Biotechnology and Bioprocess Engineering 16: 383-392 (2011) DOI 10.1007/s12257-010-0099-7 Synthesis of Low Molecular Weight Alginic Acid Nanoparticles through Persulfate Treatment as Effective Drug Delivery System to Manage Drug Resistant Bacteria Dipankar Ghosh, Arindam Pramanik, Narattam Sikdar, and Panchanan Pramanik Received: 29 March 2010 / Revised: 10 October 2010 / Accepted: 30 October 2010 © The Korean Society for Biotechnology and Bioengineering and Springer 2011 Abstract The purpose of this study was to prepare low molecular weight alginic acid (LMWA) nanoparticles by cation-induced, controlled gelification of depolymerized alginic acid for effective drug delivery to drug resistant bacteria. The depolymerization reaction was performed using potassium persulfate oxidation at an optimized condi- tion. The optimized conditions for depolymerization were anticipated to be 37 o C, pH 4, 2 days reaction time, and a 0.075 M concentration of potassium persulphate containing 0.001 M silver nitrate in the final reaction mixture. Gel permeation chromatography showed depolymerized alginic acid had an average molecular weight of 20.95 ± 0.49 kDa. Depolymerized alginic acid was also characterized for its structural integrity by X-ray diffraction, nuclear magnetic resonance, and Fourier transform spectroscopy. Depoly- merized alginic acid was used to prepare low molecular weight nanoparticles with a particle size of 54 ± 0.41 nm, and a zetapotential of −32.2 ± 3.91 mV. The nanoparicles were then subjected to tetracycline loading. In vitro drug loading and drug release efficiencies after 100 h were determined to be 66.56 ± 1.88 and 61.8 ±0.141%, respec- tively. Finally, the minimal inhibitory concentration and a putative mode of action for the tetracycline nanoparticles were determined using tetracycline resistant bacteria, Escherichia coli XL-1. Keywords: low molecular weight, alginic acid, drug delivery, minimal inhibitory concentration, drug resistant bacteria 1. Introduction Alginic acid is a well known anionic polysaccharide widely distributed in the cell wall of brown algae. It is a linear copolymer with homopolymeric blocks of (1-4)- linked β-D-mannuronate (M) and its C-5 epimer, α-L- guluronate (G) residues, covalently linked together in different sequences or blocks. The monomers can appear in homopolymeric blocks of consecutive G-residues (G-blocks), consecutive M-residues (M-blocks), alternating GM-blocks, or randomly organized blocks [1]. Keeping in mind their gelling ability, stabilizing properties, and high viscosity in aqueous solutions, alginates and their derivatives are widely used in the food, cosmetics and pharmaceutical industries as a drug carrier [2]. According to the literature, alginic acid based microcapsules, and nanospheres have occasionally been used to improve drug delivery during therapy [3,4]. Very recently, alginic acid based nanoparticles have also been used as effective drug delivery systems for various agents such as antitubercular [5,6], and antifungal drugs [7]. Alginate based nanoparticles usually have a high molecular weight in nature. These high molecular weight alginic acid based nanoparticles are highly limited for use in drug delivery due to their low water solubility [8,9]. The current trend in drug delivery systems has shifted towards the development of low molecular weight nanoparticle delivery systems, because these systems have higher solubility in water [10,11]. In addition, oxidized alginates contain more reactive groups and demonstrate faster degradation rates when used as support systems for controlled drug Dipankar Ghosh Département de Microbiologie et Immunologie, Université de Montréal, Quebec H3C 3J7, Canada Dipankar Ghosh, Arindam Pramanik, Narattam Sikdar, Panchanan Pramanik * Nanomaterials Laboratory, Department of Chemistry, Indian Institute of Technology, Kharagpur 721-302, India Tel: +91-03222-83322, Fax: +91-03222-255303 E-mail: dg.nanobio@gmail.com RESEARCH PAPER