Formulation of functionalized PLGA-PEG nanoparticles for in vivo targeted drug delivery
Formulation of functionalized PLGA-PEG nanoparticles for in vivo targeted drug delivery
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DOI：
10.1016/j.biomaterials.2006.09.047
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发表时间：
2007-02-01
期刊：
影响因子：
14
通讯作者：
Farokhzad, Omid C.
中科院分区：
文献类型：
--
作者：
Cheng, Jianjun;Teply, Benjamin A.;Farokhzad, Omid C.
纳米粒子（NP）的大小已被证明会以器官特异性的方式显著影响靶向和非靶向纳米粒子的生物分布。在此，我们利用羧基封端的聚（D,L - 丙交酯 - 共 - 乙交酯） - 嵌段 - 聚（乙二醇）（PLGA - b - PEG - COOH）聚合物开发了纳米粒子，并研究了改变以下制剂参数对纳米粒子大小的影响：（1）聚合物浓度，（2）载药量，（3）溶剂与水的互溶性，以及（4）水与溶剂的比例。我们发现，对于直径在70到250纳米之间的纳米粒子，其平均体积大小与聚合物浓度呈线性相关（对于所研究的溶剂配制的纳米粒子，线性系数 = 0.99）。具有理想大小、载药量和多分散性的纳米粒子与结合前列腺特异性膜抗原（PSMA）的A10 RNA适体（Apt）偶联，并在前列腺癌的LNCaP（PSMA +）异种移植小鼠模型中评估了纳米粒子和纳米粒子 - 适体的生物分布。与不含A10 PSMA适体的等效纳米粒子相比，用A10 PSMA适体对纳米粒子进行表面功能化显著增强了纳米粒子向肿瘤的递送（在24小时时增加了3.77倍；每克组织中纳米粒子 - 适体为注射剂量的0.83%±0.21%，而纳米粒子为0.22%±0.07%；平均值±标准差，n = 4，p = 0.002）。控制纳米粒子大小以及靶向递送的能力可能会导致良好的生物分布以及临床相关靶向治疗的发展。（c）2006 Elsevier Ltd.保留所有权利。
Nanoparticle (NP) size has been shown to significantly affect the biodistribution of targeted and non-targeted NPs in an organ specific manner. Herein we have developed NPs from carboxy-terminated poly(D,L-lactide-co-glycolide)-block-poly(ethylene glycol) (PLGA-b-PEG-COOH) polymer and studied the effects of altering the following formulation parameters on the size of NPs: (1) polymer concentration, (2) drug loading, (3) water miscibility of solvent, and (4) the ratio of water to solvent. We found that NP mean volumetric size correlates linearly with polymer concentration for NPs between 70 and 250 nm in diameter (linear coefficient = 0.99 for NPs formulated with solvents studied). NPs with desirable size, drug loading, and polydispersity were conjugated to the A10 RNA aptamer (Apt) that binds to the prostate specific membrane antigen (PSMA), and NP and NP-Apt biodistribution was evaluated in a LNCaP (PSMA+) xenograft mouse model of prostate cancer. The surface functionalization of NPs with the A10 PSMA Apt significantly enhanced delivery of NPs to tumors vs. equivalent NPs lacking the A10 PSMA Apt (a 3.77-fold increase at 24 h; NP-Apt 0.83% +/- 0.21% vs. NP 0.22% +/- 0.07% of injected dose per grain of tissue; mean +/- SD, n = 4, p = 0.002). The ability to control NP size together with targeted delivery may result in favorable biodistribution and development of clinically relevant targeted therapies. (c) 2006 Elsevier Ltd. All rights reserved.