Gatifloxacin Nanoparticles for Ophthalmic Delivery Sanjay K. Motwani, Shruti Chopra, Farhan J. Ahmad * , Z. Iqbal, S. Talegaonkar and Roop K. Khar Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi-110062, India, Tel.: +91-11-26059688, Fax: +91-11-26059663 (*For Correspondence: farhanja_2000@yahoo.com) ABSTRACT Ocular efficacy of drugs being greatly influenced by the corneal contact time, the most promising approach to increase ocular bioavailability would be to increase pre- corneal residence time by using adequate drug delivery systems. Present research work aimed at developing the cationically modified PLGA nanoreservoir systems of Gatifloxacin for ocular delivery. A modified Emulsion- diffusion-evaporation technique was used to prepare PLGA nanoreservoir systems, stabilized by polyvinyl alcohol and chitosan. The prepared nanospheres were characterized for particle size and size distribution (polydispersity) by dynamic light scattering, zetapotential, drug content & encapsulation efficiency and in vitro drug release profile (phosphate buffer pH 7.4, 100 ml). Surface properties of the nanospheres were studied by TEM and AFM. The designed nanospheres have average particle size from 318-556 nm (polydispersity from 0.325-0.489) and zetapotential from 21-36 mV at pH 7.4. Keywords: gatifloxacin, PLGA, nanoparticles, ocular delivery. 1 INTRODUCTION Polymeric nanoparticles or submicroscopic colloidal carriers have been suggested to combine the ophthalmic prolonged action with the ease of the application of liquid eye drops [1]. Biodegradable colloidal nanoparticles of Poly (lactide-co-glycolide) (PLGA) have received considerable attention as a possible means of delivering drugs because of their favorable biocompatibility and easy resorbability through natural pathways [2]. Various methods reported for preparation of PLGA nanoparticles include: emulsion-evaporation [3], salting-out [4], nanoprecipitation [5], cross-flow filtration [6] or emulsion- diffusion [7]. However, improvements in the existing methods are still needed to overcome the difficulties in terms of obtaining reproducibility, particle size, and shape of nanospheres. With the problem of increasing resistance to fluoroquinolones amongst bacterial ocular isolates, Gatifloxacin has been suggested as a promising novel broad-spectrum antibacterial agent. However, given by intravenous infusion or oral route, it leads to adverse effects associated with gastrointestinal tract and CNS [8]. Hence, the objective of this study was to develop bioadhesive chitosan coated PLGA nanoreservoir systems of Gatifloxacin for local delivery with reduced dose of the drug, to avoid the systemic side effects and hence to improve the therapeutic index of drug. 2 EXPERIMENTAL 2.1 Materials [Poly (d,l-lactide-co-glycolide)] (PLGA, 75:25 lactide:glycolide), Purasorb–PDLG was received as a gift sample from PURAC Biochem, The Netherlands. The polymer Chitosan (CS) (Specifications: low molecular weight, viscosity of 1% w/v aqueous solution in 1% v/v acetic acid-130 cps, Deacetylation degree >80%) was a generous gift from India Sea Foods. Polyvinyl alcohol (PVA) was purchased from CDH Labs. Gatifloxacin was supplied by Lupin Labs Ltd., India. All other reagents and solvents used in the study were of analytical grade and used as received. 2.2 Preparation of Nanoparticles PLGA nanospheres were prepared by a modified Emulsion-Diffusion-Evaporation (EDE) technique [3]. Briefly; 100 mg of PLGA is dissolved in 10 ml of methylene chloride (organic phase) at room temperature. The organic phase is then added to an aqueous solution containing 20 mg gatifloxacin, PVA (0.25%, 0.50% or 1.0%) and chitosan (0.10%, 0.20% or 0.40%) in 10 ml of 2% v/v glacial acetic acid under stirring. The emulsion is stirred at room temperature for 1 h. followed by homogenization at 15,000 rpm for 10 min using Heidolph DIAX 900 homogeniser (Heidolph, Germany). To this emulsion, 20 ml of water is added under stirring resulting in nanoprecipitation and formation of chitosan-coated PLGA nanoreservoir systems of gatifloxacin. Stirring is continued on a water bath maintained at 40 0 C to remove organic solvent. Nanospheres were finally collected by centrifugation at 18,000 rpm for 30 min at 4 0 C (REMI, India). To study the possible effect of the viscosity of the chitosan solution on the particle size of chitosan-coated PLGA nanoparticles, different concentrations of the two hydrophilic polymers (CS and PVA), and their ratios were tried (from 1:0.625 to 1:10), which are presented in Table 1 with the observed particle size, polydispersity and zetapotential. NSTI-Nanotech 2007, www.nsti.org, ISBN 1420061836 Vol. 2, 2007 310