chitosan-coated liposomes obtained an even lower friction force than the individual components, thus indicating a synergistic effect between the polymer and the liposome.

• Ellefsen, Christiane Færestrand; Lindstad, Linda; Klau, Leesa Jane; Aachmann, Finn Lillelund; Hiorth, Marianne & Samuelsen, Anne Berit C. (2023). Investigation of the structural and immunomodulatory properties of alkali-soluble β-glucans from Pleurotus eryngii fruiting bodies. Carbohydrate Polymers. ISSN 0144-8617. 322. doi: 10.1016/j.carbpol.2023.121367. Full text in Research Archive Show summary

  Fungal β-glucans have received a lot of interest due to their proinflammatory activity towards cells of the innate immune system. Although commonly described as (1➔3)-β-glucans with varying degree of (1➔6)-branching, the fungal β-glucans constitute a diverse polysaccharide class. In this study, the alkali-soluble β-glucans from the edible mushroom Pleurotus eryngii were extracted and characterized by GC, GC–MS and 2D NMR analyses. The extracts contain several structurally different polysaccharides, including a (1➔3)-β-d-glucan with single glucose units attached at O-6, and a (1➔6)-β-d-glucan, possibly branched at O-3. The immunomodulatory activities of the P. eryngii extracts were assessed by investigating their ability to bind to the receptor dectin-1, and their ability to induce production of the proinflammatory cytokines TNF-α, IL-6 and IL-1β in LPS-differentiated THP-1 cells. Although the samples were able to bind to the dectin-1a receptor, they did not induce production of significant levels of cytokines in the THP-1 cells. Positive controls of yeast-derived (1➔3)-β-d-glucans with branches at O-6 induced cytokine production in the cells. Thus, it appears that the P. eryngii β-glucans are unable to induce production of proinflammatory cytokines in LPS-differentiated THP-1 cells, despite being able to activate the human dectin-1a receptor.

• Johnsen, Hennie Marie; Hiorth, Marianne & Klaveness, Jo (2023). Molecular Hydrogen Therapy—A Review on Clinical Studies and Outcomes. Molecules. ISSN 1431-5157. 28(23). doi: 10.3390/molecules28237785. Full text in Research Archive Show summary

  With its antioxidant properties, hydrogen gas (H2) has been evaluated in vitro, in animal studies and in human studies for a broad range of therapeutic indications. A simple search of “hydrogen gas” in various medical databases resulted in more than 2000 publications related to hydrogen gas as a potential new drug substance. A parallel search in clinical trial registers also generated many hits, reflecting the diversity in ongoing clinical trials involving hydrogen therapy. This review aims to assess and discuss the current findings about hydrogen therapy in the 81 identified clinical trials and 64 scientific publications on human studies. Positive indications have been found in major disease areas including cardiovascular diseases, cancer, respiratory diseases, central nervous system disorders, infections and many more. The available administration methods, which can pose challenges due to hydrogens’ explosive hazards and low solubility, as well as possible future innovative technologies to mitigate these challenges, have been reviewed. Finally, an elaboration to discuss the findings is included with the aim of addressing the following questions: will hydrogen gas be a new drug substance in future clinical practice? If so, what might be the administration form and the clinical indications?

• Nguyen, Sanko & Hiorth, Marianne (2023). Intraorale formuleringer - moderne produkter og potensialet i fremtidige nanobaserte formuleringer. Norsk Farmaceutisk Tidsskrift (NFT). ISSN 0029-1935. 5, p. 22–27. Full text in Research Archive Show summary

  Hensikt: Lokalbehandling av munnhulen er svært utfordrende samtidig som helseproblemer i munnhulen er et økende problem i befolkningen. Hensikten med denne oversiktsartikkelen er å gi et innblikk i moderne administrasjonssystemer som finnes på markedet i dag til behandling av orale sykdommer, og hva som kan forventes å finnes i fremtiden med fokus på nanobaserte systemer. Kunnskapsgrunnlag: Oversikten er basert på systematisk legemiddelsøk i databasene til Legemiddelverket, EMA og FDA og ved artikkelsøk i Web of Science (usystematisk). Resultater: Det finnes flere markedsførte innovative administrasjonssystemer som imøtekommer det største problemet ved lokalbehandling av munnhulen; nemlig kort oral oppholdstid. Disse baserer seg på prinsippet om bioadhesjon som gjør at formuleringene kleber seg godt til en biologisk overflate, for eksempel slimhinne, ved bruk av bioadhesive polymermaterialer. Til tross for økende behov for nye formuleringer for mer optimal lokalbehandling av munnhulen, er det gjort forholdsvis lite forskning på dette området. Studier som er publisert, omtaler nanopartikulære formuleringer som potensielle nye administrasjonssystemer til munnhulen. Her er hovedprinsippet også bioadhesjon. Dette oppnås ved bruk av biopolymerer og omfatter flere typer bærere som nanosfærer og biopolymerdekkede liposomer og polykaprolaktonpartikler. Konklusjon: Sannsynligheten er stor for at det i fremtiden vil finnes nanobaserte, bioadhesive administrasjonssystemer til lokalbehandling av munnhulen.

