Nanyang Technological University, Materials and Science Engineering, Division of Materials Technology, Singapore 639798, Singapore.
Acta Biomater. 2012 Jul;8(6):2263-70. doi: 10.1016/j.actbio.2012.01.014. Epub 2012 Jan 18.
Pure polymer films cannot meet the diverse range of controlled release and material properties demanded for the fabrication of medical implants or other devices. Additives are added to modulate and optimize thin films for the desired qualities. To characterize the property trends that depend on additive concentration, an assay was designed which involved casting a single polyester poly(lactic-co-glycolic acid) (PLGA) film that blends a linear gradient of any PLGA-soluble additive desired. Four gradient PLGA films were produced by blending polyethylene glycol or the more hydrophobic polypropylene glycol. The films were made using a custom glass gradient maker in conjunction with a 180 cm film applicator. These films were characterized in terms of thickness, percent additive, total polymer (PLGA+additive), and controlled drug release using drug-like fluorescent molecules such as coumarin 6 (COU) or fluorescein diacetate (FDAc). Material properties of elongation and modulus were also accessed. Linear gradients of additives were readily generated, with phase separation being the limiting factor. Additive concentration had a Pearson's correlation factor (R) of >0.93 with respect to the per cent total release after 30 days for all gradients characterized. Release of COU had a near zero-order release over the same time period, suggesting that coumarin analogs may be suitable for use in PLGA/polyethylene glycol or PLGA/polypropylene glycol matrices, with each having unique material properties while allowing tuneable drug release. The gradient casting method described has considerable potential in offering higher throughput for optimizing film or coating material properties for medical implants or other devices.
纯聚合物薄膜无法满足医学植入物或其他设备制造所需的各种控制释放和材料性能要求。需要添加添加剂来调节和优化薄膜以获得所需的质量。为了表征依赖于添加剂浓度的性能趋势,设计了一种分析方法,该方法涉及铸造单层聚酯聚(乳酸-共-乙醇酸)(PLGA)薄膜,该薄膜混合了所需的任何 PLGA 可溶性添加剂的线性梯度。通过混合聚乙烯醇或疏水性更强的聚丙二醇来制备四种梯度 PLGA 薄膜。使用定制的玻璃梯度制造商和 180cm 的薄膜涂布器来制备这些薄膜。根据厚度、添加剂百分比、总聚合物(PLGA+添加剂)以及使用类似药物的荧光分子(如香豆素 6(COU)或荧光素二乙酸酯(FDAc))进行控制药物释放来对这些薄膜进行了表征。还评估了伸长率和模量等材料性能。很容易产生添加剂的线性梯度,相分离是限制因素。对于所有特征化的梯度,添加剂浓度与 30 天后的总释放百分比之间的 Pearson 相关系数(R)>0.93。在相同时间段内,COU 的释放接近零级释放,这表明香豆素类似物可能适合用于 PLGA/聚乙二醇或 PLGA/聚丙二醇基质,每种基质都具有独特的材料性能,同时允许调节药物释放。所描述的梯度铸造方法在优化用于医学植入物或其他设备的薄膜或涂层材料性能方面具有很大的潜力,可以提高高通量。