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Biodegradable in Situ Gelling Delivery Systems Containing Pilocarpine as New Antiglaucoma Formulations: Effect of a Mercaptoacetic acid/N-isopropylacrylamide Molar Ratio

Biodegradable in Situ Gelling Delivery Systems Containing Pilocarpine as New Antiglaucoma Formulations: Effect of a Mercaptoacetic acid/N-isopropylacrylamide Molar Ratio

Jui-Yang Lai

Drug Des Devel Ther. 2013 Oct 24;7:1273-85.

PMID: 24187486

Abstract:

Ocular drug delivery is one of the most commonly used treatment modalities in the management of glaucoma. We have recently proposed the use of gelatin and poly(N-isopropylacrylamide) (PNIPAAm) graft copolymers as biodegradable in situ forming delivery systems for the intracameral administration of antiglaucoma medications. In this study, we further investigated the influence of carrier characteristics on drug delivery performance. The carboxyl-terminated PNIPAAm samples with different molecular weights were synthesized by varying the molar ratio of mercaptoacetic acid (MAA)/N-isopropylacrylamide (NIPAAm) from 0.05 to 1.25, and were determined by end-group titration. The preparation of gelatin-g-PNIPAAm (GN) copolymers from these thermoresponsive polymers was achieved using carbodiimide chemistry. Our results showed that the carboxylic end-capped PNIPAAm of high molecular weight may lead to the lower thermal phase transition temperature and slower degradation rate of GN vehicles than its low molecular weight counterparts. With a decreasing MAA/NIPAAm molar ratio, the drug encapsulation efficiency of copolymers was increased due to fast temperature-triggered capture of pilocarpine nitrate. The degradation of the gelatin network could greatly affect the drug release profiles. All of the GN copolymeric carriers demonstrated good corneal endothelial cell and tissue compatibility. It is concluded that different types of GN-based delivery systems exhibit noticeably distinct intraocular pressure-lowering effect and miosis action, thereby reflecting the potential value of a MAA/NIPAAm molar ratio in the development of new antiglaucoma formulations.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
LS74671	Poly(N-isopropylacrylamide), carboxylic acid terminated			Price

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