Title : Development of metronidazole nanogels based on prosopisylated chitosan to treat vaginal candidiasis

Introduction: Vulvovaginal candidiasis (VVC) is an infection associated with diminished quality of life of many women, considerable morbidity and high and escalating healthcare cost to the society. The use of conventional vaginal therapies is limited by several problems.  There is need for better methods and agents to improve VVC treatment. Biopolymer-based nanomedicine could be employed to confer anticandidal activity on antibiotics such as metronidazole (MTZ), which do not possess anticandidal activity. This way, the formulation can be used for simultaneous treatment of vaginal co-infections.

Methods:  A recently patented green biopolymer (Prosopis africana gum, PG) was complexed with rational blends of chitosan (CS), a conventional cationic polysaccharide, with or without a cross-linker, sodium tripolyphosphate (TPP), via ionotropic gelation and the polyelectrolyte nanoparticles (prosopisylated chitosan nanoparticles) obtained were characterized using Fourier transform infra-red (FT-IR) spectroscopy, scanning electron microscopy and photon correlation spectroscopy. Prosopisylated chitosan nanoparticles were transformed into nanogels by dispersion in Hypromellose, incorporating MTZ. The nanogels were evaluated for physicochemical properties and in vitro anticandidal activity against Candida albicans and compared with unformulated and hydrogels by agar well diffusion technique.

Results: Prosopisylated chitosan nanoparticles were nanomeric complex dispersions with irregular polydispersed particles. FT-IR results confirmed the compatibility of MTZ and excipients used in the formulations. The vaginal MTZ-loaded nanogels had optimal pH within the vaginal region and exhibited improved inhibition zone diameter (IZD) against Candida albicans compared with the hydrogel. The hydrogel formulation containing Hypromellose, CS, PG and MTZ showed a mean IZD of 15.3 mm whereas its nanogel counterpart containing prosopisylated chitosan nanoparticles without a cross-linker (TPP) showed a mean IZD of 18.7 mm. MTZ alone showed no anticandidal activity whereas the MTZ-loaded nanogel formulation containing prosopisylated chitosan nanoparticles and a cross-linker (TPP) gave a mean IZD of 16.7 mm. Overall results indicated that MTZ-loaded nanogels formulated with prosopisylated chitosan nanoparticles with or without TPP exhibited potent anticandidal activity, attributable to the presence of the excipients.

Conclusion: Metronidazole-loaded nanogels formulated with TPP-cross-linked or uncross-linked prosopisylated chitosan nanoparticles is a promising strategy for treatment of VVC with high in vitro anticandidal activity, which could offer improved efficacy in vaginal bacterial and fungal co-infections treatment. Further stability, safety and in vivo studies on the nanogels are needed for formulation development.

Franklin Chimaobi Kenechukwu is a Professor and Head of the Department of Pharmaceutics at the University of Nigeria Nsukka (UNN), Nigeria. He joined the Drug Delivery and Nanomedicines Research group of the Department of Pharmaceutics, UNN in 2010. He earned a PhD at UNN and has won several travel and research grants and has done Postdoc in Brazil. He has published >100 scientific review and research articles and has made several presentations in conferences, symposia, seminars and workshops across the globe. He carries out research in the fields of drug delivery, pharmaceutical nanoscience, excipients development, infectious diseases and antimicrobial chemotherapy.