Atopic dermatitis (AD) is a chronically relapsing eczematous skin disease characterised by frequent episodes of rashes, severe flares, and inflammation. Till date, there is no absolute therapy for the treatment of AD; however, topical corticosteroids (TCs) are the majorly prescribed class of drugs for the management of AD in both adults and children. Though, topical route is most preferable; however, limited penetration of therapeutics across the startum cornum (SC) is one of the major challenges for scientists. Therefore, the present study was attempted to fabricate a moderate-potency TC, betamethasone valerate (BMV), in the form of chitosan nanoparticles (CS-NPs) for optimum dermal targeting and improved penetration across the SC. To further improve the targeting efficiency of BMV and to potentiate its therapeutic efficacy, the fabricated BMV-CS-NPs were coated with hyaluronic acid (HA). The prepared NPs were characterised for particle size, zeta potential, polydispersity index (PDI), entrapment efficiency, loading capacity, crystallinity, thermal behaviour, morphology, in vitro release kinetics, drug permeation across the SC, and percentage of drug retained into various skin layers. Results showed that optimised HA-BMV-CS-NPs exhibited optimum physicochemical characteristics including finest particle size (< 300 ± 28 nm), higher zeta potential (+ 58 ± 8 mV), and high entrapment efficiency (86 ± 5.6%) and loading capacity (34 ± 7.2%). The in vitro release study revealed that HA-BMV-CS-NPs displayed Fickian diffusion-type mechanism of release in simulated skin surface (pH 5.5). Drug permeation efficiency of BMV was comparatively higher in case of BMV-CS-NPs; however, the amount of drug retained into the epidermis and the dermis was comparatively higher in case of HA-BMV-CS-NPs, compared to BMV-CS-NPs. Conclusively, we anticipate that HA-BMV-CS-NPs could be a promising nanodelivery system for efficient dermal targeting of BMV and improved anti-AD efficacy.
Keywords: Atopic dermatitis; Betamethasone valerate; Chitosan nanoparticles; Dermal targeting; Hyaluronic acid; Penetration across stratum corneum.