High pH tolerance of a chitosan-PAA nanosuspension for ophthalmic delivery of pilocarpine.

In this paper, nanoparticles composed of chitosan (CS) and poly(acrylic acid) (PAA) were prepared by template polymerization for use as ophthalmic drug carrier. Before the polymerization, hydrogen peroxide was used to cut down the molecular weight of chitosan to improve its solubility and tolerance of pH values in the physiological condition. We found that, as the hydrogen peroxide concentration increased up to 2 M, the reaction temperature was kept at 60 degrees C and depolymerization for 2 h, the molecular weight of chitosan was cut down to 4.1 x 10(4) and its pH tolerance was increased up to 7.1. The modified chitosan (MCS) is expected to tolerate in neutral condition without any precipitation. MCS-PAA nanoparticles for use as an ophthalmic drug carrier were successfully prepared using template polymerization of acrylic acid in the modified chitosan solution. The particle size of the nanoparticles was significantly affected by the pH value of the medium. Both in vitro and in vivo studies reveal that the prepared nanoparticles either modified or unmodified have the better ability in sustaining the release of pilocarpine than the simulated tear fluid and commercial eye drops.