Potential Enhancement of Metformin Hydrochloride in Lipid Vesicles Targeting Therapeutic Efficacy in Diabetic Treatment.

Emmanuel Chekwube Ossai,Benjamin Emenike Amadi,Audu Mumuni Momoh,Augustine Chidi Madueke,Obioma Uzoma Njoku,Martins Obinna Ogugofor,Charles Odilichukwu R Okpala,Chioma Assumpta Anosike

doi:10.3390/ijms22062852

Abstract

The potential enhancement of metformin hydrochloride (MH) loaded in lipid vesicles targeting therapeutic efficacy on alloxan-induced diabetic rats was investigated. This involved lipid vesicles formulated with homogenously distributed nano-sized particles by a novel integrated process of multiple emulsification by membrane and solvent evaporation. The average diameter of the water-in-oil (W1/O), W1/O/W2 emulsion droplets, and lipid vesicles was 192 nm, 52 µm, and 173 nm, respectively. The entrapment yield of metformin hydrochloride (MH) in the prepared lipid vesicles was 40.12%. The metformin hydrochloride-loaded lipid vesicles (MH-LLVs) sustained the release of the entrapped drug over a 12-h period and reduced the plasma glucose level of diabetic rats by 77.4% compared with free MH solution (2-h period and 58.2%, respectively) after one week post-diabetic treatment through oral administration of MH-LLV and the free drug. The remarkable improvement in the biochemical parameters recorded in the MH-LLV-treated animals compared with those that received free MH solutions depicted an enhanced kidney function, liver function, as well as oxidative stress status. Pancreatic histology depicted a pancreas with intralobular ducts (ID) and exocrine secretory acini that characterize an intact pancreas, which suggests the ability of the MH-LLVs to restore pancreatic cells to normal, on a continued treatment. Overall, MH-LLV appears an encouraging extended-release formulation with enhanced bioavailability, sustained release, and improved antihyperglycemic potentials.

Highlights

Metformin hydrochloride (MH), in addition to its Food and Drug Administration (FDA) approval in the United States, is among the biguanide first-line drugs of choice for diabetes management [1,2]
Lipid vesicles entrapping metformin hydrochloride in high yield were prepared by multiple emulsification method, coupled with solvent evaporation
The increase in serum chloride and bicarbonate ions levels in metformin hydrochloride (MH)-LLV-treated animals relative to diabetic control animals as seen in this study suggests that the formulation enhances rehydration and may prevent metabolic acidosis

Summary

Introduction

Metformin hydrochloride (MH), in addition to its Food and Drug Administration (FDA) approval in the United States, is among the biguanide first-line drugs of choice for diabetes management [1,2]. MH delivers key functions such as facilitating the decrease in hepatic glucose output as well as supporting/upregulating the insulin-engineered glucose uptake by cells. It can diminish the absorption of glucose in the gut and downregulate the plasma concentration of free fatty acids, thereby cutting down the amount of substrate available for glucose production from non-carbohydrate sources [4]. It can perform as an insulin-sensitizing agent. The bioavailability of MH appears relatively low at about 50–60% [5] after oral administration, with urinary excretion of 30% to 50% of the unchanged form of the drug, while about 30% is removed in feces within 24 h [6]

Methods

Discussion

Conclusion