Strategy for Synthesis of Statistically Sequence-Controlled Uniform PLGA and Effects of Sequence Distribution on Interaction and Drug Release Properties
Strategy for Synthesis of Statistically Sequence-Controlled Uniform PLGA and Effects of Sequence Distribution on Interaction and Drug Release Properties
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统计序列控制的均匀 PLGA 的合成策略以及序列分布对相互作用和药物释放特性的影响
DOI：
10.1021/acsmacrolett.1c00637
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发表时间：
2021
影响因子：
7.015
通讯作者：
Won, You-Yeon
中科院分区：
文献类型：
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作者：
Yoo, Jin;Viswanath, Dhushyanth;Won, You-Yeon
已经进行了广泛的研究，以阐明这些参数的影响，如分子量，多分散性，和组成上的控制释放性能的聚（d，l-乳酸-共-乙醇酸）（PLGA）。然而，处理单体序列分布的影响的研究已经稀疏，主要是因为在PLGA中精确控制单体序列的困难。在此，我们提出了一种半间歇共聚策略，通过控制共聚单体的添加速率，能够生产统计序列控制的“均匀PLGA”聚合物。使用该方法，制备了一系列具有相当的分子量和组成但不同序列分布（均匀与梯度）的PEG-PLGA样品。发现这些材料的性质（PEG结晶/熔融、吸湿性、水溶胶-凝胶转变、药物释放动力学）显著变化，表明仅在统计水平上的序列控制仍然显著影响PLGA的性质。最值得注意的是，与梯度PLGA相比，均匀PLGA表现出更持续的药物释放行为。
Extensive studies have been conducted to elucidate the effects of such parameters as molecular weight, polydispersity, and composition on the controlled release properties of poly(d,l-lactic-co-glycolic acid) (PLGA). However, studies dealing with the effect of monomer sequence distribution have been sparse mainly because of the difficulty of precisely controlling the monomer sequence in PLGA. Herein, we present a semibatch copolymerization strategy that enables the production of statistically sequence-controlled “uniform PLGA” polymers through control of the rate of comonomer addition. Using this method, a series of PEG–PLGA samples having a comparable molecular weight and composition but different sequence distributions (uniform vs gradient) were prepared. The properties of these materials (PEG crystallization/melting, hygroscopicity, aqueous sol–gel transition, drug release kinetics) were found to significantly vary, demonstrating that sequence control only at the statistical level still significantly influences the properties of PLGA. Most notably, uniform PLGA exhibited the more sustained drug release behavior compared to gradient PLGA.