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

Int J Pharm. 2019 Feb 10:556:181-191. doi: 10.1016/j.ijpharm.2018.12.011. Epub 2018 Dec 12.

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.

Keywords: Antifungal activity; Cytotoxicity; Films; Mechanical properties; Vaginal candidiasis.

Publication types

  • Comparative Study

MeSH terms

  • Adhesiveness
  • Antifungal Agents / administration & dosage*
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology
  • Candida albicans / drug effects
  • Candidiasis, Vulvovaginal / drug therapy
  • Cell Line, Tumor
  • Chemistry, Pharmaceutical / methods
  • Chitosan / chemistry*
  • Drug Carriers / chemistry
  • Female
  • Humans
  • Hypromellose Derivatives / chemistry*
  • Imidazoles / administration & dosage*
  • Imidazoles / chemistry
  • Imidazoles / pharmacology
  • Plasticizers / chemistry
  • Polyethylene Glycols / chemistry
  • X-Ray Diffraction

Substances

  • Antifungal Agents
  • Drug Carriers
  • Imidazoles
  • Plasticizers
  • Hypromellose Derivatives
  • Polyethylene Glycols
  • Chitosan
  • polyethylene glycol 400
  • tioconazole