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

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Abstract

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.

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Funding

This research work received financial support from the Tertiary Education Trust Fund (TETFund) (Grant no. TETFUND/DR&D/CE/NRF/2019/STI/46/) by Government of Nigeria. Dr. Franklin C. Kenechukwu wishes to acknowledge Phospholipid GmbH, Köln, Germany, for generous provision of Phospholipon® 90H (P90H), Ph. Eur. Carl Roth GmbH + Co. KG Karlsruhe, Germany, for the king gift of polyethylene glycol 4000 (PEG 4000) and beeswax.

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Authors and Affiliations

  1. Drug Delivery and Nanomedicines Research Group, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Nigeria, Enugu State, 410001, Nigeria

    Franklin Chimaobi Kenechukwu, Daniel Okwudili Nnamani, Bright Ugochukwu Nmesirionye, God’spower Tochukwu Isaac, Mumuni Audu Momoh & Anthony Amaechi Attama

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  1. Franklin Chimaobi Kenechukwu
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  2. Daniel Okwudili Nnamani
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Contributions

Franklin Chimaobi Kenechukwu did conceptualization, supervision, methodology, validation, resources, funding acquisition, writing—original and draft as well as revision; Daniel Okwudili Nnamani performed methodology, writing—original and draft as well as revision; Bright Ugochukwu Nmesirionye was involved in methodology, formal analysis, investigation, writing—review and editing; God’spower Tochukwu Isaac contributed to methodology and writing—review and editing; Mumuni Audu Momoh and Anthony Amaechi Attamadone methodology, validation, resources, supervision, writing—review and editing.

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Correspondence to Franklin Chimaobi Kenechukwu.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All experimental protocols were conducted with strict adherence to the guidelines of the Institutional Animal Care and Use Committee of the University of Nigeria, Nsukka. Ethical clearance approval for in vivo antidiabetic studies was sought and obtained from the Faculty of Pharmaceutical Sciences Research Ethics Committee (UNN/FPS/2019-2020_017X) before the commencement of the in vivo animal studies.

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Kenechukwu, F.C., Nnamani, D.O., Nmesirionye, B.U. et al. PEGylated Lipid Nanocontainers Tailored with Sunseed-Oil-Based Solidified Reverse Micellar Solution for Enhanced Pharmacodynamics and Pharmacokinetics of Metformin. J Pharm Innov 18, 437–460 (2023). https://doi.org/10.1007/s12247-022-09654-w

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