Liposomes-in-hydrogel for topical drug delivery: Mechanical, kinetic, and biological insights
Benedetta Braido, Zora Rukavina, Øystein Grimstad, Silvia Franzè, Francesco Cilurzo, Željka Vanić, Nataša Škalko‐Basnet, Lisa Myrseth Hemmingsen
Abstract
Liposomes incorporated into chitosan hydrogels offer a promising drug delivery platform due to their physicochemical properties and biocompatibility. This study explores interactions between liposomes and hydrogel matrices, focusing on effects of polymer concentrations, textural properties, rheological behaviour, drug release, and biological effects, particularly biocompatibility. Mechanical and rheological evaluations showed that incorporation of liposomes into the hydrogel network enhanced the mechanical strength, as confirmed by texture analysis and evaluation of the rheological properties, whereas incorporation of curcumin-loaded liposomes led to a reduction in mechanical strength. All hydrogels exhibited shear-thinning behaviour, ensuring easy application while maintaining their structure afterward. Drug release analysis, using the Korsmeyer-Peppas model, revealed that liposomes followed a non-Fickian transport mechanism. Furthermore, incorporating them into hydrogels did not significantly alter the release rates, suggesting that liposomes primarily drive the controlled release. In contrast, non-formulated curcumin and curcumin in hydrogels alone showed slower, more complex release profiles. Despite this, the hydrogel plays a role in maintaining the applicability and skin retention, ensuring ease of application and prolonged skin contact. Curcumin demonstrated anti-oxidative activity comparable to vitamins C and E, effectively neutralizing free radicals. Moreover, biological evaluations confirmed biocompatibility of the liposome-hydrogel system in fibroblasts and significant anti-inflammatory activity in liposomal curcumin through nitric oxide modulation in LPS-stimulated macrophages. In conclusion, this hybrid system shows great potential for advanced therapeutic applications. The dual mechanism of liposomal encapsulation and hydrogel matrix enhances drug delivery and preserves biological activity, though careful evaluation of formulation-specific interactions remains crucial for designing suitable delivery systems.