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N-(9-芴甲氧羰基)-L-苯丙氨酸/纳米羟基磷灰石杂化超分子水凝胶作为具有抗菌性能和细胞相容性的药物输送载体。

N-(9-Fluorenylmethoxycarbonyl)-L-Phenylalanine/nano-hydroxyapatite hybrid supramolecular hydrogels as drug delivery vehicles with antibacterial property and cytocompatibility.

机构信息

College of Pharmacy, Hubei University of Chinese Medicine, 430065, Wuhan, China.

Key Laboratory of Chinese Medicine Resource and Compound Prescription, Ministry of Education, Hubei University of Chinese Medicine, 430065, Wuhan, China.

出版信息

J Mater Sci Mater Med. 2020 Jul 29;31(8):73. doi: 10.1007/s10856-020-06410-9.

DOI:10.1007/s10856-020-06410-9
PMID:32729101
Abstract

The intrinsic fragility of hydroxyapatite (HAP) restricts its wider applications for local delivery of antibiotics. The composites formed by integrating HAP with hydrogels can improve the properties of HAP. However, these reported composites not only require tedious preparation and employ organic solvent and toxic reagents, but also hardly have inherent antimicrobial property. In this study, N-(9-Fluorenylmethoxycarbonyl)-L-Phenylalanine/nano-hydroxyapatite (Fmoc-L-Phe/nHAP) hybrid supramolecular hydrogels with antibacterial property and cytocompatibility was prepared by integrating nHAP as reinforcement with Fmoc-L-Phe supramolecular hydrogels. The results showed that nHAP bounds in the chamber of the gel network and adheres to the fiber of Fmoc-L-Phe due to intermolecular interaction, remarkably improving the mechanical strength of Fmoc-L-Phe supramolecular hydrogels. The results of inhibition zone experiment and MTT experiment showed that the Fmoc-L-Phe/nHAP hybrid supramolecular hydrogels possess antimicrobial property and cytocompatibility. In vitro release experiment of chlorogenic acid (CGA) from the hybrid supramolecular hydrogels was performed. The study of the release kinetics indicated that the release behavior of CGA from the hybrid supramolecular hydrogels is following Weibull model and release mechanism involved Fickian diffusion and erosion of the surface of hydrogel matrix. The release of CGA shows a good inhibition effect on S. aureus. The results show that the Fmoc-L-Phe/nHAP hybrid hydrogels with antibacterial property and cytocompatibility have promising applications as drug delivery carrier. Due to the intrinsic fragility of hydroxyapatite (HAP), the properties of HAP could be improved by incorporation into hydrogels. However, these reported composites not only require tedious preparation and employ organic solvent and toxic reagents, but also hardly have inherent antimicrobial property. We prepared N-(9-Fluorenylmethoxycarbonyl)-L-Phenylalanine/nano-hydroxyapatite (Fmoc-L-Phe/nHAP) hybrid supramolecular hydrogels by integrating nHAP as reinforcement with Fmoc-L-Phe supramolecular hydrogels. The results showed that nHAP bounds in the chamber of the gel network and adheres to the fiber of Fmoc-L-Phe due to intermolecular interaction, remarkably improving the mechanical strength of Fmoc-L-Phe supramolecular hydrogels. The results of inhibition zone experiment and MTT experiment showed that the Fmoc-L-Phe/nHAP hybrid supramolecular hydrogels possess antibacterial property and cytocompatibility. In vitro release experiment of chlorogenic acid (CGA) from the hybrid supramolecular hydrogels was performed. The study of the release kinetics indicated that the release behavior of CGA from the hybrid supramolecular hydrogels is following Weibull model and release mechanism involved Fickian diffusion and erosion of the surface of hydrogel matrix. The release of CGA shows a good inhibition effect on S. aureus. The results show that the Fmoc-L-Phe/nHAP hybrid hydrogels with antibacterial property and cytocompatibility have promising applications as drug delivery carrier.

摘要

纳米羟基磷灰石/(9-芴甲氧羰基)-L-苯丙氨酸(Fmoc-L-Phe/nHAP)杂化超分子水凝胶具有抗菌性和细胞相容性,由整合纳米羟基磷灰石作为增强相与 Fmoc-L-Phe 超分子水凝胶制备而成。结果表明,由于分子间相互作用,nHAP 结合在凝胶网络的腔室中并粘附在 Fmoc-L-Phe 的纤维上,显著提高了 Fmoc-L-Phe 超分子水凝胶的机械强度。抑菌圈实验和 MTT 实验结果表明,Fmoc-L-Phe/nHAP 杂化超分子水凝胶具有抗菌性和细胞相容性。从杂化超分子水凝胶中进行绿原酸(CGA)的体外释放实验。释放动力学研究表明,CGA 从杂化超分子水凝胶中的释放行为遵循 Weibull 模型,释放机制涉及 Fickian 扩散和水凝胶基质表面的侵蚀。CGA 的释放对金黄色葡萄球菌表现出良好的抑制作用。结果表明,具有抗菌性和细胞相容性的 Fmoc-L-Phe/nHAP 杂化水凝胶作为药物载体具有广阔的应用前景。由于羟基磷灰石(HAP)固有脆性,可通过掺入水凝胶来改善 HAP 的性能。然而,这些报道的复合材料不仅需要繁琐的制备过程,使用有机溶剂和有毒试剂,而且几乎没有内在的抗菌性能。我们通过整合纳米羟基磷灰石作为增强相与 Fmoc-L-Phe 超分子水凝胶制备了 N-(9-芴甲氧羰基)-L-苯丙氨酸/纳米羟基磷灰石(Fmoc-L-Phe/nHAP)杂化超分子水凝胶。结果表明,由于分子间相互作用,nHAP 结合在凝胶网络的腔室中并粘附在 Fmoc-L-Phe 的纤维上,显著提高了 Fmoc-L-Phe 超分子水凝胶的机械强度。抑菌圈实验和 MTT 实验结果表明,Fmoc-L-Phe/nHAP 杂化超分子水凝胶具有抗菌性和细胞相容性。从杂化超分子水凝胶中进行绿原酸(CGA)的体外释放实验。释放动力学研究表明,CGA 从杂化超分子水凝胶中的释放行为遵循 Weibull 模型,释放机制涉及 Fickian 扩散和水凝胶基质表面的侵蚀。CGA 的释放对金黄色葡萄球菌表现出良好的抑制作用。结果表明,具有抗菌性和细胞相容性的 Fmoc-L-Phe/nHAP 杂化水凝胶作为药物载体具有广阔的应用前景。

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