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基于金属有机框架平台的生物相容性药物递送系统用于难溶性药物诺氟沙星的持续和控释

Biocompatible Drug Delivery System Based on a MOF Platform for a Sustained and Controlled Release of the Poorly Soluble Drug Norfloxacin.

作者信息

Yadav Preety, Kumari Sarita, Yadav Anand, Bhardwaj Priya, Maruthi Mulaka, Chakraborty Anindita, Kanoo Prakash

机构信息

Department of Chemistry, School of Basic Sciences, Central University of Haryana, Jant-Pali, Mahendergarh 123031, Haryana, India.

Department of Biochemistry, School of Interdisciplinary and Applied Sciences, Central University of Haryana, Jant-Pali, Mahendergarh 123031, Haryana, India.

出版信息

ACS Omega. 2023 Jul 27;8(31):28367-28375. doi: 10.1021/acsomega.3c02418. eCollection 2023 Aug 8.

DOI:10.1021/acsomega.3c02418
PMID:37576664
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10413448/
Abstract

Norfloxacin (NFX), an important antibacterial fluoroquinolone, is a class IV drug according to the biopharmaceutics classification system (BCS) and has low solubility and permeability issues. Such poor physicochemical properties of drug molecules lead to poor delivery and are of serious concern to the pharmaceutical industry for clinical development. We present here a conceptually new approach to deliver NFX, by loading the drug molecule on the porous platform of a biocompatible metal-organic framework (MOF), MIL-100(Fe). The loading of the drug on the MOF leading to NFX@MIL-100(Fe) was characterized by Fourier transform infrared (FTIR), UV-visible spectroscopy, thermogravimetric analyses (TGA), and nitrogen adsorption studies. Controlled experiments resulted in the high loading of the drug molecule (∼20 wt %) along with the desired sustained release. We could further control the release of norfloxacin by coating drug-loaded MIL-100(Fe) with PEG, PEG{NFX@MIL-100(Fe)}. Both drug delivery systems (DDSs), NFX@MIL-100(Fe) and PEG{NFX@MIL-100(Fe)}, were tested for their biocompatibility through toxicity studies. The DDSs are biocompatible and show insignificant cytotoxicity, as revealed by cell viability studies through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.

摘要

诺氟沙星（NFX）是一种重要的氟喹诺酮类抗菌药物，根据生物药剂学分类系统（BCS）属于IV类药物，存在溶解度低和渗透性差的问题。药物分子如此不佳的物理化学性质导致给药效果不佳，这是制药行业在临床开发中极为关注的问题。我们在此提出一种概念上全新的诺氟沙星给药方法，即将药物分子负载在生物相容性金属有机框架（MOF）MIL-100(Fe)的多孔平台上。通过傅里叶变换红外光谱（FTIR）、紫外可见光谱、热重分析（TGA）和氮气吸附研究对药物负载到MOF上形成NFX@MIL-100(Fe)进行了表征。对照实验实现了药物分子的高负载量（约20 wt%）以及预期的缓释效果。我们可以通过用聚乙二醇（PEG）包覆负载药物的MIL-100(Fe)，即PEG{NFX@MIL-100(Fe)}，进一步控制诺氟沙星的释放。通过毒性研究对两种药物递送系统（DDS），即NFX@MIL-100(Fe)和PEG{NFX@MIL-100(Fe)}的生物相容性进行了测试。细胞活力研究通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）法进行，结果表明这些DDS具有生物相容性且细胞毒性不显著。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/504a/10413448/c629cfeb65fd/ao3c02418_0010.jpg
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