Preparation of controlled release ophthalmic drops, for glaucoma therapy using thermosensitive poly-N-isopropylacrylamide

In this study, controlled release ophthalmic agents for glaucoma therapy we re developed based on the thermosensitivity of poly-N-isopropylacrylamide ( PNIPAAm). The clear solution of PNIPAAm was known to undergo phase transiti on when the temperature was raised from the room temperature to about 32 de greesC. The drug was entrapped in the tangled polymer chains or encapsulate d within the crosslinked polymer hydrogel at room temperature, and released progressively after topical application (i.e., at a higher temperature). L inear PNIPAAm and crosslinked PNIAAm nanoparticles containing epinephrine w ere prepared. The drug release rate and cytotoxicity were investigated in v itro. Ophthalmic formulations based on either linear PNIPAAm or the mixture of linear PNIPAAm and crosslinked PNIPAAm nanoparticles were administered to rabbits and the intraocular pressure (IOP)lowering effect was evaluated. The decreased pressure response of the formulation based on linear PNIPAAm lasted six-fold longer than that of the conventional eye drop. Furthermore , for formulation based on the mixture of linear PNIPAAm and crosslinked na noparticles, the pressure-lowering effect lasted eight times longer. These results suggest the use of thermosensitive polymer solutions or hydrogels i s potential in controlled release antiglaucoma ophthalmic drugs. (C) 2001 E lsevier Science Ltd. All rights reserved.