Nanoparticle encapsulation of mitaplatin and the effect thereof on in vivo properties.
Nanoparticle encapsulation of mitaplatin and the effect thereof on in vivo properties.
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DOI：
10.1021/nn401905g
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发表时间：
2013-07-23
期刊：
影响因子：
17.1
通讯作者：
Lippard, Stephen J.
中科院分区：
文献类型：
--
作者：
Johnstone, Timothy C.;Kulak, Nora;Pridgen, Eric M.;Farokhzad, Omid C.;Langer, Robert;Lippard, Stephen J.
纳米颗粒（NP）疗法有可能显着改变其携带的药物活性剂的体内生物学特性。在这里，我们描述了一种称为 M-NP 的聚合物 NP 的开发，该聚合物 NP 包含聚（d,l-乳酸-共-乙醇酸）-嵌段聚（乙二醇）（PLGA-PEG），用聚乙烯醇（PVA）稳定，并负载有水溶性铂（IV）[Pt（IV）]前药米塔铂。米他铂，c,c,t-[PtCl2(NH3)2(OOCCHCl2)2] 是一种化合物，旨在释放顺铂（一种临床广泛使用的抗癌药物）和化学还原后的孤儿药二氯乙酸盐。报道了双乳化 M-NP 的优化制备及其物理表征，并评估了封装对铂剂性能的体内影响。封装增加了 Pt 在大鼠血流中的循环时间。小鼠体内 Pt 的生物分布也受到纳米颗粒封装的影响，导致肾脏中的积累减少。最后，通过三阴性乳腺癌小鼠异种移植模型中的肿瘤生长抑制来测量游离米塔铂和 M-NP 的疗效，表明纳米颗粒治疗随时间的推移控制释放米塔铂可产生与游离米塔铂相当的长期疗效，这可能会限制毒副作用。
Nanoparticle (NP) therapeutics have the potential to significantly alter the in vivo biological properties of the pharmaceutically active agents that they carry. Here we describe the development of a polymeric NP, termed M-NP, comprising poly(d,l-lactic-co-glycolic acid)-block-poly(ethylene glycol) (PLGA-PEG), stabilized with poly(vinyl alcohol) (PVA), and loaded with a water soluble platinum(IV) [Pt(IV)] prodrug, mitaplatin. Mitaplatin, c,c,t-[PtCl2(NH3)2(OOCCHCl2)2], is a compound designed to release cisplatin, an anticancer drug in widespread clinical use, and the orphan drug dichloroacetate following chemical reduction. An optimized preparation of M-NP by double emulsion and its physical characterization are reported and the influence of encapsulation on the properties of the platinum agent is evaluated in vivo. Encapsulation increases the circulation time of Pt in the bloodstream of rats. The biodistribution of Pt in mice is also affected by nanoparticle encapsulation, resulting in reduced accumulation in the kidneys. Finally, the efficacy of both free mitaplatin and M-NP, measured by tumor growth inhibition in a mouse xenograft model of triple-negative breast cancer, reveal that controlled release of mitaplatin over time from the nanoparticle treatment produces long-term efficacy comparable to that of free mitaplatin, which might limit toxic side effects.
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影响因子：
3
作者：
Hall, MD;Dillon, CT;Hambley, TW
通讯作者：
Hambley, TW
影响因子：
3
作者：
Gramatica, Paola;Papa, Ester;Osella, Domenico
通讯作者：
Osella, Domenico
影响因子：
56.9
作者：
HADEISHI, T;MCLAUGHL.RD
通讯作者：
MCLAUGHL.RD
DOI：
10.1073/pnas.0601755103
发表时间：
2006-04-18
影响因子：
11.1
作者：
Farokhzad, OC;Cheng, JJ;Langer, R
通讯作者：
Langer, R
DOI：
10.1073/pnas.1011379108
发表时间：
2011-02-01
影响因子：
11.1
作者：
Dhar, Shanta;Kolishetti, Nagesh;Farokhzad, Omid C.
通讯作者：
Farokhzad, Omid C.