Combinatorial co-encapsulation of hydrophobic molecules in poly(lactide-co-glycolide) microparticles.
Combinatorial co-encapsulation of hydrophobic molecules in poly(lactide-co-glycolide) microparticles.
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DOI：
10.1016/j.biomaterials.2013.01.032
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发表时间：
2013-04
期刊：
影响因子：
14
通讯作者：
Keselowsky, Benjamin G.
中科院分区：
文献类型：
--
作者：
Acharya, Abhinav P.;Lewis, Jamal S.;Keselowsky, Benjamin G.
人们对开发基于聚（丙交酯-共-乙交酯）（PLGA）的颗粒用于包封的生物分子的靶向递送和控制释放有很大兴趣。PLGA颗粒可用于递送蛋白质、小分子药物和核苷酸。此外，已经表明，PLGA颗粒中多种因子的共包封产生协同响应，并且可以同时提供治疗诊断益处。然而，可以通过颗粒中不同组分的组合产生的可能的独特颗粒制剂的数量随着每种新组分而急剧增加，并且目前没有方法产生如此巨大的独特PLGA颗粒库。为了解决这一差距，我们开发了一种高通量方法来生产数百个小批量的颗粒。通过改进的水包油乳液技术在多孔板威尔斯孔中产生颗粒。为了证明该技术的多功能性，制造了六种不同负载浓度的三种荧光染料的组合制剂，产生216种独特的PLGA颗粒制剂。我们展示了系统的和良好控制的组合加载到颗粒中的疏水分子。这种PPP方法增强了在标准聚苯乙烯多孔板中在不到24小时内产生数百种不同的具有多种共包封物的组合颗粒制剂，从而提供了快速、低成本、高通量的生产。我们设想，这种封装药物和成像模式组合的颗粒PPP文库随后可以以高通量方式在小细胞群上进行测试，并提供个性化药物。
There is a great interest for developing poly(lactide-co-glycolide) (PLGA) based particles for targeted delivery and controlled release of encapsulated biological molecules. The PLGA particles can be used to deliver proteins, small molecule drugs and nucleotides. Furthermore, it has been shown that the co-encapsulation of multiple factors in PLGA particles generates synergistic responses, and can simultaneously provide theranostic benefits. However, the number of possible unique particle formulations that may be generated by the combination of different components in a particle increases dramatically with each new component, and currently, there is no method to generate such a vast library of unique PLGA particles. In order to address this gap, we have developed a high-throughput methodology to produce hundreds of small batches of particles. The particles are generated in the multi-well plate wells by a modified oil-in-water emulsion technique. In order to demonstrate the versatility of this technique, combinatorial formulations of six different loading concentrations of three fluorescent dyes were fabricated giving rise to 216 unique PLGA particle formulations. We demonstrate systematic and well-controlled combinatorial loading of hydrophobic molecules into the particles. This PPP methodology potentiates the generation of hundreds of different combinatorial particle formulations with multiple co-encapsulates in less than 24 h in standard polystyrene multi-well plates, thus providing rapid, low cost, high-throughput production. We envision that such a PPP library of particles encapsulating combinations of drugs and imaging modalities can subsequently be tested on small populations of cells in a high-throughput fashion, and provide personalized medicine.
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DOI：
10.1016/j.jconrel.2010.05.032
发表时间：
2010-09-15
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Norton LW;Park J;Babensee JE
通讯作者：
Babensee JE
影响因子：
9.7
作者：
Acharya, Abhinav P.;Dolgova, Natalia V.;Keselowsky, Benjamin G.
通讯作者：
Keselowsky, Benjamin G.
影响因子：
14
作者：
Acharya, Abhinav P.;Clare-Salzler, Michael J.;Keselowsky, Benjamin G.
通讯作者：
Keselowsky, Benjamin G.
影响因子：
10.8
作者：
Diwan, M;Tafaghodi, M;Samuel, J
通讯作者：
Samuel, J
影响因子：
5.1
作者：
Lü JM;Wang X;Marin-Muller C;Wang H;Lin PH;Yao Q;Chen C
通讯作者：
Chen C