title: Self-assembled nanoparticles based on chondroitin sulfate-deoxycholic acid conjugates for docetaxel delivery: Effect of degree of substitution of deoxycholic acid.
abstract: Hydrophobically-modified polymers based on chondroitin sulfate with different degree of substitution (DS) of deoxycholic acid (DOCA) were developed for docetaxel delivery. Chondroitin sulfate-deoxycholic acid (CSAD) bioconjugates were synthesized via the linker of adipic dihydrazide by amide bond. They were characterized with spherical shape, mean diameter of around 165.2nm and negative zeta potential (-14.87 to -20.53mV). An increase of DOCA DS reduced size of nanoparticles, while increasing drug loading efficiency. Drug release in vitro showed a triphasic sustained pattern and higher accumulative drug release percentage was observed with increased DS of DOCA on polymer. Self-assemblies with higher DS also had enhanced internalization of nanoparticles and stronger cytotoxicity at the cellular level. The self-assemble nanoparticles demonstrate to be excellent targeting drug delivery systems and the desired therapeutics can be achieved via the alteration of DS.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan 250012, China.
authors.forename: Mengrui
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan 250012, China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Du
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan 250012, China. Electronic address: professorgxzhai@126.com.
authors.forename: Guangxi
authors.initials: G
authors.lastname: Zhai
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation; D002809:Chondroitin Sulfates / Q000737:chemistry*; D003840:Deoxycholic Acid / Q000737:chemistry*; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005260:Female; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D053758:Nanoparticles / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D043823:Taxoids / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D011108:Polymers; D043823:Taxoids; D003840:Deoxycholic Acid; D000077143:Docetaxel; D002809:Chondroitin Sulfates
keywords: CD44 receptor; Chondroitin sulfate; Degree of substitution; Docetaxel; Nanoparticles; Self-assembly