Abstract
The present study aimed to formulate atorvastatin niosome (Atrosome) through an ultrasonic technique and to determine its contribution to the extent of wound healing in an animal model. The optimized Atrosome formulation (Atrosome-2) was stable at 4 °C for 3 months. Differential scanning calorimetry (DSC), ATR-Fourier transform infrared spectroscopy (ATR-FTIR), and powder X-ray diffraction (PXRD) analysis revealed that atorvastatin (ATR) was well encapsulated within the niosomes either in a stabilized amorphous form or a molecularly dispersed state. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), and atomic force microscope (AFM) confirmed the spherical nature of the Atrosomes. The optimized formulation showed polydispersity index, particle size, drug encapsulation efficiency (EE%), and zeta potential of 0.457 ± 0.05, 196.33 ± 6.45 nm, 86.15 ± 0.58 %, and − 20.73 ± 0.98 mV, respectively. ATR release from the Atrosome gel followed the first-order kinetic model and showed no cytotoxicity in the in vitro cytotoxicity test. Cell viability (human foreskin fibroblast cell line) was nearly 99%. An excision wound model was also applied in male Wistar rats to examine the in vivo efficacy of the optimized formulation, followed by investigating malondialdehyde (MDA, an end-product of lipid peroxidation), superoxide dismutase (SOD, an endogenous antioxidant), hydroxyproline levels, and glutathione peroxidase (GPx) in skin tissue samples. MDA significantly decreased in the Atrosome gel group after 21 days, while GPx, SOD, and hydroxyproline levels demonstrated an increase. According to histological results, rats receiving Atrosomes were treated effectively faster when compared to the other formulation used.
Highlights
The findings revealed that ATR had cytotoxicity effects on the Human foreskin fibroblast (HFF) normal cell line, while Atrosome presented no cytotoxicity effects, which is in agreement with the results of Çelik et al, who demonstrated an increase in cytotoxicity in human neuroblastoma cell lines (SHSY-5Y) in terms of various ATR concentrations [41]
The current study dealt with incorporating the atorvastatin (ATR) into niosomes made by combining cholesterol and nonionic surfactants
According to solid-state investigations, ATR in the niosome was in an amorphous state, and the interaction between ATR and other excipients used in the preparation of the niosomes was ruled out
Summary
Mazandaran University of Medical Sciences, Sari, Iran. 3 Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. 4 Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. 6 Cancer Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran. Wound healing is an essentially dynamic and biological procedure that contains four overlapping stages of hemostasis, inflammation, proliferation, and remodeling [1]. Oxidative reactions and inflammatory responses have important contributions to wound healing [4]. Some studies report that tissue injury heavily relies on calcium [5], which may have a noticeable contribution to wound healing while affecting the extracellular matrix secretion and F-actin organization in collagen bundles via fibroblasts at the wound area [6].
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