title: Folate and CD44 receptors dual-targeting hydrophobized hyaluronic acid paclitaxel-loaded polymeric micelles for overcoming multidrug resistance and improving tumor distribution.
abstract: The drug efflux mediated by P-glycoprotein (P-gp) transporter is one of the important factors responsible for multidrug resistance (MDR), and then the efficient intracellular drug delivery is an important strategy to overcome MDR of tumor cells. We describe and compare CD44 receptor single-targeting and folate (FA), CD44 receptors dual-targeting hyaluronic acid-octadecyl (HA-C18 ) micellar formulations to overcome MDR of tumor cells and to improve tumor distribution. In comparison with Taxol solution, the cytotoxicity of paclitaxel (PTX) loaded in HA-C18 and FA-HA-C18 micelles against drug-resistant tumor cells was improved significantly because of the increased intracellular delivery by active receptor-mediated endocytosis. Compared with the single-targeting micelles, dual-targeting micelles possessed better MDR-overcoming performance. Pharmacokinetic study demonstrated HA-C18 and FA-HA-C18 PTX-loaded micelles possessed much longer circulation and moderately larger AUC than Taxol solution. Above all, the tumor distribution in MCF-7 tumor-bearing mice of PTX encapsulated in HA-C18 and FA-HA-C18 micelles were 2.8 and 4.0 times higher than that of Taxol solution. It was concluded that dual-targeting FA-HA-C18 micelles demonstrate excellent MDR-overcoming ability and improved tumor distribution, and provide a novel effective nanoplatform for anticancer drug delivery in cancer chemotherapy.
authors.affiliation: Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China; Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University, Yinchuan, 750004, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Liu
authors.forename: Jin
authors.initials: J
authors.lastname: Sun
authors.forename: He
authors.initials: H
authors.lastname: Lian
authors.forename: Wen
authors.initials: W
authors.lastname: Cao
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhonggui
authors.initials: Z
authors.lastname: He
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005492:Folic Acid / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000737:chemistry / Q000494:pharmacology*; D061986:MCF-7 Cells; D008297:Male; D051379:Mice; D008823:Micelles; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology*; D017208:Rats, Wistar
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D018960:Hyaluronan Receptors; D008823:Micelles; D006820:Hyaluronic Acid; D005492:Folic Acid; D017239:Paclitaxel
keywords: PTX; cancer chemotherapy; multidrug resistance; nanotechnology; polymeric drug delivery systems; targeted drug delivery; tumor targeting