Methylene blue-loaded niosome: preparation, physicochemical characterization, and in vivo wound healing assessment

Maryam Ghasemi,Ali Farmoudeh,Jafar Akbari,Neda Asemi,Ali Nokhodchi,Majid Saeedi

doi:10.1007/s13346-020-00715-6

Abstract

Following skin injury, the overproduction of reactive oxygen species (ROS) during the inflammatory phase can cause tissue damage and delay in wound healing. Methylene blue (MB) decreases mitochondrial ROS production and has antioxidant effects. The authors aimed to prepare MB-loaded niosomes using the ultra-sonication technique as a green formulation method. A Box–Behnken design was selected to optimize formulation variables. The emulsifier to cholesterol ratio, HLB of mixed surfactants (Span 60 and Tween 60), and sonication time were selected as independent variables. Vesicle size, zeta potential (ZP), and drug entrapment capacity percentage were studied as dependent variables. The optimized formulation of niosomes showed spherical shape with optimum vesicle size of 147.8 nm, ZP of − 18.0 and entrapment efficiency of 63.27%. FTIR study showed no observable interaction between MB and other ingredients. In vivo efficacy of optimized formulation was evaluated using an excision wound model in male Wistar rat. Superoxide dismutase (SOD, an endogenous antioxidant) and malondialdehyde (MDA, an end product of lipid peroxidation) levels in skin tissue samples were evaluated. After 3 days, MDA was significantly decreased in niosomal gel-treated group, whereas SOD level was increased. Histological results indicate rats that received niosomal MB were treated effectively faster than other ones.Graphical abstract

Highlights

Electronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.The cutaneous wound healing process is divided into four predictable phases: hemostasis, inflammation, proliferation, and maturation [1]
DL% was calculated for all formulations. This parameter shows the amount of drug loaded per unit weight of niosomes, and the results showed that DL was varied between 0 and 3.71 ± 0.11%
The relationship between the DL% and the independent variables is shown in the following mathematical model

Summary

Introduction

The cutaneous wound healing process is divided into four predictable phases: hemostasis, inflammation, proliferation (growth of new tissue), and maturation (tissue remodeling) [1]. Inflammatory cells (neutrophils and monocytes) migrate into the injured tissue. These cells play an important role in defense against invasive microorganisms and secrete growth factors that are required for the proliferation phase [1, 2]. Inflammatory cells are important sources of reactive oxygen species (ROS) that can induce damage to the surrounding tissues by cross-linking of proteins and peroxidation of lipids [3]. ROS are important in the wound healing process, but the overproduction of these molecules causes oxidative stress, resulting in prolonged and impaired wound healing.

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