Chiba M, Hanes J, Langer R
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge 02139, USA.
Biomaterials. 1997 Jul;18(13):893-901. doi: 10.1016/s0142-9612(97)00027-6.
Polymer microspheres capable of the controlled release of macromolecules for periods ranging from days to over a month were developed. The microspheres were made using a new family of anhydride polymers: tyrosine-containing poly(anhydride-co-imides), specifically poly[trimellitylimido-L-tyrosine-co-sebacic acid-co-1,3-bis(carboxphenoxy)propane] anhydrides [poly(TMA-Tyr:SA:CPP)]. These polymers may be of particular interest for controlled delivery of vaccine antigens due to the incorporation of an immunological adjuvant, L-tyrosine, into their backbone. Microspheres were produced from a variety of polymer compositions using a double-emulsion solvent-evaporation technique, and tested for their ability to provide controlled release of a model protein, bovine serum albumin, in vitro. The microspheres are spherical with smooth surfaces and encapsulate greater than 70% of the protein. Protein release rates from polymers of identical composition could be varied from 0.3 to over 125 micrograms per mg spheres per month by changing the amount of protein encapsulated. This effect can be magnified by using polymers with various monomer ratios. A close correlation between protein release and polymer weight loss was observed, suggesting a release mechanism controlled mainly by polymer erosion. Bovine serum albumin release from poly(TMA-Tyr:SA:CPP) microspheres is also pH sensitive, being enhanced at high pH and depressed under acidic conditions.
已开发出能够在数天至一个多月的时间内控制释放大分子的聚合物微球。这些微球是使用一类新的酸酐聚合物制成的：含酪氨酸的聚（酸酐 - 共酰亚胺），特别是聚[偏苯三酸亚胺 - L - 酪氨酸 - 共 - 癸二酸 - 共 - 1,3 - 双（羧苯氧基）丙烷]酸酐[聚（TMA - Tyr：SA：CPP）]。由于在其主链中掺入了免疫佐剂L - 酪氨酸，这些聚合物对于疫苗抗原的控释可能特别有意义。使用双乳液溶剂蒸发技术由多种聚合物组合物制备微球，并在体外测试它们提供模型蛋白牛血清白蛋白控释的能力。微球呈球形，表面光滑，包封了超过70％的蛋白质。通过改变包封的蛋白质量，相同组成聚合物的蛋白质释放速率可以从每月每毫克微球0.3微克变化到超过125微克。使用具有不同单体比例的聚合物可以放大这种效果。观察到蛋白质释放与聚合物重量损失之间存在密切相关性，表明释放机制主要受聚合物侵蚀控制。聚（TMA - Tyr：SA：CPP）微球中牛血清白蛋白的释放也对pH敏感，在高pH下增强，在酸性条件下降低。
