INTERNATIONAL JOURNAL OF SCIENTIFIC & TECHNOLOGY RESEARCH VOLUME 1, ISSUE 10, NOVEMBER 2012 ISSN 2277-8616 31 IJSTR©2012 www.ijstr.org Synthesis And Optimization of Streptomycin Loaded Chitosan-Alginate Nanoparticles Meenu Chopra, Pawan Kaur, Manju Bernela, Rajesh Thakur Abstract- Nanoformulation consisting of Streptomycin loaded chitosan-alginate nanoparticles were prepared using ionotropic-pregelation method and optimization was done in terms of polymer concentration, crosslinker concentration and stirring time. The optimal parameters were found to be Chitosan 0.75mg/ml, calcium chloride 1% (w/v) and stirring time 90 min. Polymer (chitosan and sodium-alginate) and crosslinker (calcium-chloride) at these concentrations had significant synergistic effect on particle size and % encapsulation efficiency. Increase in polymer and crosslinker concentration resulted in an increase in particle size. Encapsulation efficiency, first showed an increase followed by a decrease, on increasing the polymer concentration whereas it increased with an increase in cross linker concentration. The nanoformulation so formed showed particle size 328.4 nm & drug encapsulation 93.32%. Keywords: Streptomycin, Chitosan, Sodium alginate, nanoformulations, calcium chloride, ionotropic pregelation ———————————————————— 1 INTRODUCTION THE efficacy of many drugs is often limited by their potential to reach the site of therapeutic action due to various problems such as - poor bioavailability, in vivo stability, solubility, intestinal absorption, sustained and targeted delivery to site of action, therapeutic effectiveness; side effects, and fluctuations of drug concentration in plasma which either fall below the minimum effective concentrations or exceed the safe therapeutic concentrations . In most cases only a small amount of administered dose reaches the target site, while the majority of the drug distributes throughout the rest of the body in accordance with its physicochemical and biological properties [1]. Streptomycin is bactericidal antibiotic drug under aminoglycosides category and derived from Streptomyces griseus [2]. It is also used to control bacteria, fungi, and algae in crops [3]. It is known to have toxic effects causing nephrotoxicity and neuroparalysis [4]. Application of nanotechnology in drug delivery system has opened up new possibilities in sustained and targeted release of drugs [5]. Specifically designed tiny nanoparticles can reach less accessible sites in the body by escaping phagocytosis and entering tiny capillaries. Controlled release of the drug from the nanoformulations could maintain steadier levels of drug in bloodstream for longer durations. Sustained release of drug can be achieved by encapsulating the active ingredient in a polymer matrix such that drug find its way through the restrictive cavities in the matrix Thus, the dose and frequency of administration would be reduced [6-7]. Sodium-alginate and chitosan both are extensively used in encapsulation of drug for the purpose of sustained release. These are polysaccharide polymers, formed of repeating units (either mono- or di- saccharides) joined together by glycosidic bond [8]. Both polymers have the properties of an ideal carrier for drug delivery, such as biocompatibility, biodegradability, non-toxicity, and low cost [9]. Chitosan is a polycation component, which has amino groups [10] and sodium alginate has many anionic or cationic groups in the structure; therefore, they exhibit unique physical property by electrostatic interaction [11-12]. Many other antibiotic nanoformulations are reported such as Oral administration of ciprofloxacin containing sodium-alginate nanoparticles [13]; Sepia nanoparticles as a potential drug carrier for amoxicillin trihydrate. Sepia nanoparticles system has also been used as a model for carrying out in vitro drug release and stability studies in response to different drug and polymer ratios [14]. Sodium-alginate nanosphere containing ofloxacin were also formulated by using controlled gelation method in which the prepared nanoparticles were evaluated to assess the various parameters such as drug polymer ratio, drug content analysis, particle size analysis (SEM analysis), and in vitro drug release[15]. In the present work we encapsulated streptomycin into polymers to form nanoformulations and optimized its various parameters to enhance its encapsulation efficiency and to reduce the particle size which may be helpful in reducing its toxicity. 2 MATERIALS AND METHODS Chitosan and Streptomycin sulphate were procured from Hi media laboratories (P) Ltd. (Mumbai, India). Sodium-alginate and calcium chloride were procured from S.D. Fine Chemicals Ltd. (Mumbai, India). 2.1 Synthesis of chitosan-alginate nanoparticles Chitosan/alginate nanoparticle formulation is two step process based on ionotropic pre-gelation previously described [16] but modified according to ideal preparation. Calcium chloride solution (7.5ml) was added dropwise to sodium alginate solution (117.5ml, 0.0063% w/v) to induce gelation. It was stirred for 60 minutes and then 25 ml of chitosan solution was added dropwise along with constant stirring for 90 minutes. Drug was incorporated at the rate 1 mg/ml to sodium alginate solution in step one itself, before adding to calcium chloride for gelation. Nanoparticles were concentrated by centrifugation at 11,500 rpm for 40 min. Nanoparticles thus formed were analyzed for particle size. The optimized nanoparticles were frozen at -80 °C for 4 h followed by Lyophilization on freeze dryer (Alpha 2-4 LD plus, Martin Christ, Germany) for 24 h at - 90 °C at 0.0010 mbar using mannitol (1% w/v) as cryoprotectant. ———————————————— • Dr. Rajesh Thakur is Assistant Professor in Department of Bio & Nano Technology, Guru Jambheshwar University of Science & Technology, Hisar, Haryana, India, PH-01662-263514. E-mail: rthakur99@rediffmail.com .