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基于含钠 Alginate 和壳聚糖包合物的 RSM-CCD 优化纳米复合材料中阿莫西林控释的比较评价。

Comparative Evaluation for Controlled Release of Amoxicillin from RSM-CCD-Optimized Nanocomposites Based on Sodium Alginate and Chitosan-Containing Inclusion Complexes.

机构信息

Polymer and Nanomaterial Lab, Department of Chemistry, Dr B R Ambedkar National Institute of Technology, Jalandhar 144011, Punjab, India.

出版信息

Mol Pharm. 2021 Oct 4;18(10):3795-3810. doi: 10.1021/acs.molpharmaceut.1c00340. Epub 2021 Sep 5.

DOI:10.1021/acs.molpharmaceut.1c00340
PMID:34482691
Abstract

Amoxicillin (AMX) is a semisynthetic antibiotic, an analogue of ampicillin, with a wide spectrum of bacterial activity against many microorganisms but possesses some limits. To increase the drug effectiveness, supramolecule nanocomposites composed of β-cyclodextrin (β-CD) and chitosan/sodium alginate/GO were chosen in the present study as a sustained release formulation. Nanocomposites of chitosan (CH), sodium alginate (ALG), and graphene oxide (GO) were synthesized at 50 °C. The inclusion complexes (ICs) were processed via the physical mixture (PM), kneading (KM), microwave (MW) method, or coprecipitation (CP) and directly loaded into the nanocomposite. To confirm the formation of true ICs, the ICs were analyzed by DSC, SEM, H NMR, 2D NMR ROESY, and XRD. A drug release study was performed to find out which method is best for the controlled release of drugs in different environments of pH 2, 7, and 7.4 at 37 °C. From the observed drug release data, it was found that PM and KM showed a burst release of drugs and the microwave method was the most suitable method to prepare exact ICs of AMX and β-CD for sustained release of drugs. Kinetics of drug release was analyzed by various kinetic models, and it was observed that the Korsmeyer-Peppas and Peppas-Sahlin models were best fit for drug release in all cases. A Phase solubility study was carried out to find the stoichiometry of IC formation and the complexation constant. The drug release was controlled and pH-dependent, confirming that nanocomposites are pH-sensitive. From drug release analysis, it was acknowledged that β-CD is capable of causing sustained drug release.

摘要

阿莫西林(AMX)是一种半合成抗生素,是氨苄青霉素的类似物,对许多微生物具有广泛的抗菌活性,但也存在一些局限性。为了提高药物的疗效,本研究选择了由β-环糊精(β-CD)和壳聚糖/海藻酸钠/GO 组成的超分子纳米复合材料作为缓释制剂。在 50°C 下合成壳聚糖(CH)、海藻酸钠(ALG)和氧化石墨烯(GO)的纳米复合材料。通过物理混合物(PM)、捏合(KM)、微波(MW)法或共沉淀(CP)直接将包含物复合物(IC)加工到纳米复合材料中。为了确认真正 IC 的形成,通过 DSC、SEM、H NMR、2D NMR ROESY 和 XRD 分析 IC。进行药物释放研究,以找出在不同 pH 值(2、7 和 7.4)和 37°C 下哪种方法最适合在不同环境中控制药物释放。从观察到的药物释放数据中可以发现,PM 和 KM 表现出药物的爆发释放,微波法是制备 AMX 和β-CD 精确 IC 以实现药物持续释放的最合适方法。通过各种动力学模型分析药物释放动力学,观察到在所有情况下,Korsmeyer-Peppas 和 Peppas-Sahlin 模型最适合药物释放。进行了相溶解度研究以确定 IC 形成的化学计量和络合常数。药物释放受 pH 控制且呈依赖性,这证实了纳米复合材料是 pH 敏感的。从药物释放分析中可以看出,β-CD 能够引起药物的持续释放。

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