Release of a model protein from biodegradable self assembled films for surface delivery applications.

Release of a model protein from biodegradable self assembled films for surface delivery applications.
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DOI:
10.1016/j.jconrel.2008.07.032
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发表时间:
2008-11-12
期刊:
Journal of controlled release : official journal of the Controlled Release Society
影响因子:
--
通讯作者:
Hammond PT
Hammond PT
中科院分区:
其他
文献类型:
--
作者:
Macdonald M;Rodriguez NM;Smith R;Hammond PT

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层层(LBL)膜具有多种特征,使其在药物输送方面具有吸引力,包括连续输送生长因子的可能性,然而,到目前为止,此类膜的蛋白质输送一直缺乏概念证明。在这里,由溶菌酶(一种模型蛋白质)和一种可水解性和生物相容性的合成聚阳离子构建的LBL聚电解质膜被证明能够释放出具有吸引力的治疗蛋白从植入的医疗设备的局部输送。在室温下,可在3周至3个月内实现符合幂定律或线性分布的毫克/厘米~2规模释放。在37℃时释放速率增加,符合从100天到5天的表面侵蚀释放机制。这一释放时间范围可以通过改变合成聚阳离子的降解性来调节,并且通过增加这种可降解聚酯的疏水性,可以在37℃下增加到34天的释放。从这些薄膜中释放的酶保留了80%-100%的功能,强调了温和的加工条件,容易保留脆弱的蛋白质功能。这些结果揭示了加入治疗性蛋白质来调节植入表面和它们接触的细胞之间的相互作用的许多可能性。
Layer-by-layer (LbL) films have multiple features which make them attractive for drug delivery including the possibility of sequential delivery of growth factors, however, to date, proof of concept has been lacking for protein delivery from such films. Here, LbL polyelectrolyte films constructed with lysozyme (a model protein) and a hydrolytically degradable and biocompatible synthetic polycation are shown to be capable of release attractive for the localized delivery of therapeutic proteins from implanted medical devices. Milligram/cm2 scale release with power law or linear profile can be achieved over 3 weeks to 3 months at room temperature. The release rate at 37°C increases in a way that is compatible with a surface erosion mechanism of release from 100 days to 5 days. This time scale of release can be tuned by changing the degradability of the synthetic polycation, and an increase to 34 days of release at 37°C is seen by increasing the hydrophobicity of this degradable polyester. The enzyme released from these films retains 80–100% functionality, underscoring the mild processing conditions that are apt to preserve fragile protein function. These results uncover many possibilities for incorporation of therapeutic proteins to modulate the interaction between implanted surfaces and the cells they contact.
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