• Frigaard, Julie Mari; Jensen, Janicke Liaaen; Galtung, Hilde & Hiorth, Marianne (2022). The Potential of Chitosan in Nanomedicine: An Overview of the Cytotoxicity of Chitosan Based Nanoparticles. Frontiers in Pharmacology. 13. doi: 10.3389/fphar.2022.880377. Full text in Research Archive Show summary

  The unique properties and applications of nanotechnology in targeting drug delivery, cosmetics, fabrics, water treatment and food packaging have received increased focus the last two decades. The application of nanoparticles in medicine is rapidly evolving, requiring careful investigation of toxicity before clinical use. Chitosan, a derivative of the natural polysaccharide chitin, has become increasingly relevant in modern medicine because of its unique properties as a nanoparticle. Chitosan is already widely used as a food additive and in food packaging, bandages and wound dressings. Thus, with an increasing application worldwide, cytotoxicity assessment of nanoparticles prepared from chitosan is of great interest. The purpose of this review is to provide an updated status of cytotoxicity studies scrutinizing the safety of chitosan nanoparticles used in biomedical research. A search in Ovid Medline from 23 March 1998 to 4 January 2022, with the combination of the search words Chitosan or chitosan , nanoparticle or nano particle or nanosphere or nanocapsule or nano capsule , toxicology or toxic or cytotoxic and mucosa or mucous membrane resulted in a total of 88 articles. After reviewing all the articles, those involving non-organic nanoparticles and cytotoxicity assays conducted exclusively on nanoparticles with anti-tumor effect (i.e., having cytotoxic effect) were excluded, resulting in 70 articles. Overall, the chitosan nanoparticles included in this review seem to express low cytotoxicity regardless of particle composition or cytotoxicity assay and cell line used for testing. Nonetheless, all new chitosan derivatives and compositions are recommended to undergo careful characterization and cytotoxicity assessment before being implemented on the market.

• Johnsen, Hennie Marie; Filtvedt, Werner Olav; Hiorth, Marianne & Klaveness, Jo (2022). Silicon nanoparticles for oral administration of molecular hydrogen. International Journal of Pharmaceutics. ISSN 0378-5173. 629. doi: 10.1016/j.ijpharm.2022.122371. Full text in Research Archive Show summary

  Medical use of hydrogen gas (H2) has been given increasing attention over the past 15 years with numerous clinical trials for a variety of indications. The biological activity of H2 includes antioxidant properties and thereby the ability to neutralize damaging reactive oxygen species (ROS). Administration of hydrogen as a medical gas is limited by the poor water solubility and by the flammability of H2 in air. Therefore, nanocarriers have been investigated for safer and more efficient administration of hydrogen. Silicon particles are suggested for oral administration with the ability to undergo a redox reaction with water to produce H2 in vivo. The purpose of this work was to investigate the hydrogen generating abilities of silicon particles synthesized by centrifugal chemical vapor deposition (cCVD). High hydrogen generation rates up to 1310 ml/g at physiological pH 7.4 (82 % yield) were observed. An in vitro model of oral administration showed that pretreatment in artificial gastric juice did not affect hydrogen generation. Thus, the cCVD silicon particles seem to be suitable for in vivo hydrogen generation. A surface carbon coating or addition of surfactants or albumin hindered hydrogen generation. The addition of egg white reduced hydrogen generation but did not block it.

• Azumah, Joseph; Smistad, Gro & Hiorth, Marianne (2022). Preparation of stable polymer-liposome complexes by a novel approach employing a one-pot method. Colloids and Surfaces A: Physicochemical and Engineering Aspects. ISSN 0927-7757. 653. doi: 10.1016/j.colsurfa.2022.129924. Full text in Research Archive Show summary

  The purpose of this study was to prepare stable polymer-liposome complexes using a new, improved one-pot method. Complexes prepared by the conventional method were used as reference. The one-pot method combines the vesicle formation and complexation with the polymer in a single step allowing for fewer steps compared to the conventional thin-film method followed by coating. This has the possibility of complexing the polymer on the surface and within the aqueous core of the liposomes. Soya phosphatidylcholine (SoyPC) in combination with different amounts of either dioleoyl trimethylammoniumpropane (DOTAP, positively charged) or egg phosphatidylglycerol (Egg PG, negatively charged) were complexed with alginate or chitosan, respectively. All the alginate-liposome complexes were larger compared to the naked liposomes and the zeta potential changed from positive to negative after complexation with the polymer. Polydispersity index (PDI) analysis showed narrow size distributions implying homogenous populations. The best stability was obtained by employing 20 mol% DOTAP in the membrane. This formulation was stable during the whole four months period when the stability test was performed. The chitosan-liposome complexes were generally difficult to extrude and were larger than the alginate-liposome complexes due to the need for a larger pore size in the membrane during extrusion. Based on these results, the one-pot method can be used for preparing stable alginate-liposome complexes. For the chitosan-liposome complexes alternative methods for size reduction should be investigated.

• Tzanova, Martina Martin; Moretti, Federica; Grassi, Gabriele; Stein, Paul; Hiorth, Marianne & Abrami, Michela [Show all 8 contributors for this article] (2022). Modelling drug diffusion through unstirred water layers allows real-time quantification of free/loaded drug fractions and release kinetics from colloidal-based formulations. European journal of pharmaceutics and biopharmaceutics. ISSN 0939-6411. 178, p. 168–178. doi: 10.1016/j.ejpb.2022.08.009. Full text in Research Archive Show summary

  The correlation between in vivo and in vitro data is yet not sufficiently optimized to allow a significant reduction and replacement of animal testing in pharmaceutical development. One of the main reasons for this lies in the poor mechanistic understanding and interpretation of the physical mechanisms enabling formulation rely on for deploying the drug. One mechanism that still lacks a proper interpretation is the kinetics of drug release from nanocarriers. In this work, we investigate two different types of classical enabling formulations – i) cyclodextrin solutions and ii) liposomal dispersions – by a combination of an experimental method (i.e. UV–Vis localized spectroscopy) and mathematical modelling/numerical data fitting. With this approach, we are able to discriminate precisely between the amount of drug bound to nanocarriers or freely dissolved at any time point; in addition, we can precisely estimate the binding and diffusivity constants of all chemical species (free drug/bound drug). The results obtained should serve as the first milestone for the further development of reliable in vitro/in silico models for the prediction of in vivo drug bioavailability when enabling formulations are used.

