Effects of different N-trimethyl chitosans on in vitro/in vivo ofloxacin transcorneal permeation

Journal of Pharmaceutical Sciences
Giacomo Di ColoPatrizia Chetoni

Abstract

N-trimethyl chitosan (TMC) polymers differing in quaternization degree (QD) and molecular weight (MW) were prepared from two chitosans 90% deacetylated, one of higher MW (1460 kDa) (TMCH), the other of lower MW (580 kDa) (TMCL), by one (TMCH1, QD = 4%; TMCL1, QD = 3%), two (TMCH2, QD = 35%; TMCL2, QD = 46%), or three (TMCH3, QD = 90%; TMCL3, QD = 78%) reductive methylation steps. The derivatives were tested and compared for their ability to enhance the permeability of ofloxacin across rabbit corneal epithelium, reconstituted in vitro. TMC polymers of intermediate QD (TMCH2 and TMCL2), at the concentration of 0.001% w/v, produced significant permeability enhancements, independent of polymer MW. The enhancing effect did not increase when QD was increased (TMCH3 and TMCL3), while it was not significant with low QD values (TMCH1 and TMCL1). Such an effect was specific of chitosan derivatives, because fully quaternized DEAE-dextran (MeDD) was ineffective. The transcorneal permeability-enhancing property of TMCH2 and TMCL2, and the inefficacy of MeDD were confirmed by in vivo tests on rabbit eyes. However, unlike the in vitro experiments, the in vivo ones showed a stronger effect of the TMC having higher MW. TMCH2 produced antibiotic...Continue Reading

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