Chitosan-hydroxypropyl methylcellulose tioconazole films: A promising alternative dosage form for the treatment of vaginal candidiasis

Abstract

Vaginal candidiasis is considered a frequent opportunistic mucosal infection and the second most common cause of vaginitis after bacterial vaginosis. In this work, different vaginal films based on chitosan, hydroxypropyl methylcellulose and blends of these polymers containing tioconazole, were developed and thoroughly characterized to improve the conventional therapeutics of vaginal candidiasis. Mechanical properties, swelling, adhesiveness, morphology, antifungal activity, hemocompatibility and cytotoxicity were evaluated. The drug solid state in the films was analyzed by thermal and X-ray diffraction analysis. Films showed homogeneous surfaces and presented similar mechanical properties and adhesiveness. Time-kill studies displayed that films were more active than both tioconazole pure drug and traditional tioconazole ovule against Candida albicans, which is probably related to the fact that tioconazole is in amorphous state inside the films. Although all formulations proved to be hemocompatible, films based only on chitosan exhibited a certain degree of cytotoxicity and therefore they should be avoided. The system based on chitosan-hydroxypropyl methylcellulose with 40% PEG 400 as plasticizer presented fast antimicrobial activity as well as the lowest swelling. Additionally, this formulation did not produce substantial hemolytic and cytotoxic effects, indicating that films based on chitosan-hydroxypropyl methylcellulose could be a promising alternative dosage form for the treatment of vaginal candidiasis.

Promising Drug Delivery Approaches to Treat Microbial Infections in the Vagina: A Recent Update

“…The authors explained that overhydration of the polymers can affect the adhesive strength due to the disentanglement of the polymers at the interface. Although the film with 1% w/v chitosan, 5% w/w PEG 400, and without HPMC showed the highest swelling ability, it is insufficient to affect the adhesiveness, resulting in similar mucoadhesive strength of all the formulations being observed [96]. Mishra et al designed a clotrimazole mucoadhesive film based on different compositions of hydroxypropyl cellulose (HPC), sodium alginate, and different ratios of the plasticizers.…”

“…The authors explained that over-hydration of the polymers can affect the adhesive strength due to the disentanglement of the polymers at the interface. Although the film with 1% w/v chitosan, 5% w/w PEG 400, and without HPMC showed the highest swelling ability, it is insufficient to affect the adhesiveness, resulting in similar mucoadhesive strength in all the developed formulations [96]. Alternatively, Rençber et al used HPMC K100M and E50 to develop an in situ vaginal gel using poloxamer 407 (P407) and 188 (P188) containing clotrimazole for the treatment of vaginal candidiasis.…”

Design and Characterization of Chitosan Nanoformulations for the Delivery of Antifungal Agents

“…Hence, these systems present a promising strategy for local TIO or ECO delivery, which might be used to load films with these antifungal nanocapsules as a pharmaceutical dosage form suitable for the treatment of vaginal candidiasis. This promising film would combine the properties of the film [8] with the advantages associated with nanocapsules, such as the control of the drug release [50,51].…”

“…Azole agents have a common mechanism of action which is based on interfering with biosynthesis of ergosterol and thereby altering the normal functions of the cell membrane, causing cell death [4,5]. TIO (1-[2-[(2-chloro-3-thienyl)methoxyl]-2-(2,4-dichlorophenyl)ethyl]-1 H -imidazole, Figure 1A) and ECO (1-[2-[(4-chlorophenyl)methoxyl]-2-(2,4-dichlorophenyl)ethyl]-1 H -imidazole Figure 1B) are highly lipophilic antifungal drugs (log P values of 4.4 [6] and 5.61 [7], respectively) classified into class II (high permeability and low solubility) of the Biopharmaceutical Classification System [8].…”

“…These drugs have been found to be effective against C. albicans [8,9]; however, their low water solubility may affect their effective concentration in the target site (mucosa) and therefore their therapeutic action. To overcome these problems, different formulations based on cyclodextrins, films, and gels have been developed for the treatment of vaginal candidiasis [8,10,11,12]. Moreover, it has been reported that antifungal resistance continues growing, urging a need for the development of new bioactive compounds and new formulations of antifungals for treatments against Candida infections [4].…”