Desirability function approach for development of a thermosensitive and bioadhesive nanotransfersome–hydrogel hybrid system for enhanced skin bioavailability and antibacterial activity of cephalexin

Abstract

Cellulitis is a common bacterial infection of the skin and soft tissues immediately beneath the skin. Despite the successful use of antibiotics in the treatment of infectious diseases, bacterial infections continue to impose significant global health challenges because of the rapid emergence of antibiotic resistance. The aim of this work was to develop an in situ hydrogel forming system containing highly permeable cephalexin-loaded nanotransfersomes (NTs), suitable for antibacterial drug delivery. Response surface design was applied for the optimization of NTs. Cephalexin NTs were prepared using thin-film hydration method and then embedded into a 3D hydrogel network. The in vitro antibacterial activity of the optimized NTs was assayed against indicator bacteria of Staphylococcus aureus (S. aureus). The drug permeation was evaluated using an ex vivo rat skin model. The in vivo efficacy of the cephalexin NT hydrogel was also determined against rat skin infection. The resulting data verified the formation of NTs, the size of which was approximately 192 nm. The cephalexin NTs exhibited higher antibacterial activity against S. aureus as compared to the untreated drug. The NT hydrogel improved drug penetration through the skin after 8 h. When applied on the rat skin for 10 days, the cephalexin NT hydrogel exhibited superior antibacterial activity with normal hair growth and skin appearance as compared with the plain drug hydrogel. These findings suggest that the cephalexin NT–hydrogel system can serve as a valuable drug delivery platform against bacterial infections.