Formulation and characterization of a topical treatment based on chitosan methacrylate and magnetoliposomes to enhance cutaneous drug delivery

Abstract

The skin is the body's first line of defense against external chemical, biological, and physical agents. Its composition poses challenges for the penetration of pathogens as well as drugs or active components intended for topical administration. Currently, liposomes are used to enhance the permeation of such drugs through the lipid membranes of tissues. This encapsulation also improves the biocompatibility of the treatment and allows for controlled release based on their charges. Additionally, surface-functionalized magnetic nanoparticles have been employed to target drug delivery. The use of pH- and temperature-sensitive linkers is also a strategy currently used to exert greater control over drug release at the desired site. In this study, a topical treatment formulation based on methacrylated chitosan hydrogels and magnetoliposomes was developed to enhance the penetration of drugs with limited permeability. Magnetite nanoparticles functionalized with PEG polymer, AEDP or v50 linkers, and the drug DOX were synthesized, resulting in three nanoconjugates: MNPs-PEG-DOX, MNPs-PEG-AEDP-DOX, and MNPs-PEG-V50-DOX. These nanoconjugates were encapsulated in soy lecithin liposomes through bilayer hydration. Subsequently, they were dispersed in a methacrylated chitosan hydrogel to achieve controlled and sustained release of the nanocarriers into the tissue. The successful synthesis of the entire treatment was analyzed through physicochemical and microscopic characterizations. Magnetoliposomes of 143 ± 20 nm encapsulating nanoparticles of 12.5 ± 4.4 nm were obtained. Hemocompatibility assays showed that none of the components were hemolytic or induced greater platelet aggregation than the PBS control. The final treatments containing MNPs-PEG-AEDP-DOX and MNPs-PEGV50-DOX resulted in a 50% decrease in viability of HaCat keratinocyte cells. In vitro diffusion and permeation assays demonstrated that the administration of nanocarriers via a hydrogel enables controlled and sustained release over time. Furthermore, the encapsulated nanoparticles exhibited improved permeation in porcine skin under physiological conditions. These results indicate that the developed formulation holds promising potential as a drug delivery system for cutaneous administration.