Long-Term Antibody Release Polycaprolactone Capsule and the Release Kinetics in Natural and Accelerated Degradation.
Long-Term Antibody Release Polycaprolactone Capsule and the Release Kinetics in Natural and Accelerated Degradation.
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长期抗体释放聚己内酯胶囊以及自然和加速降解中的释放动力学。
DOI：
10.1021/acsbiomaterials.2c00808
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发表时间：
2022
影响因子：
5.8
通讯作者：
Park,YoonjeeC
中科院分区：
文献类型：
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作者：
Waterkotte,Thomas;He,Xingyu;Wanasathop,Apipa;Li,SKevin;Park,YoonjeeC
尽管使用单克隆抗体（mAb）的治疗在过去20年中已经取得了稳定的成功，但是mAb的递送方式尚未优化，特别是对于长期递送。频繁注射或输注已成为当前的护理标准。在这项研究中，我们已经开发了一种长期的抗体生物可降解植入物使用多孔聚己内酯（PCL）胶囊。迄今为止，它缓慢释放贝伐单抗（Bev）8个月。Bev的释放动力学符合药物释放模型，其扩散系数和分配系数的实验数据通过聚合物胶囊。由于筛选长期（>6个月）的药物释放曲线很耗时，因此在验证了自然和加速降解条件下PCL胶囊的特征后，使用了加速降解方法。确定了自然降解和加速降解之间的时间段相关性。总体而言，该研究表明，mAb可以从多孔PCL胶囊中释放，而不会在长时间内（约6个月）受到聚合物降解的影响，并且可以通过14天内的加速降解来确定长期释放动力学。
Although therapy using monoclonal antibodies (mAbs) has been steadily successful over the last 20 years, the means of delivery of mAbs has not been optimized, especially for long-term delivery. Frequent injections or infusions have been the current standard of care. In this study, we have developed a long-term antibody biodegradable implant using a porous polycaprolactone (PCL) capsule. It released bevacizumab (Bev) slowly for 8 months to date. The Bev release kinetics fit a drug release model with experimental data of the diffusion coefficient and partition coefficient through the polymer capsule. Since screening drug release profiles for the long term (>6 months) is time consuming, an accelerated degradation method was used after validating the characteristics of the PCL capsule in natural and accelerated degradation conditions. The correlation of the time period between natural and accelerated degradation was determined. Overall, the study suggests that mAbs can be released from a porous PCL capsule without an effect of the polymer degradation over a long period (∼6 months) and the long-term release kinetics can be determined by the accelerated degradation within 14 days.