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