Chitosan nanoparticles embedded hydrogels as a novel nanomedicine based strategy for the treatment of vaginal infections

The use of chitosan as a mucoadhesive and antimicrobial biopolymer in topical formulations has been widely explored [1]. Particularly, chitosan-based hydrogels have been formulated for vaginal administration in order to prolong the residential time of the formulation in the vaginal cavity and to enhance the antibacterial or antifungal activity of the delivered drug [2]. In this field, a nanomedicine-based approach employing chitosan as a nanocarrier has been developing in recent year for the treatment of vaginal infections [3,4]. We propose here the formulation of a mixed hydrogel based on chitosan nanoparticles embedded inside a hydroxypropyl methylcellulose (HPMC) matrix for the vaginal delivery of metronidazole as an antimicrobial drug. HPMC hydrogels containing chitosan as a free polymer were also prepared as comparison. Firstly, chitosans with different molecular weights (Mw) and degree of acetylation (DD) were screened in acetate buffer at pH 4.5 in term of size and stability of the prepared nanoparticles. Then, chitosan with a low Mw (<50 kDa) and high DD (>90%) was chosen and the hydrogels containing 0.1%, 0.5% and 1% w/w of nanoparticles were prepared. The hydrogels were characterized in terms of their rheological behaviour and mucoadhesiveness. The presence of chitosan as free polymer or as nanoparticles did not markedly affect the strength of the hydrogel, but it slightly increased its mucoadhesive properties. The antimicrobial activity of the hydrogels was assessed in agar well diffusion method (AWDM) by testing the formulation containing 1% of chitosan (as free polymer or nanoparticles) loaded or unloaded with 0.75% w/w of metronidazole against three human clinical isolates of Candida spp. The growth inhibition area clearly indicated the crucial role exerted by chitosan in the formulation against Candida spp. Our results demonstrate the possibility of incorporating chitosan nanoparticles inside a polymeric hydrogel and its effectiveness as a promising formulation for the treatment of vaginal infections