PEGylated Lipid Nanocontainers Tailored with Sunseed-Oil-Based Solidified Reverse Micellar Solution for Enhanced Pharmacodynamics and Pharmacokinetics of Metformin,Journal of Pharmaceutical Innovation

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PEGylated Lipid Nanocontainers Tailored with Sunseed-Oil-Based Solidified Reverse Micellar Solution for Enhanced Pharmacodynamics and Pharmacokinetics of Metformin
Journal of Pharmaceutical Innovation ( IF 2.7 ) Pub Date : 2022-05-12 , DOI: 10.1007/s12247-022-09654-w
Franklin Chimaobi Kenechukwu ₁ , Daniel Okwudili Nnamani ₁ , Bright Ugochukwu Nmesirionye ₁ , God’spower Tochukwu Isaac ₁ , Mumuni Audu Momoh ₁ , Anthony Amaechi Attama ₁

Affiliation

Purpose

Poor oral absorption, low bioavailability, short half-life, and gastrointestinal effects due to high dose of metformin required in the management of type-2 diabetes mellitus have spurred researchers to pay greater attention to the development of novel drug delivery systems to tackle these challenges. The aim of this study was to formulate and evaluate sunseed-oil-based PEGylated nanostructured lipid carriers (PEG-NLC) for enhanced delivery and prolonged antidiabetic activity of metformin.

Methods

The PEG-NLC and non-PEGylated NLC were formulated by high shear homogenization and thereafter characterized by scanning electron microscopy, mean particle size determination, photon correlation spectroscopy, differential scanning calorimetry (DSC), and Fourier transform infrared (FT-IR) spectroscopy. In vitro drug release, pharmacodynamic studies using alloxanized rat model, pharmacokinetics and safety evaluations were carried out. Results were compared with those of controls (market and pure samples of metformin).

Results

DSC results showed reduced crystallinity and hence greater possibility of enhanced drug solubility and entrapment, while FTIR results showed drug-excipient compatibility. The PEG-NLCs were safe, were stable spherical nanoparticles, had mean particle size, polydispersity indices and zeta potentials in the range of 290.6–880.6 nm, 0.494–0.625, and 26.1–32.8 mV, respectively. The PEG-NLCs showed enhanced drug release in simulated biorelevant media and prolonged antidiabetic activity compared with both non-PEGylated NLC and controls. Batch D₄₀ containing the highest amount of PEG-4000 (optimized formulation) gave sixfold increase in pharmacokinetics properties than marketed sample (Glucophage^®).

Conclusion

Sunseed-oil-based PEGylated NLC has proven to be a stable and safe carrier system for enhanced delivery and prolonged antidiabetic activity of metformin.

中文翻译：

使用基于葵花籽油的固化反向胶束溶液定制的聚乙二醇化脂质纳米容器，用于增强二甲双胍的药效学和药代动力学

目的

由于治疗 2 型糖尿病所需的高剂量二甲双胍导致口服吸收差、生物利用度低、半衰期短和胃肠道反应，这促使研究人员更加关注开发新型药物输送系统以应对这些挑战. 本研究的目的是制定和评估基于葵花籽油的 PEG 化纳米结构脂质载体 (PEG-NLC)，以增强二甲双胍的递送和延长抗糖尿病活性。

方法

PEG-NLC 和非 PEG 化 NLC 通过高剪切均质化配制，然后通过扫描电子显微镜、平均粒径测定、光子相关光谱、差示扫描量热法 (DSC) 和傅里叶变换红外 (FT-IR) 光谱进行表征。进行体外药物释放、使用四氧嘧啶大鼠模型的药效学研究、药代动力学和安全性评价。结果与对照组（市场和纯二甲双胍样品）的结果进行了比较。

结果

DSC 结果显示结晶度降低，因此增加了药物溶解度和截留的可能性，而 FTIR 结果显示药物-赋形剂相容性。PEG-NLC 是安全的，是稳定的球形纳米颗粒，平均粒径、多分散指数和 zeta 电位分别在 290.6-880.6 nm、0.494-0.625 和 26.1-32.8 mV 范围内。与非聚乙二醇化 NLC 和对照相比，PEG-NLC 在模拟生物相关介质中显示出增强的药物释放和延长的抗糖尿病活性。含有最高量 PEG-4000（优化配方）的批次 D _{40的药代动力学特性比市售样品（Glucophage}^®）提高了六倍。