Chitosan nanoparticles (CS NPs) exhibit good physicochemical properties as drug delivery systems. The aim of this study is to determine the modulation of preparative parameters on the physical characteristics and colloidal stability of CS NPs. CS NPs were fabricated by ionic interaction with dextran sulphate (DS) prior to determination of their storage stability. The smallest CS NPs of ？nm with a surface charge of ？mV were produced when CS and DS were mixed at pH 4 and with a DS？:？CS mass ratio of 0.5？:？1. An entrapment efficiency of 98% was achieved when BSA/siRNA was loaded into the nanoparticles. The results also showed that particle size and surface charge of CS NPs were slightly changed up to 2 weeks when stored at 4°C. Greater particle size and surface charge were obtained with increasing the concentration of DS. In conclusion, NPs were sufficiently stable when kept at 4°C and able to carry and protect protein. 1. Introduction Endogenous peptides, protein, and oligonucleotides are among the main drugs which attract much attention because of their great potentials in treating chronic diseases [1]. However, the extreme in vivo environment of human body has always limited the therapeutic applications of these substances [2, 3]. Polymeric nanoparticles have attracted much attention as delivery systems due to their ability in overcoming the physiological barriers and protecting and targeting the loaded substances to specific cells [4, 5]. Naturally occurring polymers such as chitosan (CS) have been studied to form nanoparticles [6, 7]. CS is a biodegradable polysaccharide, and it is derived from deacetylation of chitin [8]. Apart from its biocompatibility, the low toxicity, hemostatic, and bacteriostatic properties also contribute to its various applications in pharmaceutical field [9–11]. Several anions have been investigated to crosslink CS like sodium sulphate [12] and dextran sulphate (DS) [13]. DS is able to modify protein and siRNA entrapment efficiency (EE) without the use of hardening agents and control the rate of drug release due to its high charge density [14]. Besides DS is a cheap material [15], it produces mechanically more stable nanoparticles compared to the pentasodium tripolyphosphate (TPP) [16, 17]. Several studies had reported the unique features of chitosan nanoparticles (CS NPs) using DS. However, the modulation of preparative parameters on their physical characteristics is still not fully investigated, for example, the influence of DS steric hindrance on the electrostatic attraction between CS and BSA [18]. Furthermore, the
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