Metformin hydrochloride and wound healing: from nanoformulation to pharmacological evaluation

J Liposome Res. 2019 Dec;29(4):343-356. doi: 10.1080/08982104.2018.1556291. Epub 2019 Jan 31.

Abstract

Niosomes as drug delivery systems have the ability to decrease drugs' side effects and increase their therapeutic effectiveness. Metformin HCl is an oral antihyperglycemic agent belonging to biguanides. It is the most commonly chosen drug as a startup therapy for patients newly diagnosed with type 2 diabetes. This study aims to encapsulate metformin HCl inside niosomes to be used as a transdermal formulation helping to prolong its antidiabetic effect and investigate its ability to enhance wound healing in diabetic patients. Thin film hydration method was used to prepare metformin HCl niosomes using different proportions of Span 60, Span 40, Tween 80, and cholesterol. All formulations were characterized using transmission electron microscope, zeta potential, and vesicle size. In vitro release studies, stability studies and in vivo evaluation were conducted on selected niosomal formulations. The results of entrapment efficiency ranged from 13% to 32%. Vesicle sizes were determined in nano-range. The in vitro release profile of metformin HCl from niosomes occurred in two consecutive phases. Biological evaluation on diabetic rats revealed that metformin HCl niosomal gel given every 2 days showed a better sustained antidiabetic effect than oral doses given daily. It also showed an improvement in wound healing for diabetic rats given metformin formulations compared to nontreated ones.

Keywords: Niosomes; diabetes; metformin HCl; transdermal delivery; wound healing.

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Blood Glucose / analysis
  • Cholesterol / chemistry
  • Delayed-Action Preparations / chemistry*
  • Diabetes Mellitus, Experimental
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Compounding / methods
  • Drug Liberation
  • Hexoses / chemistry
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / chemistry*
  • Liposomes / chemistry*
  • Male
  • Metformin / administration & dosage
  • Metformin / chemistry*
  • Nanocapsules / chemistry*
  • Polysorbates / chemistry
  • Rats, Wistar
  • Skin
  • Tissue Distribution
  • Wound Healing / drug effects*

Substances

  • Blood Glucose
  • Delayed-Action Preparations
  • Hexoses
  • Hypoglycemic Agents
  • Liposomes
  • Nanocapsules
  • Polysorbates
  • Metformin
  • Cholesterol
  • sorbitan monostearate