Preparation and evaluation of teniposide-loaded polymeric micelles for breast cancer therapy.
Self-assembled polymeric micelles have been widely applied in anticancer drug delivery systems. Teniposide is a broad spectrum and effective anticancer drug, but its poor water-solubility and adverse effects of commercial formulation (VM-26) restrict its clinical application. In this work, teniposide-loaded polymeric micelles were prepared based on monomethoxy-poly(ethylene glycol)-poly(ε-caprolactone-co-d,l- lactide) (MPEG-PCLA) copolymers through a thin-film hydration method to improve the hydrophilic and reduce the systemic toxicity. The prepared teniposide micelles were without any surfactants or additives and monodisperse with a mean particle size of 29.6±0.3nm. The drug loading and encapsulation efficiency were 18.53±0.41% and 92.63±2.05%, respectively. The encapsulation of teniposide in MPEG-PCLA micelles showed a slow and sustained release behavior of teniposide in vitro and improved the terminal half-life (t1/2), the area under the plasma concentration-time curve (AUC) and retention time of teniposide in vivo compared with VM-26. In addition, teniposide micelles also enhanced the cellular uptake by MCF-7 breast cancer cells in vitro and increased the distribution in tumors in vivo. Teniposide micelles showed an excellent safety with a maximum tolerated dose (MTD) of approximately 50mg teniposide/kg body weight, which was 2.5-fold higher than that of VM-26 (about 20mg teniposide/kg body weight). Furthermore, the intravenous application of teniposide micelles effectively suppressed the growth of subcutaneous MCF-7 tumor in vivo and exhibited a stronger anticancer effect than that of VM-26. These results suggested that we have successfully prepared teniposide-loaded MPEG-PCLA micelles with improved safety, hydrophilic and therapeutic efficiency, which are efficient for teniposide delivery. The prepared teniposide micelles may be promising in breast cancer therapy.
Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou 325000, PR China. Electronic address: chubingyang@126.com.
Bingyang
B
Chu
Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou 325027, PR China.
Shuai
S
Shi
Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou 325027, PR China.
Xingyi
X
Li
Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou 325000, PR China.
Lufeng
L
Hu
Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou 325000, PR China.
Lu
L
Shi
Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou 325000, PR China.
Haina
H
Zhang
Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou 325000, PR China.
Qiaoqiao
Q
Xu
Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou 325000, PR China.
Lei
L
Ye
Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou 325000, PR China.
Guanyang
G
Lin
Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou 325000, PR China.
Nansheng
N
Zhang
Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou 325000, PR China. Electronic address: wzxiuhuazhang@163.com.
Xiuhua
X
Zhang
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D019540:Area Under Curve; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D005260:Female; D006207:Half-Life; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D061986:MCF-7 Cells; D020714:Maximum Tolerated Dose; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008823:Micelles; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013713:Teniposide / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; C505727:poly(epsilon-caprolactone-co-lactide); D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol; D013713:Teniposide
Breast cancer therapy; MPEG-PCLA; Polymeric micelles; Teniposide