Physical crosslinking modulates sustained drug release from recombinant silk-elastinlike protein polymer for ophthalmic applications.

Physical crosslinking modulates sustained drug release from recombinant silk-elastinlike protein polymer for ophthalmic applications.
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DOI:
10.1016/j.jconrel.2011.07.036
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发表时间:
2011-12-10
期刊:
Journal of controlled release : official journal of the Controlled Release Society
影响因子:
--
通讯作者:
Wu X
Wu X
中科院分区:
其他
文献类型:
--
作者:
Teng W;Cappello J;Wu X

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我们评估了光学透明重组丝弹性蛋白样蛋白聚合物 SELP-47K 薄膜的药物释放能力,以可持续地释放常见的眼部抗生素环丙沙星。研究了用乙醇或甲醇蒸汽处理以诱导不同密度的物理交联的载药 SELP-47K 薄膜的环丙沙星释放动力学。此外,载药蛋白质膜被嵌入蛋白质聚合物涂层中,以进一步延长药物的释放。载药 SELP-47K 薄膜释放环丙沙星长达 132 小时,具有接近一级的释放动力学。载药薄膜的聚合物涂层可延长药物释放长达 220 小时。从药物递送基质中释放的环丙沙星的抗菌活性不会因薄膜流延过程或乙醇或甲醇处理而受损。通过分析薄膜样品的物理性质,包括平衡溶胀、可溶部分、表面粗糙度和疏水性,阐明了药物释放的机制。此外,还通过 FTIR 和拉曼光谱分析了 SELP-47K 的构象及其在薄膜中的物理交联。基于三参数物理的模型准确地描述了在各种薄膜和包衣处理中观察到的释放速率,并将影响归因于薄膜的物理交联程度以及药物与聚合物网络的亲和力的增加。总之,这些结果表明光学透明的丝弹性蛋白样蛋白膜可能是新型眼科药物输送装置的有吸引力的候选材料。
We evaluated the drug release capability of optically transparent recombinant silk-elastinlike protein polymer, SELP-47K, films to sustainably deliver the common ocular antibiotic, ciprofloxacin. The ciprofloxacin release kinetics from drug-loaded SELP-47K films treated with ethanol or methanol vapor to induce different densities of physical crosslinking was investigated. Additionally, the drug-loaded protein films were embedded in a protein polymer coating to further prolong the release of the drug. Drug-loaded SELP-47K films released ciprofloxacin for up to 132 hours with near first-order release kinetics. Polymer coating of drug-loaded films prolonged drug release for up to 220 hours. The antimicrobial activity of ciprofloxacin released from the drug delivery matrices was not impaired by the film casting process or the ethanol or methanol treatments. The mechanism of drug release was elucidated by analyzing the physical properties of the film specimens, including equilibrium swelling, soluble fraction, surface roughness and hydrophobicity. Additionally, the conformation of the SELP-47K and its physical crosslinks in the films was analyzed by FTIR and Raman spectroscopy. A three-parameter physics based model accurately described the release rates observed for the various film and coating treatments and attributed the effects to the degree of physical crosslinking of the films and to an increasing affinity of the drug with the polymer network. Together, these results indicate that optically transparent silk-elastinlike protein films may be attractive material candidates for novel ophthalmic drug delivery devices.
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