Weiner Ashley A, Bock Eileen A, Gipson Margaret E, Shastri V Prasad
Department of Biomedical Engineering, Vanderbilt University, 5824 Stevenson Center, Nashville, TN 37232, USA.
Biomaterials. 2008 May;29(15):2400-7. doi: 10.1016/j.biomaterials.2008.01.013. Epub 2008 Mar 4.
Injectable delivery systems are attractive as vehicles for localized delivery of therapeutics especially in the context of regenerative medicine. In this study, the potential of photocrosslinked polyanhydride (PA) networks as an encapsulation matrix for long-term delivery of macromolecules was studied. The in vitro release of two model proteins (horseradish peroxidase (HRP) and bovine serum albumin labeled with fluorescein isothiocyanate (FITC-BSA)) was evaluated from crosslinked networks composed of sebacic acid dimethacrylate (MSA), 1,6-bis-carboxyphenoxyhexane dimethacrylate (MCPH), and poly(ethylene glycol) diacrylate (PEGDA), supplemented with calcium carbonate. Prior to incorporation into the networks, proteins were formulated by dilution in a cyclodextrin excipient followed by gelatin-based wet granulation. Protein release was quantified by activity assay (HRP) or fluorescence (FITC-BSA). Each protein was readily released from the networks with a unique release behavior. Most importantly, release of protein with retention of activity was achieved for durations ranging from 1 week to 4 months. The released HRP was additionally visualized using SDS-PAGE. In general, a more hydrophobic network resulted in slower rates of protein release. Incorporation of PEGDA into the matrices was critical for maintenance of integrity during degradation. These results suggest that this system may be useful as an injectable delivery system for long-term delivery of macromolecules.
注射给药系统作为治疗药物局部给药的载体很有吸引力，尤其是在再生医学领域。在本研究中，研究了光交联聚酸酐（PA）网络作为大分子长期给药的包封基质的潜力。从由癸二酸二甲基丙烯酸酯（MSA）、1,6-双羧基苯氧基己烷二甲基丙烯酸酯（MCPH）和聚乙二醇二丙烯酸酯（PEGDA）组成并添加碳酸钙的交联网络中评估了两种模型蛋白（辣根过氧化物酶（HRP）和异硫氰酸荧光素标记的牛血清白蛋白（FITC-BSA））的体外释放。在掺入网络之前，通过在环糊精赋形剂中稀释然后基于明胶的湿法制粒来配制蛋白质。通过活性测定（HRP）或荧光（FITC-BSA）对蛋白质释放进行定量。每种蛋白质都能以独特的释放行为从网络中轻松释放出来。最重要的是，在1周至4个月的时间内实现了具有活性保留的蛋白质释放。使用SDS-PAGE额外观察了释放的HRP。一般来说，疏水性更强的网络导致蛋白质释放速率更慢。将PEGDA掺入基质中对于降解过程中维持完整性至关重要。这些结果表明，该系统可能作为大分子长期给药的注射给药系统有用。
