Effect of chitosan and of N-carboxymethylchitosan on intraocular penetration of topically applied ofloxacin

Polysaccharides as Excipients for Ocular Topical Formulations

“…For this reason the effect of CMCh, a polyanionic Ch derivative soluble at this pH (Fig.3), on transcorneal drug absorption is of particular relevance. Although CMCh was found to behave as an intestinal absorption enhancer (Thanou et al, 2001) , it failed to significantly enhance corneal permeability, in fact, the drug levels produced in the aqueous by CMCh never exceeded the C max for the reference Exocin ® (Di Colo et al, 2004b). Then it appears that the polycationic nature of Ch is essential to its permeabilizing effect on the cornea.…”

“…More recently Ch solutions have been investigated for their ability to improve intraocular drug bioavailability, following topical administration, by enhancing corneal permeability. Although the ability of Ch to permeabilize nasal mucosa and intestinal epithelium has been known since 1994 Artursson et al, 1994) the permeabilizing effect of this polymer applied via eye drops on the cornea was demonstrated for the first time ten years later (Di Colo et al, 2004b). Unlike the intestinal and nasal epithelia, both made of a single layer of cells joined by tight junctions, the cornea is a stratified epithelium the cells of which also are joined by tight junctions.…”

“…Therefore, the ability of Ch to enhance the permeability of intestinal and nasal epithelia would not necessarily imply a similar effectiveness on the corneal epithelium. Instead of using the excised cornea, as in previous studies of the enhancement of corneal permeability to drugs, the permeabilizing effect of Ch was investigated in vivo (Di Colo et al, 2004b) . To this purpose, ofloxacin was instilled into the eyes of albino rabbits via isoviscous eye drops containing Ch hydrochloride (Ch-HCl), or N-carboxymethyl Ch (CMCh) (Muzzarelli et al, 1982), or poly(vinyl alcohol) (PVA), and the resulting pharmacokinetics in tear fluid and aqueous humor were determined (Di Colo et al, 2004b).…”

“…Instead of using the excised cornea, as in previous studies of the enhancement of corneal permeability to drugs, the permeabilizing effect of Ch was investigated in vivo (Di Colo et al, 2004b) . To this purpose, ofloxacin was instilled into the eyes of albino rabbits via isoviscous eye drops containing Ch hydrochloride (Ch-HCl), or N-carboxymethyl Ch (CMCh) (Muzzarelli et al, 1982), or poly(vinyl alcohol) (PVA), and the resulting pharmacokinetics in tear fluid and aqueous humor were determined (Di Colo et al, 2004b). CMCh, a polyanion at the physiological pH of the tear fluid (Fig.3), was tested to ascertain the relevance of the polycationic nature of Ch-HCl and because CMCh was claimed to behave as an intestinal absorption enhancer (Thanou et al, 2001).…”

“…Interestingly, however, the drug concentration in the aqueous vs. time data relative to CMCh pointed to zero-order transcorneal absorption kinetics. This observation prompted the hypothesis that CMCh might mediate a pseudosteady-state transcorneal transport, via polymer interactions with the drug and polymer adhesion to the corneal mucus (Di Colo et al, 2004b). Such a mucoadhesion could prolong the drug residence at the absorption site.…”