新型水解可降解交联互穿聚合物网络（IPN）：一种用于管理米索前列醇控释和降解的高效混合体系。

Novel Hydrolytic Degradable Crosslinked Interpenetrating Polymeric Networks (IPNs): An Efficient Hybrid System to Manage the Controlled Release and Degradation of Misoprostol.

作者信息

Mehmood Yasir, Shahid Hira, Barkat Kashif, Arshad Numera, Rasul Akhtar, Uddin Mohammad N, Kazi Mohsin

机构信息

Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad P.O. Box 38000, Pakistan.

Riphah Institute of Pharmaceutical Sciences (RIPS), Riphah International University Faisalabad, Faisalabad P.O. Box 38000, Pakistan.

出版信息

Gels. 2023 Aug 29;9(9):697. doi: 10.3390/gels9090697.

DOI:10.3390/gels9090697

PMID:37754378

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10529051/

Abstract

PURPOSE

The goal of this study was to make pH-sensitive HPMC/Neocel C19-based interpenetrating polymeric networks (IPNs) that could be used to treat different diseases. An assembled novel carrier system was demonstrated in this study to achieve multiple functions such as drug protection and self-regulated release.

METHODS

Misoprostol (MPT) was incorporated as a model drug in hydroxyl-propyl-methylcellulose (HPMC)- and Neocel C19-based IPNs for controlled release. HPMC- and Neocel C19-based IPNs were fabricated through an aqueous polymerization method by utilizing the polymers HPMC and Neocel C19, the initiator ammonium peroxodisulfate (APS), the crosslinker methylenebisacrylamide (MBA), and the monomer methacrylic acid (MAA). An IPN based on these materials was created using an aqueous polymerization technique. Samples of IPN were analyzed using scanning electron microscopy (SEM), atomic force microscopy (AFM), differential scanning calorimetry (DSC), thermal analysis (TGA), and powder X-ray diffraction (PXRD). The effects of the pH levels 1.2 and 7.4 on these polymeric networks were also studied in vitro and through swelling experiments. We also performed in vivo studies on rabbits using commercial tablets and hydrogels.

RESULTS

The thermal stability measured using TGA and DSC for the revised formulation was higher than that of the individual components. Crystallinity was low and amorphousness was high in the polymeric networks, as revealed using powder X-ray diffraction (PXRD). The results from the SEM analysis demonstrated that the surface of the polymeric networks is uneven and porous. Better swelling and in vitro results were achieved at a high pH (7.4), which endorses the pH-responsive characteristics of IPN. Drug release was also increased in 7.4 pH (80% in hours). The pharmacokinetic properties of the drugs showed improvement in our work with hydrogel. The tablet MRT was 13.17 h, which was decreased in the hydrogels, and its AUC was increased from 314.41 ng h/mL to 400.50 ng h/mL in hydrogels. The blood compatibility of the IPN hydrogel was measured using different weights (100 mg, 200 mg, 400 mg, and 600 mg; 5.34%, 12.51%, 20.23%, and 29.37%, respectively).

CONCLUSIONS

As a result, IPN composed of HPMC and Neocel C19 was successfully synthesized, and it is now possible to use it for the controlled release of MPT.

摘要

目的

本研究的目标是制备基于pH敏感的羟丙基甲基纤维素（HPMC）/Neocel C19的互穿聚合物网络（IPN），可用于治疗不同疾病。本研究展示了一种组装的新型载体系统，以实现药物保护和自我调节释放等多种功能。

方法

将米索前列醇（MPT）作为模型药物掺入基于羟丙基甲基纤维素（HPMC）和Neocel C19的IPN中以实现控释。基于HPMC和Neocel C19的IPN通过水溶液聚合法制备，使用聚合物HPMC和Neocel C19、引发剂过二硫酸铵（APS）、交联剂亚甲基双丙烯酰胺（MBA）和单体甲基丙烯酸（MAA）。使用水溶液聚合技术制备基于这些材料的IPN。使用扫描电子显微镜（SEM）、原子力显微镜（AFM）、差示扫描量热法（DSC）、热分析（TGA）和粉末X射线衍射（PXRD）对IPN样品进行分析。还通过体外和溶胀实验研究了pH值1.2和7.4对这些聚合物网络的影响。我们还使用市售片剂和水凝胶对兔子进行了体内研究。

结果

使用TGA和DSC测量的修订配方的热稳定性高于各个组分。如粉末X射线衍射（PXRD）所示，聚合物网络中的结晶度低且无定形度高。SEM分析结果表明，聚合物网络的表面不均匀且多孔。在高pH值（7.4）下实现了更好的溶胀和体外结果，这证实了IPN的pH响应特性。在pH 7.4时药物释放也增加（数小时内释放80%）。我们使用水凝胶的研究中药物的药代动力学特性有所改善。片剂的平均滞留时间（MRT）为13.17小时，在水凝胶中有所降低，其曲线下面积（AUC）在水凝胶中从314.41 ng·h/mL增加到400.50 ng·h/mL。使用不同重量（100 mg、200 mg、400 mg和600 mg；分别为5.34%、12.51%、20.23%和29.37%）测量了IPN水凝胶的血液相容性。