Which polymer is more suitable for etoposide: A comparison between two kinds of drug loaded polymeric micelles in vitro and in vivo?

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• 作者：Lijuan Chen^a ; Liwei Tan^a ; Xiaoning Zhang^b ; Jun Li^b ; Zhiyong Qian^a ; ^{anderson-qian@163.com" class="auth_mail" title="E-mail the corresponding author} ; Mingli Xiang^a ; ^{tmkxiang@163.com" class="auth_mail" title="E-mail the corresponding author} ; Yuquan Wei^a
• 关键词：Micelle ; MPEG-PDLLA ; MPEG-PCL ; VP16
• 刊名：International Journal of Pharmaceutics
• 出版年：2015
• 出版时间：10 November 2015
• 年：2015
• 卷：495
• 期：1
• 页码：265-275
• 全文大小：3205 K

文摘

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 (系-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, 20 mg/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.