Ana Cuk

• 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
• 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.

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• Cuk, Ana (2026). Formulation of injectable hydrogels for controlled release of local anesthetics in peripheral nerve blocks. Universitetet i Oslo. Full text in Research Archive Show summary

  Despite the rapidly growing comprehension of both physiology and pharmacology, pain treatment may still be invasive and generate cascades of events resulting in impaired health. An example is suppression of postoperative pain in surgical settings, which is routinely effectuated by repeated injections of local anesthetics. These demanding treatment protocols for patients and clinicians underscore the need for more user-friendly solutions. This work shows that injectable hydrogels can be well-suited carriers for local anesthetics, and therefore capable of reducing the dosage frequency. The hydrogels were prepared from stimuli-responsive polymers, materials that gel upon a certain stimulus such as ions or temperature. The gelling was initiated right before injection in case of ionic crosslinking, or after injection for thermoresponsive systems. Controlled release during several days, obtained in in vitro experiments, translated into a clear clinical effect in vivo. The peripheral nerve block simulation on a large animal model implied great potential for prospective administration in humans. The developed hydrogels could expand the use of local anesthetics to the management of chronic pain as well. In general, the hydrogel carriers could be suitable for any indication that would benefit from local drug delivery.

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