• Tzanova, Martina Martin; Randelov, Elizabeta; Stein, Paul C.; Hiorth, Marianne & Cagno, Massimiliano Pio Di (2021). Towards a better mechanistic comprehension of drug permeation and absorption: Introducing the diffusion-partitioning interplay. International Journal of Pharmaceutics. ISSN 0378-5173. 608. doi: 10.1016/j.ijpharm.2021.121116. Full text in Research Archive Show summary

  The process of passive drug absorption from the gastrointestinal tract is still poorly understood and modelled. Additionally, the rapidly evolving field of pharmaceutics demands efficient, affordable and reliable in vitro tools for predicting in vivo performance. In this work, we combined established methods for quantifying drug diffusivity (localized UV-spectroscopy) and permeability (Permeapad® plate) in order to gain a better understanding of the role of unstirred water layers (UWLs) in drug absorption. The effect of diffusion/permeability media composition and viscosity on the apparent permeation resistance (Rapp) of model drugs caffeine (CAF) and hydrocortisone (HC) were tested and evaluated by varying the type and concentration of viscosity-enhancing agent – glycerol or a poly(ethylene glycol) (PEG) with different average molecular weights. For all types of media, increased viscosity lead to reduction in diffusivity but could not alone explain the observed effect, which was attributed to intermolecular polymer-drug interactions. Additionally, for both drugs, smaller hydrophilic viscosity-enhancing agents (glycerol and PEG 400) had larger influence than larger ones (PEG 3350 and 6000). The results highlighted the role of UWL as an additive barrier to permeation and indicated that diffusion through UWL is the rate-limiting step to CAF’s permeation, whilst HC permeability is a partition-driven process.

• Hagesæther, Ellen; Adamczak, Malgorzata Iwona; Hiorth, Marianne & Tho, Ingunn (2020). Characterization of Bioadhesion, Mucin‐interactions and Mucosal Permeability of Pharmaceutical Nano‐ and Microsystems. In Peltonen, Leena (Eds.), Characterization of Pharmaceutical Nano and Microsystems. John Wiley & Sons. ISSN 9781119414018. p. 171–205. doi: 10.1002/9781119414018.ch5. Full text in Research Archive
• Che, Loan Trinh; Hiorth, Marianne; Hoogenboom, Richard & Kjøniksen, Anna-Lena (2020). Complex temperature and concentration dependent self-assembly of poly(2-oxazoline) block copolymers. Polymers. 12:1495(7), p. 1–16. doi: 10.3390/polym12071495. Full text in Research Archive Show summary

  The effect of polymer concentration on the temperature-induced self-association of a block copolymer comprising a poly(2-ethyl-2-oxazoline) block and a random copolymer block consisting of 2-ethyl-2-oxazoline and 2-n-propyl-2-oxazoline (PEtO80-block-P(EtOxx-stat-PropO40-x) with x = 0, 4, or 8 were investigated by dynamic light scattering (DLS) and transmittance measurements (turbidimetry). The polymers reveal a complex aggregation behavior with up to three relaxation modes in the DLS data and with a transmittance that first goes through a minimum before it declines at high temperatures. At low temperatures, unassociated polymer chains were found to co-exist with larger aggregates. As the temperature is increased, enhanced association and contraction of the aggregates results in a drop of the transmittance values. The aggregates fragment into smaller micellar-like clusters when the temperature is raised further, causing the samples to become optically clear again. At high temperatures, the polymers aggregate into large compact clusters, and the samples become turbid. Interestingly, very large aggregates were observed at low temperatures when the polymer concentrations were low. The formation of these aggregates was also promoted by a more hydrophilic copolymer structure. The formation of large aggregates with an open structure at conditions where the solvent conditions are improved is probably caused by depletion flocculation of the smaller aggregates.

• Tandberg, Julia Isabel; Rojas, Leidy Ximena Lagos; Ropstad, Erik; Smistad, Gro; Hiorth, Marianne & Winther-Larsen, Hanne Cecilie (2018). The use of chitosan-coated membrane vesicles for immunization against salmonid rickettsial septicemia in an adult zebrafish model. Zebrafish. ISSN 1545-8547. 15(4), p. 372–381. doi: 10.1089/zeb.2017.1556. Full text in Research Archive
• Cao, Vinh Duy; Bringas, Carlos Salas; Schüller, Reidar Barfod; Szczotok-Piechaczek, Anna Maria; Hiorth, Marianne & Carmona, Manuel [Show all 8 contributors for this article] (2018). Rheological and thermal properties of suspensions of microcapsules containing phase change materials. Colloid and Polymer Science. ISSN 0303-402X. 296(5), p. 981–988. doi: 10.1007/s00396-018-4316-9. Full text in Research Archive Show summary

  The thermal and rheological properties of suspensions of microencapsulated phase change materials (MPCM) in glycerol were investigated. When the microcapsule concentration is raised, the heat storage capacity of the suspensions becomes higher and a slight decline in the thermal conductivity of the suspensions is observed. The temperature-dependent shear-thinning behaviour of the suspensions was found to be strongly affected by non-encapsulated phase change materials (PCM). Accordingly, the rheological properties of the MPCM suspensions could be described by the Cross model below the PCM melting point while a power law model best described the data above the PCM melting point. The MPCM suspensions are interesting for energy storage and heat transfer applications. However, the non-encapsulated PCM contributes to the agglomeration of the microcapsules, which can lead to higher pumping consumption and clogging of piping systems.

