Oral Mucosal Permeabilization and Patient Acceptability of Chitosans

Objective:Chitosan is a naturally derived, biodegradeable and biocompatible biopolymer that has been proposed as a bioadhesive for oral mucosal drug delivery. The purpose of this study was 1) to compare the in-vitro permeabilizing effect of two chitosans, Chitosan H (Dainishiseika Colour & Chem. Mfg Co. Ltd, Japan) and Protasan CL213 (Pronova Biomedical, Norway), with that of a commonly used muco-adhesive, carbomer (Carbopol®974, Goodrich, USA) as a control and 2) to investigate the persistence and acceptability of these mucoadhesives in vivo. Methods:3H-hydrocortisone (HC), a topical oral anti-inflammatory agent to which oral mucosa is relatively impermeable, was incorporated into gels prepared with the three polymers. Porcine buccal mucosa was mounted in perfusion chambers, formulations applied for one hour and flux of HC and distribution in the tissue determined by horizontal sectioning and counting. Green food dye was incorporated into prepared unlabelled gels and applied blind to healthy buccal mucosa of 15 volunteers. The area of gels persisting on the surface for up to 6hrs was quantified from digital images. Subjects rated the acceptability of the gels on an ordinal scale in terms of 4 parameters. Results:flux of HC was greatest in the Chitosan-H but this was not significant; the amount penetrating to the deeper epithelium and connective tissue at 4 and 8 hours was significantly greater for Chitosan-H gel (p<0.05 ANOVA). Protasan CL213 and Chitosan-H persisted on the mucosa for significantly greater periods (p<0.05 ANOVA) than the carbomer. The acceptability ratings were not significantly different except for taste (?pleasant?/?not pleasant?) where Chitosan-H was considered significantly (p=0.019; Kruskal-Wallis ANOVA for Ranks) more pleasant than carbomer or Protasan. Conclusions:these findings suggest that the persistence, acceptability and permeabilization of chitosan gels make them important candidates for drug delivery across oral mucosa. (Supported by NIH Grant R21 DE13778)