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® 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 β 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.

Graphical abstract

中文翻译：

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使用因子设计开发和优化pH敏感纳米颗粒用于口服格列齐特

背景

格列齐特是一种口服降血糖药，用于治疗非胰岛素依赖型糖尿病T2DM。格列齐特在胃中的溶解度低，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体内和受试者之间的变异性。

目的

这项研究的目的是开发，优化和评估基于Eudragit®S100聚合物的pH敏感纳米颗粒（NPs），用于口服递送格列齐特（GLZ），以尝试改善其吸收和生物利用度并减少其内部和内部的相互影响。 -受试者变异性。

方法

纳米沉淀技术用于制备GLZ NPs。采用33个全因子设计来研究独立变量（聚合物浓度，有机相体积和稳定剂浓度）对GLZ NP的平均粒径，ζ电位和掺入效率的影响。使用各种方法对开发的最佳制剂进行评估，包括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），药物溶解和葡萄糖刺激的胰岛素切片试验。

结果

结果分析表明，GLZ从结晶形式转变为非结构形式，并且GLZ与聚合物之间没有任何化学相互作用。体外药物释放取决于聚合物的溶解行为。葡萄糖刺激的胰岛素切片试验表明，在存在10 mM葡萄糖的情况下，将GLZ掺入NPs可以增强其对β细胞中胰岛素分泌的作用。

结论

我们的研究表明，优化的NP具有改善GLZ口服吸收的潜力。

图形概要