• Mackie, Alan R.; Goycoolea, Francisco M.; Menchicchi, Bianca; Caramella, Carla Marcella; Saporito, Francesca & Lee, Seunghwan [Show all 13 contributors for this article] (2017). Innovative Methods and Applications in Mucoadhesion Research. Macromolecular Bioscience. ISSN 1616-5187. 17:1600534(8), p. 1–32. doi: 10.1002/mabi.201600534. Full text in Research Archive
• Pistone, Sara; Goycoolea, Francisco M.; Young, Alix; Smistad, Gro & Hiorth, Marianne (2017). Formulation of polysaccharide-based nanoparticles for local administration into the oral cavity. European Journal of Pharmaceutical Sciences. ISSN 0928-0987. 96, p. 381–389. doi: 10.1016/j.ejps.2016.10.012. Full text in Research Archive Show summary

  The efficacy of treatments for oral ailments is often challenged by a low residence time of the conventional pharmaceutical formulations in the oral cavity. The residence time in the oral cavity could be improved by using bioadhesive formulations, such as preparations based on polysaccharides. This study describes the formulation and the evaluation of polysaccharide-based nanosystems as drug delivery systems addressed to the oral cavity. Nanoparticles based on chitosan, alginate or pectin were prepared through self-assembly by ionotropic gelation using oppositely charged crosslinkers (tripolyphosphate or zinc). Characteristics of nanoparticles at increasing crosslinker concentration provided the basis for selecting the most suitable formulations. The nanoparticles were tested for cytotoxicity against buccal cells (TR146) and for stability in a medium simulating pH, ionic strength, electrolyte composition and concentration of saliva. Alginate nanoparticles were the most stable in the salivary environment, while chitosan nanoparticles were the most cytocompatible. Alginate nanoparticles and pectin nanoparticles revealed possible cytotoxicity due to the presence of zinc. This knowledge is important in the early design of polymer-based nanoparticles for oral usage and for potential improving of the biocompatibility of the investigated nanoparticles with the oral environment.

• Adamczak, Malgorzata Iwona; Martinsen, Ørjan Grøttem; Smistad, Gro & Hiorth, Marianne (2017). Polymer coated mucoadhesive liposomes intended for the management of xerostomia. International Journal of Pharmaceutics. ISSN 0378-5173. 527(1-2), p. 72–78. doi: 10.1016/j.ijpharm.2017.05.032. Full text in Research Archive Show summary

  The aim of this work was to prepare and test different pharmaceutical formulations in respect of their potential in relieving dry mouth symptom. Since many of the products available on the market provide only temporary relief to the patients, there is need for new formulations able to retain on the oral mucosa. The prolonged moisture protection could be achieved by combining mucoadhesive materials, such as polymers containing hydrogen bonding groups, with vesicles capable of releasing hydration medium from the inner compartment. In this study three different types of liposomes (positively, negatively and neutrally charged) were coated with five different types of polymers: low-methoxylated pectin (LM-pectin), high-methoxylated pectin (HM-pectin), alginate, chitosan and hydrophobically modified ethyl hydroxyethyl cellulose (HM-EHEC). The particle size and the zeta potential of the obtained carriers were tested by measuring dynamic light scattering (DLS) and electrophoretic mobility. Later on, selected positively charged liposomes were deposited on a negatively charged mica surface and depicted by atomic force microscopy (AFM). The water sorption properties of polymers, uncoated liposomes and polymer-coated liposomes were studied by the means of dynamic vapor sorption (DVS). The experiments were performed within the relative humidity range RH = 95–0–95%, at 35 °C. It was found that coating the liposomes with polymers significantly increased the water sorption capacity of the formulations, making them an attractive choice for hydration of the oral mucosa.

• Pistone, Sara; Rykke, Morten; Smistad, Gro & Hiorth, Marianne (2017). Polysaccharide-coated liposomal formulations for dental targeting. International Journal of Pharmaceutics. ISSN 0378-5173. 516(1-2), p. 106–115. doi: 10.1016/j.ijpharm.2016.11.028. Full text in Research Archive Show summary

  The efficacy of treatments of oral ailments is often challenged by a low residence time of the conventional pharmaceutical formulations in the oral cavity, which could be improved by using bioadhesive formulations. This in vitro study investigated charged liposomes, both uncoated and coated through electrostatic deposition with polysaccharides (chitosan, alginate and pectin), as bioadhesive systems for the oral cavity. First, formulations that provided liposomes fully coated with polysaccharide were selected. Thereafter, the stability of both the uncoated and the polysaccharide-coated liposomes was investigated in artificial saliva simulating pH, ionic strength, and ionic content of natural saliva. Additionally, adsorption to hydroxyapatite (model for tooth enamel) was tested. The surface charge was of high importance for both the stability in salivary environment and bioadhesion. In artificial saliva, the negatively charged liposomes were the most stable, and the stability of the positively charged liposomes was improved through coating with a negatively charged polysaccharide. On the contrary, the positively charged liposomes were the most bioadhesive, although a moderate adsorption was recorded for the negatively charged liposomes. Based on the present results, the negatively charged liposomes seem to be the most promising formulations used as a tooth adhesive nanosystem and could as such provide improved treatment of tooth ailments.

