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

Research performed at:

1. Department of Pharmaceutics, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.

2. Department of Pathology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

3. Analytical division, Faculty of Chemistry, University of Mazandaran, Babolsar, Iran.

4. Pharmaceutics Research Laboratory, School of Life Sciences, University of Sussex, Brighton BN1 9QJ, UK.

5. Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.

The authors:

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

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.