329 Introduction Over the past few decades, focus has been given to drug targeting in pharmaceutical industries to prevent the usage of excessive drugs during medication to reduce the toxicity and side effects caused by undesired drug localization (Yuan et al., 2010). Currently, liposomes have drawn much attention in the pharmaceutical industry as a drug delivery vehicle. e ability of the liposome to encapsulate and protect active drugs enabled it to deliver drugs to the desired disease sites. Commercially available liposome and liposome-like pharmaceutical products, such as DOXIL, have been developed and successfully applied for the delivery of anticancer drug, such as doxorubicin, for the treatment of breast cancer (Torchilin, 2005). However, researches have revealed that conventional liposome hardly survive in the bloodstream because it can be easily detected and destroyed by the immune system. is disadvantage has limited the application of conventional liposome as a drug carrier (Immordino et al., 2006). Consequently, PEGylated liposomes with longer circulation times (He et al., 2010) have been developed to overcome this problem. PEG (polyethylene glycol) is a synthetic, nontoxic polymer that has been used to modify the surface of the liposome for the enhancement of liposome stability in the bloodstream (Chonn and Cullis, 1998; Taguchi et al., 2009). Again, studies have revealed that repeated injections of the PEGylated liposome can induce the accelerated blood clearance phenomenon and reduce the bioavailability of the PEGylated liposome (Laverman et al., 2001; Ishida et al., 2005). erefore, various polymers, especially polysaccharides, have been used to replace PEG (Mobed and Chang, 1998; Filipovicâ-Grcïicâ et al., 2001; ongborisute et al., 2006). Among polysaccharides, chitosan has been the most widely used coating material for liposomes because of its biocompatibility, biodegradability, nontoxicity, bioadhesivity (Adamo and Isabella, 2003; Aranaz et al., 2010), and mucoadhesive properties (Karn et al., 2011). Takeuchi et al. (1996, 2003) reported that chitosan-coated liposomes were able to prolong the pharmacokinetic effect of peptides (e.g., insulin) as a result of the mucoadhesion of the liposome to the intestinal tract. Chitosan can also increase the stability and prolong the blood-circulation time of the RESEARCH ARTICLE Characterization of fatty acid liposome coated with low-molecular-weight chitosan Hsiao Wei Tan and Misni Misran Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia Abstract Preparation of chitosan-coated fatty acid liposomes is often restricted by the solubility of chitosan under basic conditions. In this experiment, the preparation of chitosan-coated oleic acid (OA) liposomes using low molecular weight (LMW) chitosan (10 and 25 kDA) was demonstrated. These selected LMW chitosans are water soluble. The coating of the chitosan layer on OA liposomes was confirmed by its microscope images and physicochemical properties, such as zeta potential and the size of the liposomes. The “peeling off” effect on the surface of chitosan- coated OA liposomes was observed in the atomic force microscope images and showed the occurrence of the chitosan layer on the surface of OA liposomes. The size of the chitosan-coated liposomes was at least 20 nm smaller than the OA liposomes, and the increase of zeta potential with the increasing amount of LMW chitosan further confirmed the presence of the surface modification of OA liposomes. Keywords: Oleic acid vesicle, surface tension, atomic force microscope, drug delivery Address for Correspondence: Hsiao Wei Tan, Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia. Fax: +603–79674193. E-mail: weith83@gmail.com (Received 04 January 2012; revised 30 April 2012; accepted 02 June 2012) Journal of Liposome Research, 2012; 22(4): 329–335 © 2012 Informa Healthcare USA, Inc. ISSN 0898-2104 print/ISSN 1532-2394 online DOI: 10.3109/08982104.2012.700459