• Nguyen, Sanko; Escudero, Carlos; Sediqi, Nadia; Smistad, Gro & Hiorth, Marianne (2017). Fluoride loaded polymeric nanoparticles for dental delivery. European Journal of Pharmaceutical Sciences. ISSN 0928-0987. 104, p. 326–334. doi: 10.1016/j.ejps.2017.04.004. Full text in Research Archive Show summary

  The overall aim of the present paper was to develop fluoride loaded nanoparticles based on the biopolymers chitosan, pectin, and alginate, for use in dental delivery. First, the preparation of nanoparticles in the presence of sodium fluoride (NaF) as the active ingredient by ionic gelation was investigated followed by an evaluation of their drug entrapment and release properties. Chitosan formed stable, spherical, and monodisperse nanoparticles in the presence of NaF and tripolyphoshate as the crosslinker, whereas alginate and pectin were not able to form any definite nanostructures in similar conditions. The fluoride loading capacity was found to be 33–113 ppm, and the entrapment efficiency 3.6–6.2% for chitosan nanoparticles prepared in 0.2–0.4% (w/w) NaF, respectively. A steady increase in the fluoride release was observed for chitosan nanoparticles prepared in 0.2% NaF both in pH 5 and 7 until it reached a maximum at time point 4 h and maintained at this level for at least 24 h. Similar profiles were observed for formulations prepared in 0.4% NaF; however the fluoride was released at a higher level at pH 5. The low concentration, but continuous delivery of fluoride from the chitosan nanoparticles, with possible expedited release in acidic environment, makes these formulations highly promising as dental delivery systems in the protection against caries development.

• Hiorth, Marianne (2017). Improved Drug Delivery Systems for Preventing Dental Caries. Current Drug Delivery. ISSN 1567-2018. 14(4), p. 446–448. doi: 10.2174/1567201813666161014091339. Full text in Research Archive
• Smistad, Gro; Nyström, Bo; Zhu, Kaizheng; Grønvold, Marte; Røv-Johnsen, Anne & Hiorth, Marianne (2017). Liposomes coated with hydrophobically modified hydroxyethyl cellulose: Influence of hydrophobic chain length and degree of modification. Colloids and Surfaces B: Biointerfaces. ISSN 0927-7765. 156, p. 79–86. doi: 10.1016/j.colsurfb.2017.04.061. Full text in Research Archive Show summary

  Nanoparticulate systems with an uncharged hydrophilic surface may have a great potential in mucosal drug delivery. In the present study liposomes were coated with hydrophobically modified hydroxyethyl cellulose (HM-HEC) to create a sterically stabilized liposomal system with an uncharged surface. The aim was to clarify the influence of the amount of hydrophobic modification of HEC and the length of the hydrophobic moiety, on the stability of the system and on the release properties. HM-HEC with different degrees of hydrophobic modification (1 and 2 mol%) and hydrophobic groups with different chain lengths (C8, C12, C16) were included in the study, as well as fluid phase and gel phase liposomes. Both types of liposomes were successfully coated with HM-HEC containing 1 mol% of hydrophobic groups, while 2 mol% did not work for the intended pharmaceutical applications. The polymer coated gel phase liposomes were stable (size, zeta potential, leakage) for 24 weeks at 4 °C, with no differences between the C8 and C16 HM-HEC coating. For the fluid phase liposomes a size increase was observed after 24 weeks at 4 °C for all formulations; the C8 HM-HEC coated liposomes increased the most. No differences in the leakage during storage at 4 °C or in the release at 35 °C were observed between the fluid phase formulations. To conclude; HM-HEC with a shorter hydrophobic chain length resulted in a less stable product for the fluid phase liposomes, while no influence of the chain length was observed for the gel phase liposomes (1 mol% HM).

• Adamczak, Malgorzata Iwona; Hagesæther, Ellen; Smistad, Gro & Hiorth, Marianne (2016). An in vitro study of mucoadhesion and biocompatibility of polymer coated liposomes on HT29-MTX mucus-producing cells. International Journal of Pharmaceutics. ISSN 0378-5173. 498(1-2), p. 225–233. doi: 10.1016/j.ijpharm.2015.12.030. Full text in Research Archive Show summary

  Drug delivery to the oral cavity poses a significant challenge due to the short residence time of the formulations at the site of action. From this point of view, nanoparticulate drug delivery systems with ability to adhere to the oral mucosa are advantageous as they could increase the effectiveness of the therapy. Positively, negatively and neutrally charged liposomes were coated with four different types of polymers: alginate, low-ester pectin, chitosan and hydrophobically modified ethyl hydroxyethyl cellulose. The mucoadhesion was studied using a novel in vitro method allowing the liposomes to interact with a mucus-producing confluent HT29-MTX cell-line without applying any external force. MTT viability and paracellular permeability tests were conducted on the same cell-line. The alginate-coated liposomes achieved a high specific (genuine) mucin interaction, with a low potential of cell-irritation. The positively charged uncoated liposomes achieved the highest initial mucoadhesion, but also displayed a higher probability of cell-irritation. The chitosan-coated liposomes displayed the highest potential for long lasting mucoadhesion, but with the drawback of a higher general adhesion (tack) and a higher potential for irritating the cells.

• Pistone, Sara; Qoragllu, Dafina; Smistad, Gro & Hiorth, Marianne (2016). Multivariate analysis for the optimization of polysaccharide-based nanoparticles prepared by self-assembly. Colloids and Surfaces B: Biointerfaces. ISSN 0927-7765. 146, p. 136–143. doi: 10.1016/j.colsurfb.2016.05.055. Full text in Research Archive
• Nguyen, Sanko; Smistad, Gro; Rykke, Morten & Hiorth, Marianne (2016). Nanoparticulate Systems for Dental Drug Delivery. In Arias, Jose L. (Eds.), Nanotechnology and Drug Delivery - volume II: Nano-Engineering Strategies and Nanomedicines Against Severe Diseases.. CRC Press. ISSN 9781482262711. p. 52–74. doi: 10.1201/b19976-3. Full text in Research Archive
• Mirtic, Janja; Kogej, Ksenija; Baumgartner, Sasa; Smistad, Gro; Kristl, Julijana & Hiorth, Marianne (2016). Development of Cetylpyridinium-Alginate Nanoparticles: A Binding and Formulation Study. International Journal of Pharmaceutics. ISSN 0378-5173. 511(2), p. 774–784. doi: 10.1016/j.ijpharm.2016.07.065. Full text in Research Archive
• Nguyen, Sanko; Adamczak, Malgorzata Iwona; Hiorth, Marianne; Smistad, Gro & Kopperud, Hilde Beate M. (2016). Liposome adsorption to restorative materials. Dental Materials. ISSN 0109-5641. 32. doi: 10.1016/j.dental.2016.08.049. Full text in Research Archive
• Adamczak, Malgorzata Iwona; Martinsen, Ørjan Grøttem; Smistad, Gro & Hiorth, Marianne (2016). Water sorption properties of HM-pectin and liposomes intended to alleviate dry mouth. International Journal of Pharmaceutics. ISSN 0378-5173. 506(1-2), p. 201–206. doi: 10.1016/j.ijpharm.2016.04.050. Full text in Research Archive Show summary

