Novel Hydroxyapatite-Polysaccharide Composite Microparticles for Immunotherapy
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Novel Hydroxyapatite-Polysaccharide Composite Microparticles for Immunotherapy
Mitsuhiro Yoshida, Tomohiko Yoshioka, Toshiyuki Ikoma, and Junzo Tanaka Department of Metallurgy and Ceramics Science, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8550 Japan
ABSTRACT Hydroxyapatite-chondroitin sulfate (HAp/ChS) composites were synthesized with calcium hydroxide suspension and phosphoric acid solution containing ChS through a precipitation method, and the microparticles were then fabricated by a spray dry method with the suspension of the composites. Bovine serum albumin (BSA) with negative charge or lysozyme (LYZ) with positive charge at pH7.0 was adsorbed onto the HAp/ChS microparticles. However, the HAp/ChS microparticles adsorbed LYZ more than the HAp microparticles compared with BSA due to the electrostatic interaction from negatively-charged sulfate or carboxyl group of ChS in the composites. The release property of BSA from the HAp/ChS microparticles was evaluated in Dulbecco’s phosphate buffered saline (pH7.2). The HAp/ChS microparticles released quickly 100% of the adsorbed BSA, while HAp microparticles released 45% of BSA. These results indicated that incorporation of ChS in the microparticles controls the adsorption and release properties of protein due to the electrostatic interaction. The HAp/ChS microparticles therefore are a candidate of a carrier for drugs like vaccines. INTRODUCTION Immunotherapy is a non-invasive treatment method which can control the immune response, and is usually conducted via vaccination. Antigen presenting cells (APC) such as dendritic cells and macrophages ingest vaccines (antigens) injected at lymph nodes, and present antigens in association with human leukocyte antigen (HLA) class I or II molecules on the surface of them. Then, the antigens presented on APC stimulate T lymphocytes to make antigenspecific cytotoxic T lymphocytes (CTL) and helper T cells. Finally, the antigen-specific CTL activated by helper T cells eradicate cancer cells with the same antigen on their surfaces [1-3]. However it was difficult to induce fully activated antigen-specific CTL [4]. The solutions to overcome this problem are to use drug carriers and adjuvants which can carry injected vaccines into APC effectively and can activate immune systems, respectively. Thus, novel vaccine carriers with controlled-release to induce adjuvant action have been investigated. Hydroxyapatite (HAp; Ca10(PO4)6(OH)2) is a main component of bone and is used for a bone-substituted material [5]. HAp is known as a biocompatible carrier with high affinity for proteins [6]. Chondroitin sulfate (ChS) is one of glycosamioglycans found in cartilage as a main component, and has highly negative charge derived from its sulfate group and carboxylate group [7]. In this study, we fabricated hydroxyapatite-chondroitin sulfate (HAp/ChS) composite microparticles as a carrier for model vaccines, that is bovine serum albumin (BSA, pI=4.6) and lysozyme (LYZ, pI=11.0), and examined the adsorption and release properties
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