<p>Novel Albumin Nanoparticle Enhanced the Anti-Insulin-Resistant-Hepatoma Activity of Metformin</p>

Abstract

Introduction: Metformin is an ideal candidate to treat the liver tumor with insulin resistance because of its good performance in the treatment of type 2 diabetes and the advantage in cancer therapy. We aim to develop a delivery system with higher efficiency than free drug. Methods: Metformin-bovine serum albumin (met-BSA) nanoparticles (NPs) were prepared using the anti-solvent precipitation method with a stabilizer of BSA for particle growth. The therapeutic effect of the drug was tested by the insulin-resistant HepG2 cells and C57BL/6J mice at a glucose starvation condition. The interaction mechanism of the drug and the protein during the formation of the NPs was tested using a series of spectroscopy. Results: Metformin and BSA formed nonporous and spherical particles of about 200 nm with proper lognormal distribution and thermostability. The cellular uptake, as well as the anti-liver cancer activities of met-BSA, was enhanced dramatically compared with the free drug. The thermodynamic studies suggested that the weak binding of metformin to BSA was governed by hydrogen bonds and van der Waals forces. Moreover, the results of synchronous, circular dichroism (CD) and three-dimensional fluorescence demonstrated that the BSA skeleton and chromophore microenvironments were changed in the presence of metformin. Conclusion: Therefore, met-BSA has been proved as a simple yet effective therapeutic agent for cancer with insulin resistance, promising for future clinic translations in cancer treatment.

Biochemical and histopathological evaluation of the effect of metformin and metformin nanoparticles against alloxan-induced diabetes in Rats

“…Higher ALT levels are a risk factor for type 2 diabetes, indicating a possible role for increased hepatic gluconeogenesis and inflammation in the pathogenesis of type 2 diabetes. Parallel to preceding data (Lu et al, 2020), the current study revealed liver destruction in diabetic rats treated with metformin and metformin nanoparticles were decreased by AST and ALT enzymes, but ALP was increased in metformin nanoparticles than others. Diabetic hyperglycemia raises plasma levels of urea, creatinine, and uric acid, important indicators of renal dysfunction (Khadre, et al,2011).…”

Rationalized landscape on protein-based cancer nanomedicine: Recent progress and challenges

“…In addition to these two specified drug-binding domains, HSA molecule exhibited other drug binding strategies including electrostatic interaction as well as hydrophobic interaction ( Iqbal et al, 2021 ; Wang et al, 2023 ). Various kinds of cytotoxic agents ( Zhang et al, 2018 ; Motevalli et al, 2019 ), anti-inflammatory agents ( Czub and Handing, 2020 ; Spada et al, 2021 ) hypoglycemic agents ( Lu et al, 2020 ; Jose et al, 2015 ), carbohydrates ( Wang et al, 2024 ) and other drugs ( Mickaela Martinez et al, 2022 ; Patel et al, 2022 )might have high affinity to bind to albumin, thereby improving their pharmacokinetics and therapeutic efficiencies with reduced adverse side effects. Usually, therapeutic drug molecules interact with albumin either through electrostatic, hydrophobic interaction or specific binding domain to generate albumin-drug conjugates or nanoparticles with nanometers size ( Hassanin and Elzoghby, 2020 ; Pal et al, 2023 ).…”

A Review on Drug Delivery System for Tumor Therapy

“…Studies have shown that MET has a high affinity to serum albumin (Rahnama et al, 2015;Leboffe et al, 2020). Thus, MET-BSA NPs have been prepared with the weak binding of MET to BSA governed by hydrogen bonds and van der Waals forces using the anti-solvent precipitation method, which is a more effective therapeutic agent for liver tumor with insulin resistance than free MET (Lu et al, 2020). NPs have also been used to verify the strong association between type II diabetes and (MiaPaCa-2) pancreatic carcinoma cell lines (Jose et al, 2015).…”