Abstract
The present study aimed to develop lipase-sensitive nanoparticles-based hydrogel for topical delivery of fusidic acid (FA) against wound infection. Lipase sensitive nanosystem for fusidic acid delivery was formulated using poly (є-caprolactone) through the nanoprecipitation technique. Optimization, characterization and in vitro and in vivo studies were conducted. The optimized formulation had a particle size of approximately 225 nm and zeta potential −16 mV with an entrapment efficiency of 87%. Further FA nanoparticles (FA-NPs) were incorporated in carbopol hydrogel for drug delivery. FA-NPs and the hydrogel resulted in a 2-4-fold increase in its antibacterial activity as compared with FA solution and marketed cream. In vitro release studies were performed at different pH condition such as 5.5 (pH of normal skin), 6.5 (wound site pH) and 7.4 (physiological pH) in the presence lipase enzyme which showed a site-specific delivery of FA. In vitro permeation study of FA-NPs showed less permeation and higher retention in skin layers in comparison to FA-marketed cream and FA based hydrogel. Assessment of in vivo potential was evaluated in an MRSA-induced wound infection model and certain parameters associated with healing of wound infection were determined such as wound contraction, bacterial load, morphological and histopathological examination of wounds. Group treated with FA-NPs hydrogel have higher rate of wound contraction and a drastic decrease in bacterial count along with rapid and fast reepithelization resulting in improved healing of the wound. These results showed a unique on-demand and site-specific release of FA at the wound site by providing a moist environment and preventing bacterial infection. Based on the observed enhanced antibacterial and wound healing benefits, FA-NPs hydrogel formulation may be used as an alternative to commercial cream, especially in MRSA infected wounds.
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