pH-Sensitive Nanoparticles Developed and Optimized Using Factorial Design for Oral Delivery of Gliclazide
pH-Sensitive Nanoparticles Developed and Optimized Using Factorial Design for Oral Delivery of Gliclazide
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DOI：
10.1007/s12247-021-09536-7
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发表时间：
2021-02-27
影响因子：
2.6
通讯作者：
Shelling, Andrew N.
中科院分区：
文献类型：
--
作者：
Al-Kassas, Raida;Madni, Asadullah;Shelling, Andrew N.
背景格列齐特是一种口服降糖药，用于治疗非胰岛素依赖型糖尿病2型糖尿病。格列齐特在胃中溶解度低，口服吸收和生物利用度差。格列齐特的pH依赖性溶解度影响受试者内和受试者间的变异性。目的本研究的目的是开发，优化和评估基于Eudragit（R）S100聚合物的pH敏感纳米粒（NP）用于口服格列齐特（GLZ），以改善其吸收和生物利用度，并减少其在体内和体内的释放。方法采用纳米沉淀法制备GLZ纳米粒。采用33完全析因设计研究了自变量（聚合物浓度、有机相体积和稳定剂浓度）对GLZ NPs的平均粒径、zeta电位和掺入效率的影响。采用X射线衍射（XRD）、差示扫描量热法（DSC）、傅里叶变换红外光谱（FT-IR）和扫描电子显微镜（SEM）等方法对所开发的最佳配方进行了评价，结果GLZ由结晶转变为非结构形式，且GLZ与胰岛素之间不存在任何化学相互作用。聚合物。体外药物释放依赖于聚合物的溶出行为。葡萄糖刺激的胰岛素切片实验表明，GLZ掺入纳米粒后，在10 mM葡萄糖存在下对β细胞胰岛素分泌的影响增强。结论优化的纳米粒具有改善GLZ口服吸收的潜力。
Background Gliclazide is an oral hypoglycaemic agent used for the treatment of non-insulin dependent diabetes mellitus T2DM. Gliclazide has low solubility in the stomach and poor oral absorption and bioavailability. The pH-dependent solubility of gliclazide influences the intra- and inter-subject variability.Purpose The purpose of this study was to develop, optimize and evaluate pH-sensitive nanoparticles (NPs) based on Eudragit (R) S100 polymer for oral delivery of gliclazide (GLZ) in an attempt to improve its absorption and bioavailability and to reduce its intra- and inter-subject variability.Methods Nanoprecipitation technique was used for preparation of GLZ NPs. A 33 full factorial design was applied to study the effect of independent variables (polymer concentration, volume of the organic phase and stabilizer's concentration) on the mean particle size, zeta potential and the incorporation efficiency of GLZ NPs. The developed optimal formulation was evaluated using various methods including X-ray diffraction (XRD), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM), drug dissolution and glucose stimulated insulin section test.Results The analysis of the results revealed transformation of GLZ from crystalline to unstructured form and the absence of any chemical interactions between GLZ and the polymer. The in vitro drug release was dependent on the dissolution behaviour of the polymer. The glucose-stimulated insulin section test showed that incorporation of GLZ into NPs has potentiated its effect on insulin secretion in beta cells in presence of 10 mM glucose.Conclusion Our study suggests that the optimized NPs have a potential to improve the oral absorption of GLZ.