Waterkotte Thomas, He Xingyu, Wanasathop Apipa, Li S Kevin, Park Yoonjee C
Department of Chemical & Environmental Engineering, University of Cincinnati, 2901 Woodside Dr., Cincinnati, Ohio 45221, United States.
College of Pharmacy, University of Cincinnati, 3255 Eden Ave, Cincinnati, Ohio 45229, United States.
ACS Biomater Sci Eng. 2022 Oct 10;8(10):4428-4438. doi: 10.1021/acsbiomaterials.2c00808. Epub 2022 Sep 28.
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.
尽管在过去20年中，使用单克隆抗体（mAb）的治疗一直稳步取得成功，但mAb的递送方式尚未得到优化，尤其是对于长期递送而言。频繁注射或输注一直是当前的护理标准。在本研究中，我们使用多孔聚己内酯（PCL）胶囊开发了一种长期抗体可生物降解植入物。迄今为止，它已缓慢释放贝伐单抗（Bev）达8个月。Bev的释放动力学符合通过聚合物胶囊的扩散系数和分配系数的实验数据的药物释放模型。由于长期（>6个月）筛选药物释放曲线耗时，在验证PCL胶囊在自然和加速降解条件下的特性后，采用了加速降解方法。确定了自然降解和加速降解之间时间段的相关性。总体而言，该研究表明，mAb可以从多孔PCL胶囊中释放，在很长一段时间（约6个月）内不受聚合物降解的影响，并且长期释放动力学可以在14天内通过加速降解来确定。
