Ciprofloxacin-loaded dissolving polymeric microneedles as a potential therapeutic for the treatment of S. aureus skin infections.

Abstract

Microneedles have been widely studied for many topical and transdermal therapeutics due to their ability to painlessly puncture the skin, thereby bypassing the stratum corneum, the main skin barrier. In this study, ciprofloxacin (CIP) was loaded into dissolving polymeric microneedles prepared by a two-layer centrifugation method as a potential treatment of skin infections such as cellulitis. The polymers used were polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP). Two formulations were investigated, namely CIP_MN1, composed of 10 mg ciprofloxacin incorporated into a polymer matrix of PVA and PVP with a weight ratio of (9:1), and CIP_MN2, composed of 10 mg ciprofloxacin incorporated into PVA polymer. CIP_MN1 and CIP_MN2 showed a mean microneedle height of 188 and 179 µm, respectively. Since Parafilm has been proven as a model to examine the perforation of microneedles in skin, it was used to evaluate the ability of microneedles to perforate the skin. CIP_MN1 showed almost complete perforation of Parafilm, 190 pores, compared to CIP_MN2 which created only 85 pores in Parafilm, and therefore CIP_MN1 was used for subsequent studies. Examining CIP_MN1 on agarose gel as an in vitro model of human skin showed that the formula was able to fully perforate the agarose gel. Moreover, this formula showed significantly greater antimicrobial activity (p < 0.0001) compared to a free gel of ciprofloxacin against Staphylococcus aureus in an agarose gel-based model. This was evidenced by a zone of inhibition of 29 mm for the microneedle formulation of ciprofloxacin (CIP_MN1) compared to 2 mm for the free gel of ciprofloxacin. Furthermore, the CIP_MN1 showed complete dissolution in human skin after 60 min from application. Finally, the skin deposition of CIP_MN1 was investigated in ex vivo excised human skin. CIP_MN1 showed significantly more deposition of ciprofloxacin in deeper skin layers compared to the free gel of ciprofloxacin, and the released ciprofloxacin from the microneedles tends to migrate to deeper layers with time. Collectively, these results suggest that CIP_MN1 can be a potential delivery system for the treatment of S. aureus skin infections.