Work

Stable self-assembled oral metformin-bridged nanocochleates against hepatocellular carcinoma

Year: 2024

Type: article

Abstract: Despite its established anti-diabetic activity, Metformin hydrochloride (MET) has been repurposed for the management of hepatocellular carcinoma (HCC). Owing to MET high aqueous solubility and poor oral permeability, a novel nanoplatform is sought to overcome the current challenges of traditional formulations. In this study, we developed MET-bridged nanocochleates (MET-CO) using a direct bridging method followed by optimization and assessment using various in-vitro and in-vivo pharmacokinetic methods. The optimized nanocochleates MET-CO DCP 19, containing dicetyl phosphate (DCP), displayed uniform snail-shaped nano-rolls measuring 136.41 ± 2.11 nm with a PDI of 0.241 ± 0.005 and a highly negative ζ-potential of -61.93 ± 2.57 mV. With an impressive MET encochleation efficiency (> 75%), MET-CO DCP 19 exhibited a controlled biphasic release profile, with minimal initial burst followed by prolonged release for 24 h. Importantly, they showed significant MET permeation in both in-vitro Caco-2 and ex-vivo intestinal models compared to non-DCP containing formula or MET solution. The in-vivo oral bioavailability study demonstrated pronounced improvements in the pharmacokinetic parameters with a 5.5 relative bioavailability compared to MET solution. Notably, a significant reduction in IC 50 values in HepG2 cells after 24 h of treatment was observed. Furthermore, the optimized formulation showed a significant downregulation of anti-apoptotic and cancer stemness genes, with 12- and 2-fold lower expression compared to MET solution. These promising results highlight the efficacy of the novel MET-bridged nanocochleates as a stable nanoplatform for enhancing the oral bioavailability of MET and boosting its anticancer potential against HCC. Graphical Abstract

Source: Drug Delivery and Translational Research

DOI: 10.1007/s13346-024-01724-5

Authors: Mohamed G. El-Melegy, Amal H. El-Kamel, Radwa A. Mehanna, Ahmed Gaballah, Hoda M. Eltaher

Institution: Alexandria University

Language: English

Topic: Drug Solubulity and Delivery Systems

Subfield: Pharmaceutical Science

Field: Pharmacology, Toxicology and Pharmaceutics

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,390