  Pharmaceutical formulations intended for treatment of xerostomia (dry mouth) should be able to keep the oral mucosa hydrated for a prolonged period of time. The products already existing on the market contain water-soluble polymers, however their ability to moisturize the oral mucosa for a longer period of time seems limited. In this paper the sorption properties of water vapor of high-methoxylated pectin (HM-pectin, a hydrophilic biopolymer) and phosphatidylcholine-based (Soya-PC) liposomes have been studied and compared using a gravimetric method. The kinetics of water desorption and sorption have been recorded over the relative humidity range RH = 95–0–95%, at 35 °C. The obtained isotherms were found to be well described by the n-layer Brunauer-Emmet-Teller (BET) adsorption model. The water isotherms on HM-pectin were Type II (IUPAC), while water isotherms on liposomes were Type III. The maximum water sorption capacity of liposomes (1.2 mg water per mg of adsorbent at 95% RH) was found to be twice as high as for pectin. Due to the slower water release from the liposomes, as well as their high water sorption capacity, they seem to have great potential in relieving the symptoms of dry mouth syndrome.

• Klemetsrud, Therese; Kjøniksen, Anna-Lena; Hiorth, Marianne; Jacobsen, Jette & Smistad, Gro (2016). Polymer coated liposomes for use in the oral cavity – a study of the in vitro toxicity, effect on cell permeability and interaction with mucin. Journal of liposome research. ISSN 0898-2104. 28(1), p. 62–73. doi: 10.1080/08982104.2016.1255640. Full text in Research Archive
• Klemetsrud, Therese; Hiorth, Marianne; Smistad, Gro & Kjøniksen, Anna-Lena (2015). Characterization of temperature induced changes in liposomes coated with poly(N-isopropylacrylamide-co-methacrylic acid). Journal of Colloid and Interface Science. ISSN 0021-9797. 450, p. 7–16. doi: 10.1016/j.jcis.2015.03.005. Full text in Research Archive
• Nguyen, Sanko; Adamczak, Malgorzata Iwona; Hiorth, Marianne; Smistad, Gro & Kopperud, Hilde Beate M. (2015). Interactions of liposomes with dental restorative materials. Colloids and Surfaces B: Biointerfaces. ISSN 0927-7765. 136, p. 744–751. doi: 10.1016/j.colsurfb.2015.10.024. Full text in Research Archive
• Pistone, Sara; Qoragllu, Dafina; Smistad, Gro & Hiorth, Marianne (2015). Formulation and preparation of stable cross-linked alginate-zinc nanoparticles in the presence of a monovalent salt. Soft Matter. ISSN 1744-683X. 11(28), p. 5765–5774. doi: 10.1039/c5sm00700c. Full text in Research Archive
• Nguyen, Sanko & Hiorth, Marianne (2015). Advanced drug delivery systems for local treatment of the oral cavity. Therapeutic delivery. ISSN 2041-5990. 6(5), p. 197–210. doi: 10.4155/tde.15.5. Full text in Research Archive
• Hiorth, Marianne; Nilsen, Susanne & Tho, Ingunn (2014). Bioadhesive Mini-Tablets for Vaginal Drug Delivery. Pharmaceutics. 6(3), p. 494–511. doi: 10.3390/pharmaceutics6030494. Full text in Research Archive Show summary

  Different non-ionic cellulose ethers (methyl cellulose, MC; hydroxyethyl cellulose, HEC; hydroxypropyl cellulose, HPC; hydroxypropylmethyl cellulose, HPMC) and microcrystalline cellulose (MCC) were investigated as matrix formers for preparation of mini-tablets targeting vaginal drug delivery. Hexyl aminolevulinat hydrochloridum (HAL) was used as a model drug. The mini-tablets were characterized with respect to their mechanical strength, bioadhesion towards cow vaginal tissue in two independent tests (rotating cylinder test, detachment test using texture analyzer), and dissolution rate in two media mimicking the pH levels of fertile, healthy and post-menopausal women (vaginal fluid simulant pH 4.5, phosphate buffer pH 6.8). Mini-tablets with a matrix of either HPMC or HPC were found to possess adequate mechanical strength, superior bioadhesive behavior towards vaginal tissue, and pH independent controlled release of the model drug, suggesting that both systems would be suited for the treatment of women regardless of age, i.e., respective of their vaginal pH levels. Bioadhesive mini-tablets offer a potential for improved residence time in the vaginal cavity targeting contact with mucosal tissue and prolonged release of the drug.

