alexa Chitosan-sodium alginate nanoparticles as submicroscopic reservoirs for ocular delivery: formulation, optimisation and in vitro characterisation.
Pharmaceutical Sciences

Pharmaceutical Sciences

Clinical Pharmacology & Biopharmaceutics

Author(s): Motwani SK, Chopra S, Talegaonkar S, Kohli K, Ahmad FJ,

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Abstract Management of extraocular disease is mainly limited by the inability to provide long-term extraocular drug delivery without avoiding the systemic drug exposure and/or affecting the intraocular structures and poor availability of drugs, which may be overcome by prolonging the contact time with the ocular surface, for instance with bioadhesive polymers. In the present study, mucoadhesive chitosan (CS)-sodium alginate (ALG) nanoparticles were investigated as a new vehicle for the prolonged topical ophthalmic delivery of antibiotic, gatifloxacin. A modified coacervation or ionotropic gelation method was used to produce gatifloxacin-loaded submicroscopic nanoreservoir systems. It was optimised using design of experiments by employing a 3-factor, 3-level Box-Behnken statistical design. Independent variables studied were the amount of the bioadhesive polymers: CS, ALG and the amount of drug in the formulation. The dependent variables were the particle size, zetapotential, encapsulation efficiency and burst release. Response surface plots were drawn, statistical validity of the polynomials was established and optimised formulations were selected by feasibility and grid search. Nanoparticles were characterised by FT-IR, DSC, TEM and atomic force microscopy. Drug content, encapsulation efficiency and particle properties such as size, size distribution (polydispersity index) and zetapotential were determined. The designed nanoparticles have average particle size from 205 to 572 nm (polydispersity from 0.325 to 0.489) and zetapotential from 17.6 to 47.8 mV. Nanoparticles revealed a fast release during the first hour followed by a more gradual drug release during a 24-h period following a non-Fickian diffusion process. Box-Behnken experimental design thus facilitated the optimisation of mucoadhesive nanoparticulate carrier systems for prolonged ocular delivery of the drug. This article was published in Eur J Pharm Biopharm and referenced in Clinical Pharmacology & Biopharmaceutics

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