Thermosensitive in-situ forming gels for ophthalmic delivery of tea polyphenols

Abstract

This study aimed to develop a thermosensitive in situ gelling vehicle containing tea polyphenols (TPs) for ophthalmic delivery. Based on the different experiments of appropriate gel strength and gelling capacity under physiological conditions, the optimized concentrations of poloxamer 407/poloxamer 188 and carbopol 940 in the formulation were established to be 25% (w/v)/5% (w/v) and 0.1% (w/v), respectively. The combined solutions could be easily dropped as a fluid into the eye and further converted to gels under physiological conditions. Furthermore, using rabbit cornea, the effects of various formulation factors on the permeation of TPs were investigated both in vitro and in vivo. According to the outcome of transcorneal penetration experiment through the excised rabbit cornea in vitro, the formulation of F4 including 0.1% Azone showed the highest apparent permeability coefficient (Papp). Meanwhile, the result of ocular pharmacokinetic studies showed the area under the curve of the aqueous humor concentration-time profiles of TPs gel including 0.1% Azone was 2.83 times higher than that of TPs solution in the presence of Azone. These results demonstrate the in situ gel-forming delivery system may hold some promise in ocular delivery and can be a viable alternative to enhance the ocular bioavailability.