Enhanced circulation longevity and pharmacodynamics of metformin from surface-modified nanostructured lipid carriers based on solidified reverse micellar solutions

Metformin hydrochloride (MTH) has been associated with poor/incomplete absorption (50–60%), low bioavailability, short half-life (0.4–0.5 h), high dosage and dose-related side effects. To overcome these barriers and improve oral bioavailability and efficacy of MTH, surface-modified nanostructured lipid carriers (NLCs) were developed. Lipid matrices composed of rational blends of beeswax and Phospholipon® 90H (as solid lipids) and Capryol-PGE 860 (as liquid lipid) were prepared by fusion, and the resultant lipid matrices were PEGylated to give 10, 20 and 40% PEGylated lipid matrices.

MTH-loaded non-PEGylated and PEGylated NLCs were prepared via high-shear hot homogenization and characterized regarding particle properties and physicochemical performance. The encapsulation efficiencies (EE%) and loading capacities (LC) of the MTH-loaded NLCs were determined while the in vitro drug release was evaluated in phosphate buffered saline (PBS, pH 7.4). Antidiabetic and pharmacokinetics properties of the NLCs were ascertained in an alloxan-induced diabetic rats model after oral administration. The MTH-loaded NLCs were nanomeric (particle size: 184.8–882.50 nm) with low polydispersity index (0.368–0.687) and zeta potential (26.5–34.2 mV), irregular shape, amorphous nature with reduced crystallinity.

The EE% and LC were >90 % and 16%, respectively. The formulations showed >65 % release over 12 h in a greater sustained manner than marketed MTH formulation (Glucophage®) as well as enhanced pharmacokinetics properties and sustained blood glucose lowering effect, even at reduced doses with PEGylated NLCs than Glucophage®. Thus, PEGylated NLC is a promising approach for improved delivery and oral bioavailability of MTH thus encouraging further development of the formulation.

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Materials: The pure sample of metformin used was obtained as a gift from May and Baker PLC (Ikeja, Lagos State, Nigeria). Phospholipon® 90H (P90H) (Phospholipid GmbH, Köln, Germany), sorbitol (Caesar & Loretz, Hilden, Germany), sorbic acid (Foodchem Int. Co., China), polyethylene glycol 4000 (PEG 4000) (Ph. Eur. Carl Roth GmbH + Co. KG Karlsruhe, Germany), beeswax (Carl Roth, Karlsruhe, Germany), Polysorbate 80 (Tween® 80) (Acros Organics, Geel, Belgium), Capryol-PGE 860 (Gattefossé, Saint – Priest Cedex, France), Glucophage® purchased from model pharmacy University of Nigeria, Nsukka (Merck KGaA, Darmstadt, Germany), Alloxan (Merck KGaA, Darmstadt, Germany) and double distilled water (Lion water, University of Nigeria, Nsukka, Nigeria) and other solvents and reagents were used as procured from their manufacturers without further purification. Adult albino Wistar rats of both sexes were procured from the Faculty of Veterinary Medicine, University of Nigeria, Nsukka, Nigeria.

Article information: Franklin Chimaobi Kenechukwu, God’spower Tochukwu Isaac, Daniel Okwudili Nnamani, Mumuni Audu Momoh, Anthony Amaechi Attama, Enhanced circulation longevity and pharmacodynamics of metformin from surface-modified nanostructured lipid carriers based on solidified reverse micellar solutions, Heliyon, Volume 8, Issue 3, 2022, ISSN 2405-8440, https://doi.org/10.1016/j.heliyon.2022.e09100.