Biodegradable Polyphosphazene Based Peptide-Polymer Hybrids
Biodegradable Polyphosphazene Based Peptide-Polymer Hybrids
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DOI：
10.3390/polym8040161
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发表时间：
2016-04-01
期刊：
影响因子：
5
通讯作者：
Teasdale, Ian
中科院分区：
文献类型：
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作者：
Linhardt, Anne;Koenig, Michael;Teasdale, Ian
通过用四肽Gly-Phe-Leu-Gly对聚磷腈主链进行宏观取代，设计了一系列可用于酶降解的新型多肽杂化聚合物。进一步将杂化聚合物与亲水性聚氧化亚烷基醚杰弗胺M-1000共取代，得到了可溶于水和可生物降解的杂化聚合物。通过P-31核磁共振波谱、动态光散射和场流动分级进行的详细降解研究表明，聚合物通过酶和水解途径相结合的方式降解。选择多肽序列是因为它的已知性质可以进行溶酶体降解；因此，这些可降解的、可溶于水的聚合物可能对用作聚合物疗法有重大兴趣。在此背景下，我们研究了免疫反应调节剂咪喹莫特通过四肽与聚合物的偶联，并报道了偶联物的自组装行为以及它在酶作用下引发的药物释放行为。
A novel series of peptide based hybrid polymers designed to undergo enzymatic degradation is presented, via macrosubstitution of a polyphosphazene backbone with the tetrapeptide Gly-Phe-Leu-Gly. Further co-substitution of the hybrid polymers with hydrophilic polyalkylene oxide Jeffamine M-1000 leads to water soluble and biodegradable hybrid polymers. Detailed degradation studies, via P-31 NMR spectroscopy, dynamic light scattering and field flow fractionation show the polymers degrade via a combination of enzymatic, as well as hydrolytic pathways. The peptide sequence was chosen due to its known property to undergo lysosomal degradation; hence, these degradable, water soluble polymers could be of significant interest for the use as polymer therapeutics. In this context, we investigated conjugation of the immune response modifier imiquimod to the polymers via the tetrapeptide and report the self-assembly behavior of the conjugate, as well as its enzymatically triggered drug release behavior.