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两亲性聚氨酯水凝胶作为智能载体用于酸性疏水性药物。

Amphiphilic polyurethane hydrogels as smart carriers for acidic hydrophobic drugs.

机构信息

Institute of Chemistry, University of Campinas (UNICAMP), P.O. Box 6154, 13083-970 Campinas, SP, Brazil.

Institute of Chemistry, University of Campinas (UNICAMP), P.O. Box 6154, 13083-970 Campinas, SP, Brazil.

出版信息

Int J Pharm. 2018 Jul 30;546(1-2):106-114. doi: 10.1016/j.ijpharm.2018.05.034. Epub 2018 May 14.

Abstract

Amphiphilic hydrogels are widely reported as systems with great potential for controlled drug release. Nevertheless, the majority of studies make use of functionalization or attachment of drugs to the polymer chains. In this study, we propose a strategy of combining amphiphilic polyurethanes with pH-responsive drugs to develop smart drug carriers. While the amphiphilic character of the polymer imparts an efficient load of hydrophobic and hydrophilic drugs, the drug's characteristics determine the selectivity of the medium delivery. Drug loading and release behavior as well as hydrolytic degradation of chemically crosslinked polyurethane hydrogels based on PEG and PCL-triol (PU (polyurethane) hydrogels) synthesized by an easy one-pot route were studied. PU hydrogels have been shown to successfully load the hydrophobic acidic drug sodium diclofenac, reaching a partition coefficient of 8 between the most hydrophobic PU and diclofenac/ethanol solutions. Moreover, an oral administration simulation was conducted by changing the environment from an acidic to a neutral medium. PU hydrogels release less than 5% of the drug in an acidic medium; however, in a PBS pH 7.4 solution, diclofenac is delivered in a sustained fashion for up to 40 h, achieving 80% of cumulative release.

摘要

两亲水凝胶被广泛报道为具有巨大潜力的控制药物释放系统。然而,大多数研究都利用药物的功能化或附着到聚合物链上。在这项研究中,我们提出了一种将两亲性聚氨酯与 pH 响应性药物结合的策略,以开发智能药物载体。虽然聚合物的两亲特性赋予了疏水性和亲水性药物的有效负载,但药物的特性决定了介质传递的选择性。通过简单的一锅法合成了基于 PEG 和 PCL-三醇的两亲性聚氨酯(PU)水凝胶,研究了其化学交联的 PU 水凝胶的药物负载和释放行为以及水解降解。PU 水凝胶已成功负载疏水性酸性药物双氯芬酸钠,在最疏水的 PU 与双氯芬酸钠/乙醇溶液之间达到 8 的分配系数。此外,通过将环境从酸性变为中性介质,进行了口服给药模拟。在酸性介质中,PU 水凝胶释放的药物不到 5%;然而,在 PBS pH 7.4 溶液中,双氯芬酸钠以持续的方式释放长达 40 小时,达到 80%的累积释放。

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