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J Control Release. 2007 Jul 31;120(3):186-94. Epub 2007 May 17.

Poly(N-isopropylacrylamide)-chitosan as thermosensitive in situ gel-forming system for ocular drug delivery.

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College of Pharmacy, China Pharmaceutical University, Nanjing, PR China.


A novel copolymer, poly(N-isopropylacrylamide)-chitosan (PNIPAAm-CS), was investigated for its thermosensitive in situ gel-forming properties and potential utilization for ocular drug delivery. The thermal sensitivity and low critical solution temperature (LCST) were determined by the cloud point method. PNIPAAm-CS had a LCST of 32 degrees C, which is close to the surface temperature of the eye. The in vivo ocular pharmacokinetics of timolol maleate in PNIPAAm-CS solution were evaluated and compared to that in conventional eye drop solution by using rabbits according to the microdialysis method. The C(max) of timolol maleate in aqueous fluid for the PNIPAAm-CS solution was 11.2 microg/ml, which is two-fold higher than that of the conventional eye drop, along with greater AUC. Furthermore, the PNIPAAm-CS gel-forming solution of timolol maleate had a stronger capacity to reduce the intra-ocular pressure (IOP) than that of the conventional eye drop of same concentration over a period of 12 h. In addition, the MTT assay showed that there is little cytotoxicity of PNIPAAm-CS at concentration range of 0.5-400 microg/ml. These results suggest that PNIPAAm-CS is a potential thermosensitive in situ gel-forming material for ocular drug delivery, and it may improve the bio-availability, efficacy, and compliance of some eye drugs.

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