Multilayer Films Based on Chitosan/Pectin Polyelectrolyte Complexes as Novel Platforms for Buccal Administration of Clotrimazole

Abstract

Buccal films are recognized as easily applicable, microbiologically stable drug dosage forms with good retentivity at the mucosa intended for the therapy of oromucosal conditions, especially infectious diseases. Multilayer films composed of layers of oppositely charged polymers separated by ionically interacting polymeric chains creating polyelectrolyte complexes represent very interesting and relatively poorly explored area. We aimed to develop the antifungal multilayer systems composed of cationic chitosan and anionic pectin as potential platforms for controlled delivery of clotrimazole. The systems were pharmaceutically characterized with regard to inter alia their release kinetics under different pH conditions, physicomechanical, or mucoadhesion properties with using an animal model of the buccal mucosa. The antifungal activity against selected Candida sp. and potential cytotoxicity with regard to human gingival fibroblasts were also evaluated. Interactions between polyions were characterized with Fourier transform infrared spectroscopy. Different clotrimazole distribution in the films layers highly affected their in vitro dissolution profile. The designed films were recognized as intelligent pH-responsive systems with strong antifungal effect and satisfactory safety profile. As addition of chitosan resulted in the improved antifungal behavior of the drug, the potential utilization of the films in resistant cases of oral candidiasis might be worth of further exploration.

The Expanded Role of Chitosan in Localized Antimicrobial Therapy

“…Among commonly studied delivery systems, mucoadhesive buccal films gained attention due to their superior palatability. The antifungal multilayer system composed of cationic chitosan and anionic pectin was developed for controlled delivery of clotrimazole by Potas et al [340]. Chitosan improved the antifungal activity of the drug, indicating the system s potential in the treatment of resistant oral candidiasis.…”

Polyelectrolyte Multilayer Films as a Potential Buccal Platform for Drug Delivery

“…Buccal films have gained relevance as novel, convenient and patient-friendly formulations [8]. These formulations have been developed to release drugs locally for the treatment of fungal or bacterial infections [9][10][11][12]. Mucoadhesive films, in turn, provide intimate contact with buccal mucosa, which implies longer retention time and can therefore release drugs in a prolonged manner [13,14].…”

“…Multilayer films, which are usually prepared using a self-assembly technique, are an emerging field of drug delivery and a promising option to achieve the desired goals [9]. Typically, multilayer films are based on polyelectrolyte linkage between oppositely charged polymer molecules.…”

Pectin–Zeolite-Based Wound Dressings with Controlled Albumin Release

“…Based on our findings, loading pH alters (i) the electrostatic distribution of amphoteric BSA surface; (ii) protonation and deprotonation of -COOH groups of pectin [51]; (iii) the extent of interactions between Ca 2+ and BSA or pectin hydrogel [52]. The interactions between proteins and solid surfaces can be affected by the heterogeneity of the surface and molecular properties of the adsorbed molecules [53].…”

“…On the other hand, at pH 6.4, 100 mg BSA-containing films (A6.4-100, M6.4-100) gave the characteristic alpha-helical peaks for BSA, showing that the secondary structures are maintained. According to literature, the interaction between BSA and metal complexes often leads to a perturbation of the secondary structure of the protein [51], leading to a partial loss of alpha-helix conformation. Ca 2+ ions can bind BSA at the pH range 6.5-8.5 for both mixing and adsorption films that have 100 mg BSA (A6.4-100, M6.4-100).…”