Which polymer is more suitable for etoposide: A comparison between two kinds of drug loaded polymeric micelles in vitro and in vivo?
In this paper, we systemly compared the two kinds of VP16 (etoposide) loaded polymers micelles, monomethyl poly (ethylene glycol)-poly (lactic acid) (MPEG-PDLLA) and monomethyl poly (ethylene glycol)-poly (ϵ-caprolactone) (MPEG-PCL) in vitro and in vivo. Molecular modeling study was used as a novel means to compare the two formulations. In vitro, the micelle samples were fully characterized by TEM, XRD, drug loading (DL), Encapsulation efficiency (EE), stability and MTT. The stability study revealed that MPEG-PDLLA-VP16 had the significant advantage of 100% drug retention within 48 h compared to MPEG-PCL-VP16 with 40%, conform to the computer simulation model results. Cellular uptake figured that MPEG-PDLLA-VP16 had a 7 times larger uptake rate in the H460 cell line. In vivo, pharmacodynamics results showed MPEG-PDLLA-VP16 perform no significant difference with VP16 clinical formulations (10, 20mg/kg). However, MPEG-PCL-VP16 had no difference between different dosages on anticancer activities. Plasma pharmacokinetics results showed that the two micelle formulations prolong the half-life of VP16 twice than that of VP16 clinical formulations. In conclusion, micelle were better choice for cancer treatment on reducing drug toxic. In this study, the results also indicated that MPEG-PDLLA was more suitable for VP16 than MPEG-PCL as a more promising formulation for clinical cancer treatment.
State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
Lijuan
L
Chen
State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
Liwei
L
Tan
School of Medicine, Tsinghua University, Beijing 100084, PR China.
Xiaoning
X
Zhang
School of Medicine, Tsinghua University, Beijing 100084, PR China.
Jun
J
Li
State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China. Electronic address: anderson-qian@163.com.
Zhiyong
Z
Qian
State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China. Electronic address: tmkxiang@163.com.
Mingli
M
Xiang
State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
Yuquan
Y
Wei
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D041702:BALB 3T3 Cells; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival; D004337:Drug Carriers / Q000737:chemistry; D005047:Etoposide / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D005434:Flow Cytometry; D006207:Half-Life; D006801:Humans; D007773:Lactates / Q000737:chemistry*; D051379:Mice; D008823:Micelles; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar
D000970:Antineoplastic Agents; D004337:Drug Carriers; D007773:Lactates; D008823:Micelles; D011091:Polyesters; C439611:methoxy poly(ethylene glycol-co-epsilon-caprolactone); C088513:poly(lactic acid-ethylene glycol); D011092:Polyethylene Glycols; D005047:Etoposide
MPEG-PCL; MPEG-PDLLA; Micelle; VP16