Dimeric Drug Polymeric Nanoparticles with Exceptionally High Drug Loading and Quantitative Loading Efficiency
Dimeric Drug Polymeric Nanoparticles with Exceptionally High Drug Loading and Quantitative Loading Efficiency
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DOI：
10.1021/ja513034e
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发表时间：
2015-03-18
影响因子：
15
通讯作者：
Cheng, Jianjun
中科院分区：
文献类型：
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作者：
Cai, Kaimin;He, Xi;Cheng, Jianjun
在疏水聚合物或两亲共聚物中包封小分子药物已被广泛用于制备纳米聚合物。然而，在聚合物NPs中，许多药物的装载和装载效率往往很低。在本通讯中，我们报告了一种制备具有极高载药量（bbb50 %）和定量载药量效率的聚合物NPs的策略。具体来说，设计了一个带有触发反应结构域的二聚体药物偶联物，并将其用作NPs的核心构建单元。二聚体药物与甲氧基聚乙二醇嵌段聚乳酸（mPEG-PLA）共沉淀，形成具有二聚体药物核和聚合物壳的np。高载药NPs在生理条件下表现出良好的稳定性。PBS溶液中未见无触发的药物提前释放或前药释放，而外部触发导致药物以原形控释。
Encapsulation of small-molecule drugs in hydrophobic polymers or amphiphilic copolymers has been extensively used for preparing polymeric nanoparticles (NPs). The loadings and loading efficiencies of a wide range of drugs in polymeric NPs, however, tend to be very low. In this Communication, we report a strategy to prepare polymeric NPs with exceptionally high drug loading (>50%) and quantitative loading efficiency. Specifically, a dimeric drug conjugate bearing a trigger-responsive domain was designed and used as the core-constructing unit of the NPs. Upon co-precipitation of the dimeric drug and methoxypoly(ethylene glycol)-block-polylactide (mPEG-PLA), NPs with a dimeric drug core and a polymer shell were formed. The high-drug-loading NPs showed excellent stability in physiological conditions. No premature drug or prodrug release was observed in PBS solution without triggering, while external triggering led to controlled release of drug in its authentic form.