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Preparation and Evaluation of N-Trimethyl Chitosan Nanoparticles of Flurbiprofen for Ocular Delivery.

Current Eye Research 2019 January 12
PURPOSE: A major challenge in ocular therapeutics is poor bioavailability of drug, 1% or even less of the instilled dose is absorbed and frequent administration of conventional products leads to poor adherence to therapy. Hence the present study is to synthesize N-trimethyl chitosan (TMC), a water-soluble chitosan derivative and to prepare flurbiprofen (FLU):hydroxyl propyl-β-cyclodextrin (HP-β-CD) complex loaded nanoparticles for treatment of bacterial conjunctivitis which aims to increase the residence time in ocular tissue thus enhancing patient compliance and improved efficacy.

METHODS: TMC was synthesized and characterized by 1 H NMR and FT-IR. TMC and chitosan (CS) nanoparticles containing inclusion complex were prepared by ionic gelation using sodium tripolyphosphate (TPP). The nanoparticles thus obtained were evaluated for particle size, zeta potential, drug entrapment, in-vitro release, in-vitro mucoadhesion and TEM for morphology and irritation potential was evaluated by the HET-CAM technique.

RESULTS: N-methyl quaternization of CS was confirmed by 1 H NMR. The particle size and zeta potential of the TMC nanoparticles were found to be 201 ± 1.55 nm and +13.9 ± 1.697 mV and that of CS nanoparticles were 361.2 ± 1.55 nm and +10.9 ± 0.424 mV respectively. The entrapment of FLU- HP-β-CD inclusion complex in polymeric nanoparticles was found to be 10.91 ± 1.541%. The observed in-vitro release profile of TMC nanoparticles indicated characteristic burst release followed by delayed release. HET-CAM studies demonstrated the ocular safety of TMC nanoparticles.

CONCLUSION: The developed TMC nanoparticles offered prolonged release potential for transmucosal ocular delivery of hydrophobic flurbiprofen.

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