A novel paclitaxel-loaded poly(epsilon-caprolactone)/Poloxamer 188 blend nanoparticle overcoming multidrug resistance for cancer treatment.
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.
Zhang
Yangqing
Y
Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, People's Republic of China.
Tang
Lina
L
Sun
Leilei
L
Bao
Junbo
J
Song
Cunxian
C
Huang
Laiqiang
L
Liu
Kexin
K
Tian
Yan
Y
Tian
Ge
G
Li
Zhen
Z
Sun
Hongfan
H
Mei
Lin
L
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*
D000970:Antineoplastic Agents; D004337:Drug Carriers; D011091:Polyesters; D020442:Poloxamer; C016240:polycaprolactone; D017239:Paclitaxel