Due to poor bioavailability and chemical instability, the effectiveness of curcumin is negligible in the treatment of numerous diseases. Solid lipid nanoparticles (SLNs) increase the bioavailability of lipophilic compounds and protect the drug from gastrointestinal degradation. The objective of our study is the utilization of SLNs to improve the pharmacokinetics and pharmacodynamics of curcumin in the management of diabetes mellitus. Central composite design was used to prepare curcumin-loaded SLNs (Cur-SLN). The analysis of independent variables like drug concentration, lipid concentration, and surfactant concentration was carried out using analysis of variance (ANOVA) to obtain the optimized batch (optimized Cur-SLN) having the desired values of dependent variables particle size and entrapment efficiency. In vitro release, differential scanning calorimeter (DSC), transmission electron microscopy (TEM), and Fourier Transform Infra-Red (FTIR) studies of optimized Cur-SLN were carried out and then its pharmacokinetic and pharmacodynamic studies were performed. The model was found to be significant for particle size and entrapment efficiency based on F-value and p-value. The optimized batch's predicted values were in close agreement with the actual values of particle size and entrapment efficiency. TEM results confirm mono-dispersion and spherical shape of particles in the formulation. The DSC results confirmed the changing of drug from crystalline to amorphous form. Burst release followed by the sustained release was obtained in the in vitro release studies. The pharmacokinetic study shows enhanced bioavailability of optimized Cur-SLN compared with a plain drug suspension. The optimized Cur-SLN achieved higher antidiabetic activity in streptozotocin-induced diabetes mellitus rats than the plain drug suspension. SLNs can be used as a promising technique for delivering curcumin in the management of diabetes mellitus.

中文翻译：

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姜黄素固体脂质纳米颗粒在链脲佐菌素诱导的糖尿病治疗中的药代动力学和药效学：中心复合设计的应用

由于生物利用度差和化学不稳定性，姜黄素在治疗多种疾病方面的有效性可以忽略不计。固体脂质纳米颗粒 (SLN) 可提高亲脂性化合物的生物利用度并保护药物免受胃肠道降解。我们研究的目的是利用 SLN 来改善姜黄素在糖尿病治疗中的药代动力学和药效学。中心复合设计用于制备加载姜黄素的前哨淋巴结（Cur-SLN）。使用方差分析 (ANOVA) 对自变量（如药物浓度、脂质浓度和表面活性剂浓度）进行分析，以获得具有所需因变量粒径和截留效率值的优化批次（优化 Cur-SLN）。体外对优化后的 Cur-SLN 进行了差示扫描量热仪 (DSC)、透射电子显微镜 (TEM) 和傅立叶变换红外 (FTIR) 研究，然后对其药代动力学和药效学进行了研究。基于F值和p值，发现该模型对于粒度和截留效率是显着的。优化批次的预测值与粒度和截留效率的实际值非常一致。TEM 结果证实了配方中颗粒的单分散和球形。DSC 结果证实了药物从结晶形式变为无定形形式。在体外获得爆释后缓释发布研究。药代动力学研究表明，与普通药物混悬液相比，优化的 Cur-SLN 的生物利用度更高。优化后的 Cur-SLN 在链脲佐菌素诱导的糖尿病大鼠中比普通药物悬浮液具有更高的抗糖尿病活性。SLNs 可用作在糖尿病管理中传递姜黄素的有前途的技术。