In this study, controlled release ophthalmic agents for
glaucoma therapy were developed based on the thermosensitivity of
poly-N-isopropylacrylamide (
PNIPAAm). The clear
solution of
PNIPAAm was known to undergo phase transition when the temperature was raised from the room temperature to about 32 degrees C. The
drug was entrapped in the tangled
polymer chains or encapsulated within the crosslinked
polymer hydrogel at room temperature, and released progressively after topical application (i.e., at a higher temperature). Linear
PNIPAAm and crosslinked PNIAAm nanoparticles containing
epinephrine were prepared. The drug release rate and cytotoxicity were investigated in vitro. 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 nanoparticles, the pressure-lowering effect lasted eight times longer. These results suggest the use of thermosensitive
polymer solutions or
hydrogels is potential in controlled release antiglaucoma ophthalmic drugs.