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载药 PCL@MOF 薄膜的研制及其在光聚合容器中的缓释性能。

Development of Drug-Loaded PCL@MOF Film Enclosed in a Photo Polymeric Container for Sustained Release.

机构信息

Joint Department of Biomedical Engineering, North Carolina State University, Raleigh, North Carolina 27695-7907, United States.

Department of Materials Science and Engineering, North Carolina State University, Raleigh, North Carolina 27695-7907, United States.

出版信息

ACS Appl Bio Mater. 2024 Aug 19;7(8):5382-5396. doi: 10.1021/acsabm.4c00564. Epub 2024 Jul 11.

DOI:10.1021/acsabm.4c00564
PMID:38992948
Abstract

The programmed fabrication of oral dosage forms is associated with several challenges such as controlled loading and disintegration. To optimize the drug payload, excipient breakdown, and site-specific sustained release of hydrophobic drug (sulfamethoxazole, SM), we propose the development of acrylate polymer tablets enclosed with drug-loaded polycaprolactone (PCL) films. The active pharmaceutical ingredient (API) is physisorbed into the porous iron (Fe)-based metal-organic framework (MOF) and later converted to tangible PCL films, which, upon folding, are incorporated into the acrylate polymer matrices (P1/P2/P3). X-ray powder diffraction (XRPD) analysis and scanning electron microscopy (SEM) micrographs confirmed the stability and homogeneous distribution of MOF within the 50 μm thick film. Adsorption-desorption measurements at ambient temperatures confirmed the decrease in the BET surface area of PCL films by 40%, which was ∼3.01 m/g, and pore volume from 30 to 9 nm. The decrease in adsorption and surface parameters could confirm the gradual accessibility of SM molecules once exposed to a degrading environment. Fourier transform infrared (FTIR) analyses of in vitro dissolution confirmed the presence of the drug in the MOF-PCL film-enclosed tablets and concluded the cumulative SM release at pH ∼ 8.2 which followed the order SM@Fe-MOF < P1/P2/P3 < PCL-SM@Fe-MOF < P1/PCL-SM@Fe-MOF < P3/PCL-SM@Fe-MOF. The results of the study indicate that the P3/PCL-SM@Fe-MOF assembly has potential use as a biomedical drug delivery alternative carrier for effective drug loading and stimuli-responsive flexible release to attain high bioavailability.

摘要

口服剂型的程序制造与许多挑战相关,例如控制负载和崩解。为了优化药物载药量、赋形剂崩解和疏水性药物(磺胺甲噁唑,SM)的局部持续释放,我们提出了开发用载药聚己内酯(PCL)薄膜包裹的丙烯酸酯聚合物片的方案。活性药物成分(API)物理吸附到多孔铁(Fe)基金属有机骨架(MOF)中,然后转化为有形的 PCL 薄膜,在折叠后将其纳入丙烯酸酯聚合物基质(P1/P2/P3)中。X 射线粉末衍射(XRPD)分析和扫描电子显微镜(SEM)显微照片证实了 MOF 在 50μm 厚薄膜内的稳定性和均匀分布。在环境温度下的吸附-解吸测量证实了 PCL 薄膜的 BET 比表面积减少了 40%,约为 3.01m/g,孔体积从 30 到 9nm 减少。吸附和表面参数的减少可以证实一旦暴露于降解环境,SM 分子的逐渐可及性。体外溶解的傅里叶变换红外(FTIR)分析证实了 MOF-PCL 薄膜包裹的片剂中存在药物,并得出了在 pH∼8.2 时 SM 的累积释放遵循 SM@Fe-MOF< P1/P2/P3< PCL-SM@Fe-MOF< P1/PCL-SM@Fe-MOF< P3/PCL-SM@Fe-MOF 的顺序。研究结果表明,P3/PCL-SM@Fe-MOF 组装体具有作为生物医学药物输送替代载体的潜力,可有效负载药物并对刺激作出响应,以实现高生物利用度。

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