Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, 22060, Pakistan; Hamdard Institute of Pharmaceutical Sciences, Hamdard University, Islamabad Campus, Pakistan.
Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, 22060, Pakistan.
Int J Pharm. 2019 Oct 5;569:118557. doi: 10.1016/j.ijpharm.2019.118557. Epub 2019 Aug 1.
This study describes the fabrication of chemically crosslinked pectin-based LA-co-MAA hydrogels through free radical polymerization technique for the colonic delivery of oxaliplatin. Methylene bisacrylamide was used as a crosslinking agent and ammonium persulfate as an initiator. The successful fabrication and drug loading were confirmed through Fourier transform infrared spectroscopy (FTIR). The thermal investigations through differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) suggested the higher thermal stability of the unloaded and OXP-loaded formulations as compared to the raw materials. X-ray diffraction (XRD) analysis showed a decrease in crystallinity after crosslinking. The swelling, drug loading, and drug release were increased with an increase in the concentration of pectin and lactic acid (LA) while methacrylic acid (MAA) displayed an inverse behavior. The in-vitro biodegradability was evaluated against lysozyme and collagenase. The results showed that the hydrogels were stable against blank PBS as compared to lysozyme and collagenase. MTT-assay proved that the blank hydrogels were cytocompatible while free OXP and OXP-loaded hydrogels displayed dose-dependent effect against Vero, MCF-7, and HCT-116 cell lines. The oral tolerability study in rabbits confirmed that the hydrogel dispersion was well-tolerable up to 3650 mg/kg of body weight without causing any histopathological or hematological changes when compared with the control group.
本研究通过自由基聚合技术制备了化学交联的果胶基 LA-co-MAA 水凝胶，用于奥沙利铂的结肠递药。亚甲基双丙烯酰胺用作交联剂，过硫酸铵用作引发剂。傅里叶变换红外光谱（FTIR）证实了成功的制备和药物负载。差示扫描量热法（DSC）和热重分析（TGA）的热研究表明，与原材料相比，未负载和 OXP 负载制剂具有更高的热稳定性。X 射线衍射（XRD）分析表明交联后结晶度降低。随着果胶和乳酸（LA）浓度的增加，溶胀、药物负载和药物释放增加，而甲基丙烯酸（MAA）则表现出相反的行为。用溶菌酶和胶原酶评价体外生物降解性。结果表明，与溶菌酶和胶原酶相比，水凝胶在空白 PBS 中更稳定。MTT 测定证明空白水凝胶具有细胞相容性，而游离 OXP 和 OXP 负载水凝胶对 Vero、MCF-7 和 HCT-116 细胞系表现出剂量依赖性作用。在兔子中的口服耐受性研究证实，与对照组相比，水凝胶分散体在高达 3650mg/kg 体重时耐受性良好，不会引起任何组织病理学或血液学变化。
