Corticosteroid-loaded chitosan-based in-situ forming gel combined with microneedle technology for improvement of burn eschar wound healing

Burn is one of the most common skin injuries and accounts for 300,000 deaths annually. Debridement and antibiotic therapy are major burn treatments, however, as debridement is not always possible and many drugs have poor penetration into necrotic tissue, permeation enhancement is acquired. Another challenge is the short duration of topically applied drugs. This study aims to address both problems by combining in-situ forming gels and microneedles. A chitosan-based in-situ forming gel of hydrocortisone was applied to human burn eschar using microneedles. The formulation was optimized using Design-Expert software. Formulation characterization was done in terms of gelling time and temperature, thermal analysis, release phenomenon, rheology, texture analysis, and stability. Finally, animal studies on mice burn wound treatment were conducted. Results showed that optimized formulation controlled the drug release, and wherever microneedle was used, drug permeation and flux increased (P-value < 0.05). In all ex-vivo and in-vivo stages, gel plus microneedle (length of 1.5 mm and application mode of 2) produced the best results concerning increased flux and faster recovery of burn eschar. In conclusion, the in-situ forming gel with appropriate texture, quality, and stability in combination with microneedle can be a good candidate for the controlled release of drugs in third-degree burn eschars.