Reshaping Antibiotic Delivery: Chitosan‐based Polymeric Hydrogel for Transdermal Treatment of Drug Resistant Bacteria

The aim of the present study was to formulate and assess the antibacterial efficacy of a transdermal chitosan based polymeric hydrogel for transdermal treatment of bacterial resistance strains. Utilizing the micro-emulsion method and the Box-Behnken design model, imipenem-cilastatin (IMI-CIL) loaded nanostructured lipid carriers (NLCs) were fabricated and optimized, employing Compritol 888 ATO as the lipid core and Tween 80 as the stabilizer. The optimized nanoformulation underwent a comprehensive evaluation encompassing parameters such as particle diameter, zeta potential, surface morphology, entrapment efficiency, crystallinity, and molecular interaction. The optimized nanoparticles displayed a mean particle size of 129 nm, a zeta potential of -19.8 mV, and a polydispersity index (PDI) of 0.286. Detailed investigations into crystallinity and Fourier transform infrared (FTIR) analysis did not reveal any indications of molecular interaction. Both the IMI-CIL loaded NLCs and the hydrogel exhibited sustained in-vitro drug release. Moreover, the hydrogel, enriched with permeation enhancers, demonstrated a remarkable 15.77-fold increase in drug permeation. Furthermore, the IMI-CIL loaded NLCs exhibited significantly elevated antibacterial activity when juxtaposed with IMI-CIL solution, which demonstrated minimal activity against non-resistant bacterial species and lacked activity against resistant isolates. In summary, the IMI-CIL loaded NLCs hydrogel formulation assumes a pivotal role in bestowing sustained drug release and augmenting the antibacterial efficacy of carbapenem antibiotics. This holds promise as a potential solution to combat drug-resistant bacterial infections.