ABSTRACT
Shoshy Mizrahy, MSc,a,b and Dan Peer, PhDa,baLaboratory of Nanomedicine, Department of Cell Research and Immunology, George S. Wise Faculty of Life Science, Tel Aviv University, Tel Aviv, Israel bCenter for Nanoscience and Nanotechnology Tel Aviv University, Tel Aviv, Israel Keywords: polysaccharides, glycosaminoglycans, hyaluronan, nanoparticles, liposomes
conceptual design toward pre-clinical and clinical applications. Over the past two decades, nanoparticle-based therapeutics have been introduced for the treatment of cancer, diabetes, allergy, inflammation, and infections [1, 2]. The growing interest in nanoparticles derives from the outstanding advantages they offer, which include protection of the drug from premature degradation, lower therapeutic toxicity, ability to deliver poorly-water-soluble drugs, controlled drug release mechanisms, and improved intracellular penetration [2].The size and surface characteristics of a nanoparticle are crucial for the control of its biodistribution in vivo. The small size, which enables nanoparticles to pass through the smallest capillaries also promotes passive tumor targeting due to the enhanced permeability and retention (EPR) effect of the tumor vasculature. The passive targeting is achieved by extravasation of nanoparticles through increased permeability of the tumor vasculature and ineffective lymphatic drainage [2]. In addition, it has been shown that a combination of nanometric size and hydrophilic surface delays particle uptake by the mononuclear phagocyte system (MPS) and therefore promotes long circulation [3]. As the requirements from the nanoparticle are becoming clear, so are the requirements from the materials used for their preparation. These materials should be biocompatible and preferably biodegradable, well characterized, and easily functionalized [2]. Polysaccharides successfully fulfill all of these requirements and are therefore widely used for the preparation of nanoparticles for drug delivery. 13.2 PolysaccharidesPolysaccharides are polymers of monosaccharides joined by glycosidic bonds. These highly abundant molecules are from various origins, including algal origin (e.g., alginate and carrageenan), plant origin (e.g., cellulose, pectin and guar gum), microbial origin (e.g., dextran and xanthan gum), and animal origin (e.g., chitosan, hyaluronan, chondroitin and heparin) [4]. Naturally occurring polysaccharides are diverse in their physiochemical properties; there are multiple chemical structures (Fig. 13.1), the chemical composition greatly varies and so do the molecular
weight (Mw) and ionic nature. This versatility also contributes to a wide range of biological activities. From a pharmaceutical standpoint, polysaccharides possess many favorable characteristics such as lack of toxicity, good biocompatibility stability, low cost, hydrophilic nature, and availability of reactive sites for chemical modification. In addition, many polysaccharides possess bioadhesive properties, especially for mucosal surfaces, which have been used for both targeting and prolonging drug residence time. All of these qualities have led to the growing use of polysaccharides in drug delivery systems.The properties of common polysaccharides used for the preparation of drug delivery systems are detailed below.