• Meland, Hilde-Gunn; Røv-Johnsen, Anne; Smistad, Gro & Hiorth, Marianne (2014). Studies on surface coating of phospholipid vesicles with a non-ionic polymer. Colloids and Surfaces B: Biointerfaces. ISSN 0927-7765. 114, p. 45–52. doi: 10.1016/j.colsurfb.2013.09.054. Full text in Research Archive
• Nguyen, Sanko; Hiorth, Marianne; Rykke, Morten & Smistad, Gro (2013). Polymer coated liposomes for dental drug delivery - Interactions with parotid saliva and dental enamel. European Journal of Pharmaceutical Sciences. ISSN 0928-0987. 50(1), p. 78–85. doi: 10.1016/j.ejps.2013.03.004. Full text in Research Archive
• Jonassen, Helene; Treves, Alessandro; Kjøniksen, Anna-Lena; Smistad, Gro & Hiorth, Marianne (2013). Preparation of Ionically Cross-Linked Pectin Nanoparticles in the Presence of Chlorides of Divalent and Monovalent Cations. Biomacromolecules. ISSN 1525-7797. 14(10), p. 3523–3531. doi: 10.1021/bm4008474. Full text in Research Archive
• Alund, Siv Jorunn; Smistad, Gro & Hiorth, Marianne (2013). A multivariate analysis investigating different factors important for the interaction between liposomes and pectin. Colloids and Surfaces A: Physicochemical and Engineering Aspects. ISSN 0927-7757. 420, p. 1–9. doi: 10.1016/j.colsurfa.2012.11.079. Full text in Research Archive
• Hiorth, Marianne; Liereng, Linda; Selmer, Reidun Reinertsen & Tho, Ingunn (2013). Formulation of bioadhesive hexylaminolevulinate pellets intended for photodynamic therapy in the treatment of cervical cancer. International Journal of Pharmaceutics. ISSN 0378-5173. 441(1-2), p. 544–554. doi: 10.1016/j.ijpharm.2012.10.046. Full text in Research Archive
• Klemetsrud, Therese; Jonassen, Helene; Hiorth, Marianne; Kjøniksen, Anna-Lena & Smistad, Gro (2013). Studies on pectin-coated liposomes and their interaction with mucin. Colloids and Surfaces B: Biointerfaces. ISSN 0927-7765. 103, p. 158–165. doi: 10.1016/j.colsurfb.2012.10.012. Full text in Research Archive
• Jonassen, Helene; Kjøniksen, Anna-Lena & Hiorth, Marianne (2012). Effects of ionic strength on the size and compactness of chitosan nanoparticles. Colloid and Polymer Science. ISSN 0303-402X. 290(10), p. 919–929. doi: 10.1007/s00396-012-2604-3. Full text in Research Archive
• Smistad, Gro; Bøyum, Silje; Alund, Siv Jorunn; Samuelsen, Anne Berit C. & Hiorth, Marianne (2012). The potential of pectin as a stabilizer for liposomal drug delivery systems. Carbohydrate Polymers. ISSN 0144-8617. 90(3), p. 1337–1344. doi: 10.1016/j.carbpol.2012.07.002. Full text in Research Archive
• Jonassen, Helene; Kjøniksen, Anna-Lena & Hiorth, Marianne (2012). Stability of Chitosan Nanoparticles Cross-Linked with Tripolyphosphate. Biomacromolecules. ISSN 1525-7797. 13(11), p. 3747–3756. doi: 10.1021/bm301207a. Full text in Research Archive

