Effect of Sperminated Pullulans on Drug Permeation through Isolated Rabbit Cornea and Determination of Ocular Irritation

Abstract

The aim of this study was to investigate the effect of two sperminated pullulans (SP) with a different number of amino groups (SP-L, amino group content 0.124 mmol/g polymer; and SP-H, amino group content 0.578 mmol/g polymer) on the permeation of drugs through isolated rabbit corneas. Determination of corneal hydration levels and Draize eye tests were performed to assess the safety of SP both in vitro and in vivo. For 0.2% (w/v) SP-L and 0.2% (w/v) SP-H, the enhancement ratios (ERs) with dexamethasone of 1.34 and 1.42, respectively, were not statistically significant. For ofloxacin, tobramycin and sodium fluorescein, the ERs with 0.2% SP-L were 1.37, 2.02 and 2.12, respectively, and with 0.2% SP-H the ERs were 1.84, 4.69 and 6.87, respectively; these ERs were all statistically significant. Enhancement increased with increasing amino group content of the SP. The improved transcorneal drug absorption via the paracellular route indicated opening of the tight junctions in the corneal epithelium. Irritation tests indicated that 0.2% SP-L and 0.2% SP-H did not damage the corneal tissues.

Screening of chemical linkers for development of pullulan bioconjugates for intravitreal ocular applications

“…Due to its biocompatibility, multi-valency, solubility and biodegradability, pullulan has been widely used to produce nanoparticles or polymeric conjugates for systemic drug administration (Shingel, 2004;Singh et al, 2017). In ocular drug delivery, pullulan has been used only as mucoadhesive excipient for topical application (Pevet et al, 2011;Shingel, 2004;Singh et al, 2017), while its application for controlled or targeted intravitreal delivery is unexplored (Garhwal et al, 2012;Yu et al, 2010).…”