Study of Drug Release from Smart Mucoaahesive Nanoparticles Containing Nonsteroidal Anti Inflammatory Drugs for Use in Ophthalmic Formulations

Abstract

Introduction:The potential of polymeric nanoparticles as an ocular drug delivery system has been explored by a colloidal system consisting of an aqueous suspension of nanoparticles. These nanoparticles can be rapidly fabricated under extremely mild conditions with their ability to incorporate bioactive compounds. In present study the preparation and characterization of the novel cross-linked poly N-isopropylacrylamide-based micellar nanoparticles have been reported. Methods: Poly (N-isopropylacrylamide-acrylic acid-hydroxyethyl methacrylate) [Poly (NIPAM-AA-HEM)] and Poly (N-isopropylacrylamide-acrylic acid-vinyl pyrrolidone) [Poly (NIPAM-AA-VP)] copolymers were synthesized by free radical copolymerization of monomers in 1, 4-dioxane under N2 atmosphere. Triethylene glycol dimethacrylate (TEGDMA) was used as a novel cross-linking agent. For preparation of drug-loaded nanoparticles indomethacin got directly loaded into the hydrophobic core of micelles. Drug incorporation efficiency was expressed as drug content (DL %).In-vitro indomethacin release rate was tested using basket apparatus on a dissolution tester.Results: The chemical structures of cross-linked polymers were confirmed by FT-IR and 1H NMR spectroscopies. The PSA data represented that the particles has mean sizes between 200-470 nm. The maximum swelling ratio of hydrogel occurred at 10 min at 37 ?C and pH 1.0 and at 125 min at 20 ?C and pH 1.0. For all the formulations, the release rate was related to the drug-to-polymer ratio.For both P (NIPAAM-AA-HEM) and P (NIPAAM-AA-VP) preparations, a progressive increase of drug release rate was observed as a function of drug-polymer ratio.Conclusion: The prepared nanoparticles were stable in an aqueous solution and maintained their physical characteristics such as particle size and drug loading content during seven days of storage. It was demonstrated that the degree of in vitro indomethacin release from the PNIPAAM-based nanoparticles in pH 6.4 PBS buffer depended on the degree of drug loading.Key words: Indomethacin, poly N-isopropylacrylamide, micellar nanoparticles, in-vitro release