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• Carvalho, Mariana Mazetto de; Eltvik, Andrea Angelov; Ellefsen, Christiane Færestrand; Hiorth, Marianne & Samuelsen, Anne Berit C. (2024). β-glucans from the king oyster mushroom (Pleurotus eryngii) as a novel source material for coating liposomes. Full text in Research Archive
• Carvalho, Mariana Mazetto de; Eltvik, Andrea Angelov; Ellefsen, Christiane Færestrand; Hiorth, Marianne & Samuelsen, Anne Berit C. (2023). Liposome surface coating using distinct β-glucans fractions from Pleurotus eryngii. Full text in Research Archive
• Carvalho, Mariana Mazetto de; Eltvik, Andrea Angelov; Hiorth, Marianne & Samuelsen, Anne Berit C. (2023). Development of β-glucans coated liposomes for targeting to the cells of the immune system. Full text in Research Archive
• Ellefsen, Christiane Færestrand; Struzek, Anna-Maria; Scherliess, Regina; Hiorth, Marianne & Samuelsen, Anne Berit C. (2022). Mushroom β-glucan microparticles with immuno-activating potential. Full text in Research Archive
• Frigaard, Julie Mari; Jensen, Janicke Liaaen; Galtung, Hilde & Hiorth, Marianne (2021). Development of a Liposomal Dry Mouth Product for Long-term Relief. Full text in Research Archive
• Ellefsen, Christiane Færestrand; Hiorth, Marianne & Samuelsen, Anne Berit C. (2021). Preparation of fungal β-glucan particles by acid precipitation. Full text in Research Archive
• Hiorth, Marianne; Azumah, Joseph & Smistad, Gro (2019). The potential of polymer-coated liposomes for dental care. Full text in Research Archive
• Hiorth, Marianne (2019). The potential of polymer-coated liposomes as a salivary substitute. Full text in Research Archive
• Azumah, Joseph; Hiorth, Marianne; Smistad, Gro & Martinsen, Ørjan Grøttem (2019). Development of alginate and chitosan coated liposomes intended to use in the treatment of xerostomia. Full text in Research Archive
• Azumah, Joseph; Hiorth, Marianne; Smistad, Gro & Martinsen, Ørjan Grøttem (2019). Alginate and chitosan coated liposomes intended for treatment of dry mouth. Full text in Research Archive
• Azumah, Joseph; Smistad, Gro; Martinsen, Ørjan Grøttem & Hiorth, Marianne (2019). Development of alginate coated liposomes with potential of being used in treatment of dry mouth. Full text in Research Archive
• Hiorth, Marianne (2018). The potential of nanoparticles in the combat against dry mouth. Full text in Research Archive
• Hiorth, Marianne; Adamczak, Malgorzata Iwona; Espinosa, Yadira Gonzalez; Goycoolea, Francisco M. & Sarkar, Anwesha (2018). Lubricating properties of polymer coated liposomes. Full text in Research Archive
• Hiorth, Marianne (2017). Med nanopartikler inn i fremtidens tannbehandling. Full text in Research Archive
• Hiorth, Marianne (2017). The potential of nanoparticles as a salivary substitute. Full text in Research Archive
• Hiorth, Marianne (2017). The NanoTeeth Project. Full text in Research Archive
• Hiorth, Marianne (2017). Development of polymer based nanospheres and polymer coated liposomes for drug delivery to the oral cavity. Full text in Research Archive
• Hiorth, Marianne (2016). Null hull. Full text in Research Archive
• Hiorth, Marianne; Pistone, Sara; Smistad, Gro & Goycoolea, Francisco (2016). Polymer-coated liposomes for protective functions of the teeth. Full text in Research Archive
• Hiorth, Marianne (2016). Can locally administered nanoparticles revolutionize the treatment of the oral cavity? Full text in Research Archive
• Hiorth, Marianne (2016). Nanotechnology for drug targeting/site specific drug delivery. Full text in Research Archive
• Nguyen, Sanko; Kur, Malgorzata Anna; Hiorth, Marianne & Smistad, Gro (2016). Formulation of pH-sensitive liposomes for caries prophylaxis. Full text in Research Archive
• Pistone, Sara; Goycoolea, Francisco; Smistad, Gro & Hiorth, Marianne (2016). Polymer coated liposomes intended for protective functions of the teeth. Full text in Research Archive
• Hiorth, Marianne (2016). Nanoparticles – The future for better oral health? Full text in Research Archive
• Nguyen, Sanko; Sediqi, Nadia; Smistad, Gro & Hiorth, Marianne (2016). Preparation and characterization of fluoride loaded polymeric nanoparticles for dental delivery. Full text in Research Archive
• Pistone, Sara; Qoragllu, Dafina; Smistad, Gro & Hiorth, Marianne (2015). Development of alginate nanoparticles as drug carriers for teeth ailments. Full text in Research Archive
• Pistone, Sara; Qoragllu, Dafina; Smistad, Gro & Hiorth, Marianne (2015). Development of an alternative method for the preparation of alginate nanoparticles by self-assembly. Full text in Research Archive
• Hiorth, Marianne (2015). Null hull med nanoteknologi. Full text in Research Archive
• Hiorth, Marianne (2015). Jakten på fremtidens nanomedisiner. Full text in Research Archive
• Hiorth, Marianne; Adamczak, Malgorzata Iwona; Nguyen, Sanko; Pistone, Sara; Sediqi, Nadia & Smistad, Gro (2015). Development of chitosan based nanoparticles for drug delivery to the teeth. Full text in Research Archive
• Hiorth, Marianne (2015). Jakten på fremtidens nanopartikler. Full text in Research Archive
• Hiorth, Marianne (2015). Bruk av nanopartikler i (fremtidens) legemidler. Full text in Research Archive
• Hiorth, Marianne (2015). Advanced drug delivery systems based on bioadhesion/mucoadhesion for local treatment of the oral cavity. Full text in Research Archive
• Hiorth, Marianne (2015). The Magic bullet - Nanopartikler i fremtidens legemidler. Full text in Research Archive
• Nguyen, Sanko; Pistone, Sara; Claudio, Cavalli; Smistad, Gro & Hiorth, Marianne (2015). Effect of ionic strength on the formation of fluoride loaded pectin nanoparticles for dental delivery. Full text in Research Archive
• Adamczak, Malgorzata Iwona; Hagesæther, Ellen; Hiorth, Marianne; Martinsen, Ørjan Grøttem; Sediqi, Nadia & Smistad, Gro (2015). Chitosan-based nanoparticles and chitosan-coated liposomes for drug delivery to the oral cavity. Full text in Research Archive
• Che, Loan Trinh; Kjøniksen, Anna-Lena; Lambermont-Thijs, Hanneke M. L.; Hoogenboom, Richard; Schubert, Ulrich S. & Hiorth, Marianne (2015). Complex Temperature and Concentration – dependent Self-assembly of Poly(2-oxazoline) Block Copolymers. Full text in Research Archive
• Pistone, Sara; Cavalli, Claudio; Smistad, Gro & Hiorth, Marianne (2014). Formulation of nanoparticles for protective functions of the teeth. Full text in Research Archive
• Yip, Wai Lam; Jonassen, Helene; Kjøniksen, Anna-Lena & Hiorth, Marianne (2013). Preparation of chitosan nanoparticles – a multivariate approach. Full text in Research Archive
• Jonassen, Helene; Kjøniksen, Anna-Lena & Hiorth, Marianne (2013). Polysaccharide-based Nanoparticles as a Drug Delivery System - Preparation and Physico-chemial Characterization. Full text in Research Archive
• Klemetsrud, Therese; Hiorth, Marianne; Kjøniksen, Anna-Lena & Smistad, Gro (2013). Liposomal complexes that changes around body temperature. Full text in Research Archive
• Klemetsrud, Therese; Kjøniksen, Anna-Lena; Hiorth, Marianne & Smistad, Gro (2012). Studies on pectin coated liposomes and their interaction with mucin. Full text in Research Archive
• Jonassen, Helene; Kjøniksen, Anna-Lena & Hiorth, Marianne (2012). Polysakkarid-baserte nanopartikler som legemiddelform. Full text in Research Archive

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