Fatemeh Najafpour - School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Sepideh Arabzadeh - Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
Fatemeh Kalalinia - Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
Neda Mostajeran - Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
Seyed Mohsen Laal Mousavi - Department of Health Information Technology, Faculty of Paramedical Science, Mashhad University of Medical Sciences, Mashhad, Iran
Reavan Yazdian-Robati - Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
Ezzat Hashemi - Department of Neurology and Neurological Science, Stanford University, Stanford, CA, US
Maryam Hashemi - Departments of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad, University of Medical Sciences, Mashhad, Iran

Objective(s): Wound healing is one of the most fundamental issues in medical science. Solanum nigrum L. has been attracted great attention for its antioxidant, antimicrobial and anti-inflammatory activities. The aim of this study was to evaluate the effect of leaf extract of S. nigrum L-loaded sodium alginate nanoparticles (NPs) embedded in chitosan hydrogel on wound healing.Materials and Methods: Ethanolic extract of S. nigrum L. leaves (۵% v/v) were loaded into sodium alginate NPs using the ionic gelation technique and characterized (Ext-AG NPs). Then, NPs were incorporated into chitosan hydrogel (Ext-AG-CS hydrogel) and the properties of this formulation such as viscosity and release profile were evaluated. The antimicrobial activity of the extract alone and loaded into the hydrogel (Ext-CS hydrogel) was measured on the Staphylococcus aureus, Pseudomonas aeruginosa and Bacillus subtilius by MIC assay. Finally, their wound healing effects were studied on full-thickness wound in rat animal model in ۳, ۷ and ۱۴ days. Results: The particle size of Ext-AG NPs was obtained ۴۳۷±۱۵ nm. The encapsulation efficiency of extract was about ۹۱.۶%. The in vitro release profile from NPs showed that the maximum released extract was ۳۰% during ۶ days. However, by embedding of NPs into hydrogel, the release of extract was about ۱۲% after ۶ days.  The results showed that the extract could be release from hydrogel about ۳۰% in the first ۴h followed by about ۷۰% release on the fifth day. Therefore, this formulation was used in subsequent studies. Ext-CS hydrogel ۵% exhibited lower MICs on all tested microorganisms in compared with aqueous extract alone. Finally, the results of in vivo wound healing analysis revealed that on day ۳, the extract solution and Ext-CS hydrogel were more effective in reducing inflammation than chitosan gel and positive control. The process of epithelial tissue formation on day ۱۴, in all treated groups, seemed to be better than negative control, which shows the positive effect of these compounds on faster epithelial tissue formation.Conclusion: In general, it seems that S. nigrum L. leaf extract ۵% and Ext-CS hydrogel ۵% were more effective in wound healing process than other treated groups. However, the chitosan hydrogel-extract formulation showed better antimicrobial activity. 

Chemical synthesis, Characterization, Chloroquine diphosphate, Encapsulation, Gold Nanoparticles