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

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.

Niosomal Drug Delivery Systems for Ocular Disease—Recent Advances and Future Prospects

“…This study showed that MB-loaded niosome formulations had high encapsulation efficiency and acceptable stability. In addition, according to biochemical and macroscopic studies, the recovery rate of surgical wounds in the niosomal-treated group was higher than that of other groups [ 18 ].…”

The Efficacy of Cholesterol-Based Carriers in Drug Delivery

“…The healing of cutaneous wounds has four stages which are hemostasis, inflammation, proliferation and maturation [ 104 ]. Angiogenesis, which is the formation of new blood vessels, is an essential process during wound healing [ 105 ].…”

“…The body’s defense system releases endogenous antioxidant that helps against overexpression of ROS. A number of exogenous antioxidants such as phenolic compounds, ascorbic acid and vitamin E also speed up wound healing processes [ 104 ]. An ideal wound dressing needs to keep the wound moist, minimize infection, reduce pain and increase the rate of healing [ 106 ].…”

“…The optimized niosomal dispersion exhibited a controlled MB release rate with 26.897% of the drug released in the first hour compared to 45.064% of the free drug. In vivo results from the wounded male Wistar rats administered the MB (niosomal gel of free) transdermally showed significant wound closure when compared to those treated with placebo gel that was still open after 14 days [ 104 ]. The niosomal-gel treated wounds had thicker, organized collagen fibers with more fibroblasts and less inflammatory infiltrate compared to thin granulation tissue, disorganized collagen fibers and high number of inflammatory cells exhibited in free MB-treated and control rats.…”

“…The niosomal-gel treated wounds had thicker, organized collagen fibers with more fibroblasts and less inflammatory infiltrate compared to thin granulation tissue, disorganized collagen fibers and high number of inflammatory cells exhibited in free MB-treated and control rats. Niosomal gel-treated rats had significantly decreased malondialdehyde (MDA) and elevated Superoxide dismutase (SOD) levels only three days after surgery, but it took seven days for negative controls to reach the similar results [ 104 ]. Since SOD is an endogenous antioxidant and MDA is an end product of lipid peroxidation, the increase of the former and decrease of the latter showed the ability of niosomal gel in accelerating the rate of mitochondrial cytochrome c reduction thereby reducing the production free radicals in the mitochondria [ 112 ].…”