School of Materials Science & Engineering, College of Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore; Department of Physiology and Immunology Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456, Singapore.
San Francisco Graduate Program in Bioengineering, University of California, Berkeley, Berkeley, California 94720.
J Pharm Sci. 2019 Jul;108(7):2430-2437. doi: 10.1016/j.xphs.2019.02.024. Epub 2019 Mar 6.
Laboratory investigations of polyester biomaterials overly rely on additives and solvent-casting manufacturing techniques that do not allow translation into industrial processing owing to the volatile organic compounds present. These impediments of bench to bedside translation are addressed with a "green chemistry" twin screw extrusion approach, where the extrusion parameters control the release profile. Advantages include elimination of volatile organic compounds, removal of plastic plasticizers/additives, and a low temperature production that is applicable to both academia and industry. Poly (d, l-lactide-co-glycolide) (PLGA), a labile polyester drug depot is loaded with fluorescein diacetate (FDAc), a pH/heat sensitive drug that degrades to fluorescein. Processing of FDAc suggests no degradation at elevated temperatures or high shears, indicating hydrophobic small molecules can be homogeneously dispersed with no detrimental effects. In vitro release of FDAc in physiological environments varies release profile through ratios of ester/acid-terminated PLGA without secondary additives. Postprocessing stability investigations of PLGA resin with size exclusion chromatography and differential scanning calorimetry validate no significant polymer degradation. Through judicious choice of parameters, release can be tuned from 15-250 microgram per sq. cm per day. Twin screw extrusion production of PLGA drug depots reveals a promising method of tailor-made drug delivering thin films for various pharmaceutical applications.
实验室对聚酯生物材料的研究过度依赖添加剂和溶剂浇铸制造技术，由于存在挥发性有机化合物，这些技术无法转化为工业加工。通过“绿色化学”双螺杆挤出方法解决了从实验室到临床的转化障碍，其中挤出参数控制释放曲线。优点包括消除挥发性有机化合物、去除塑料增塑剂/添加剂，以及适用于学术界和工业界的低温生产。聚（D，L-丙交酯-共-乙交酯）（PLGA）是一种不稳定的聚酯药物库，负载有荧光素二乙酸酯（FDAc），这是一种对 pH 值/热敏感的药物，会降解为荧光素。FDAc 的加工表明在高温或高剪切下没有降解，表明疏水分子可以均匀分散，没有不利影响。在生理环境中，FDAc 的体外释放通过无二次添加剂的酯/酸封端 PLGA 的比例改变释放曲线。使用尺寸排阻色谱法和差示扫描量热法对 PLGA 树脂进行的后处理稳定性研究验证了聚合物没有发生明显降解。通过明智地选择参数，可以将释放速率调整为每天每平方厘米 15-250 微克。PLGA 药物库的双螺杆挤出生产为各种药物应用提供了一种有前途的定制药物输送薄膜的方法。
