Abstract
Polymeric hydrogels are common dosage forms designed for the topical administration of antimicrobial drugs to treat vaginal infections. One of the major advantages of using chitosan in these formulations is related to the intrinsic and broad antimicrobial activity exerted on bacteria and fungi by this natural polymer. Most vaginal yeast infections are caused by the pathogenic fungus Candida albicans. However, despite the anti-Candida activity towards and strains susceptibility to low molecular weight chitosan being documented, no information is available regarding the antimicrobial efficacy of mixed hydrogels in which chitosan is dispersed in a polymeric matrix. Therefore, the aim of the study is to evaluate the anti-Candida activity against eight different albicans and non-albicans strains of a mixed hydroxypropyl methylcellulose (HPMC)/chitosan hydrogel. Importantly, chitosan was dispersed in HPMC matrix either assembled in nanoparticles or in a monomolecular state to eventually correlate any variation in terms of rheological and mucoadhesive properties, as well as anti-Candida activity, with the chitosan form. Hydrogels containing 1% w/w chitosan, either as free polymer chain or assembled in nanoparticles, showed an improved mucoadhesiveness and an anti-Candida effect against all tested albicans and non-albicans strains. Overall, the results demonstrate the feasibility of preparing HPMC/CS mixed hydrogels intended for the prevention and treatment of Candida infections after vaginal administration.
Highlights
Chitosan has been extensively exploited to develop topical formulations for ocular, mucosal or skin applications thanks to its mucoadhesiveness and antimicrobial activity [1]
The results demonstrate the feasibility of preparing hydroxypropyl methylcellulose (HPMC)/CS mixed hydrogels intended for the prevention and treatment of Candida infections after vaginal administration
We propose here a formulation of a mixed hydrogel based on chitosan dispersed in a hydroxypropyl methylcellulose (HPMC) matrix loaded with metronidazole (MTZ) for vaginal application
Summary
Chitosan has been extensively exploited to develop topical formulations for ocular, mucosal or skin applications thanks to its mucoadhesiveness and antimicrobial activity [1]. Aimed at prolonging the residential time of the drug inside the vaginal cavity and to enhance the antibacterial or antifungal activity of the delivered drug, several vaginal dosage forms containing chitosan have been developed as films, tablets, inserts, hydrogels, and more recently, liposomes [2,3,4,5,6,7]. Among all these formulations, hydrogels are still the most used, allowing easy and precise administration and being largely versatile [8]. Cellulose derivatives, carboxypolymethylene and chitosan have been investigated to improve the contact of the formulation with the vaginal mucosa and to reduce the dilution and clearance of the hydrogels by the vaginal fluids [10]
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