title: A novel paclitaxel-loaded poly(epsilon-caprolactone)/Poloxamer 188 blend nanoparticle overcoming multidrug resistance for cancer treatment.
abstract: Multidrug resistance (MDR) of tumor cells is a major obstacle to the success of cancer chemotherapy. Poloxamers have been used in cancer therapy to overcome MDR. The objective of this research is to test the feasibility of paclitaxel-loaded poly(epsilon-caprolactone)/Poloxamer 188 (PCL/Poloxamer 188) nanoparticles to overcome MDR in a paclitaxel-resistant human breast cancer cell line. Paclitaxel-loaded nanoparticles were prepared by a water-acetone solvent displacement method using commercial PCL and self-synthesized PCL/Poloxamer 188 compound, respectively. PCL/Poloxamer 188 nanoparticles were found to be of spherical shape and tended to have a rough and porous surface. The nanoparticles had an average size of around 220nm, with a narrow size distribution. The in vitro drug release profile of both nanoparticle formulations showed a clear biphasic release pattern. There was an increased level of uptake of PCL/Poloxamer 188 nanoparticles (PPNP) in the paclitaxel-resistant human breast cancer cell line MCF-7/TAX, in comparison with PCL nanoparticles. The cytotoxicity of PCL nanoparticles was higher than commercial Taxol in the MCF-7/TAX cell culture, but the differences were not significant. However, the PCL/Poloxamer 188 nanoparticles achieved a significantly higher level of cytotoxicity than both of PCL nanoparticle formulation and Taxol(R), indicating that paclitaxel-loaded PCL/Poloxamer 188 nanoparticles could overcome MDR in human breast cancer cells and therefore could have considerable therapeutic potential for breast cancer.
authors.affiliation: Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, People's Republic of China.
authors.forename: Yangqing
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lina
authors.initials: L
authors.lastname: Tang
authors.forename: Leilei
authors.initials: L
authors.lastname: Sun
authors.forename: Junbo
authors.initials: J
authors.lastname: Bao
authors.forename: Cunxian
authors.initials: C
authors.lastname: Song
authors.forename: Laiqiang
authors.initials: L
authors.lastname: Huang
authors.forename: Kexin
authors.initials: K
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Tian
authors.forename: Ge
authors.initials: G
authors.lastname: Tian
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.forename: Hongfan
authors.initials: H
authors.lastname: Sun
authors.forename: Lin
authors.initials: L
authors.lastname: Mei
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D018432:Drug Resistance, Multiple; D006801:Humans; D008422:Materials Testing; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry*; D020442:Poloxamer / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D011091:Polyesters; D020442:Poloxamer; C016240:polycaprolactone; D017239:Paclitaxel