Preparation and characterization of PVA/chitosan nanofibers loaded with Dragon's blood or poly helixan as wound dressings.

Nanofibers have been investigated in regenerative medicine. Dragon's blood (DB)- and poly helixan PF (PHPF) are natural materials used in cosmetics. Herein, we generated DB- and PHPF-loaded polyvinyl alcohol/chitosan (PVA/CS/DB and PVA/CS/PHPF, respectively) nanofibers. PVA/CS/DB and PVA/CS/PHPF nanofibers had an average diameter of 547.5 ± 17.13 and 521 ± 24.67 nm, respectively as assessed by SEM, and a degradation rate of 43.1 and 47.6 % after 14 days, respectively. PVA/CS/DB and PVA/CS/PHPF nanofibers had a hemolysis rate of 0.10 and 0.39 %, respectively, and a water vapor transmission rate of ∼2200 g.m-2.day-1. These nanofibers exhibited favorable antimicrobial activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis in vitro. PVA/CS/DB and PVA/CS/PHPF nanofibers demonstrated a sustained release of 77.91 and 76.55 % over 72 h. PVA/CS/DB and PVA/CS/PHPF nanofibers had a high rate of cytocompatibility and significantly improved the viability of NIH/3T3 cells as compared with free drugs or unloaded nanofibers. Histological inspection via H&E and Verhoeff's staining demonstrated PVA/CS/DB and PVA/CS/PHPF nanofibers enhanced the wound healing and damaged tissue recovery of unsplinted wound models by promoting epithelial layer formation, collagen deposition, and enhancing the presence of fibroblasts. Conclusively, PVA/CS/DB and PVA/CS/PHPF can be introduced as potential wound dressing candidates with favorable properties.

Preparation, Characterization, and Anticancer Activity Assessment of Chitosan/TPP Nanoparticles Loaded with Echis carinatus Venom.

AIMS AND BACKGROUND: Echis carinatus venom is a toxic substance naturally produced by special glands in this snake species. Alongside various toxic properties, this venom has been used for its therapeutic effects, which are applicable in treating various cancers (liver, breast, etc.). OBJECTIVE: Nanotechnology-based drug delivery systems are suitable for protecting Echis carinatus venom against destruction and unwanted absorption. They can manage its controlled transfer and absorption, significantly reducing side effects. METHODS: In the present study, chitosan nanoparticles were prepared using the ionotropic gelation method with emulsion cross-linking. The venom's encapsulation efficiency, loading capacity, and release rate were calculated at certain time points. Moreover, the nanoparticles' optimal formulation and cytotoxic effects were determined using the MTT assay. RESULTS: The optimized nanoparticle formulation increases cell death induction in various cancerous cell lines. Moreover, chitosan nanoparticles loaded with Echis carinatus venom had a significant rate of cytotoxicity against cancer cells. CONCLUSION: It is proposed that this formulation may act as a suitable candidate for more extensive assessments of cancer treatment using nanotechnology-based drug delivery systems.

Synthesis, characterization and hepatoprotective effect of silymarin phytosome nanoparticles on ethanol-induced hepatotoxicity in rats.

Introduction: Silymarin proved to be a beneficial herbal medicine against many hepatic disorders such as alcoholic liver disease (ALD). However, its application is restricted due to its low bioavailability and consequently decreased efficacy. We herein used a nano-based approach known as "phytosome", to improve silymarin bioavailability and increase its efficacy. Methods: Phytosome nanoparticles (NPs) were synthesized using thin film hydration method. NPs size, electrical charge, morphology, stability, molecular interaction, entrapment efficiency (EE %) and loading capacity (LC %) were determined. Moreover, in vitro toxicity of NPs was investigated on mesenchymal stem cells (MSCs) viability using MTT assay. In vivo experiments were performed using 24 adult rats that were divided into four groups including control, ethanol (EtOH) treatment, silymarin/EtOH treatment and silymarin phytosome/EtOH, with 6 mice in each group. Experimental groups were given 40% EtOH, silymarin (50 mg/kg) and silymarin phytosome (200 mg/kg) through the gastric gavage once a day for 3 weeks. Biochemical parameters, containing ALP, ALT, AST, GGT, GPx and MDA were measured before and after experiment to investigate the protective effect of silymarin and its phytosomal form. And histopathological examination was done to evaluate pathological changes. Results: Silymarin phytosome NPs with the mean size of 100 nm were produced and were well tolerated in cell culture. These NPs showed a considerable protective effect against ALD through inverting the biochemical parameters (ALP, ALT, AST, GGT, GPx) and histopathological alterations. Conclusion: Silymarin phytosomal NPs can be used as an efficient treatment for ALD.

pH-sensitive HPMCP-chitosan nanoparticles containing 5-aminosalicylic acid and berberine for oral colon delivery in a rat model of ulcerative colitis.

Ulcerative colitis (UC) with continuous and extensive inflammation is limited to the colon mucosa and can lead to abdominal pain, diarrhea, and rectal bleeding. Conventional therapies are associated with several limitations, such as systemic side effects, drug degradation, inactivation, and limited drug uptake, leading to poor bioavailability. These restrictions necessitate drug delivery to the colon so that the drug passes through the stomach unchanged and has selective access to the colon. The present study aimed to formulate 5-aminosalicylic acid (5-ASA) and berberine (BBR) in chitosan nanoparticles cross-linked by HPMCP (hydroxypropyl methylcellulose phthalate) as a colon drug delivery system for UC. Spherical nanoparticles were prepared. They showed appropriate drug release in the simulated intestinal fluid (SIF), while the release did not occur in the simulated gastric fluid (SGF). They improved disease activity parameters (DAI) and ulcer index, increased the length of the colon, and decreased the wet weight of the colon. Furthermore, histopathological colon studies showed an improved therapeutic effect of 5-ASA/HPMCP/CSNPs and BBR/HPMCP/CSNPs. In conclusion, although 5-ASA/HPMCP/CSNPs showed the best effect in the treatment of UC, BBR/HPMCP/CSNPs, and 5-ASA/BBR/HPMCP/CSNPs were also effective in vivo study, and this study anticipated they could be helpful in future clinical applications for the management of UC.

Down-Regulation of CXCR4 in Mesenchymal Stem Cells by Septic Serum.

Background: Sepsis is one of the main concerns of health and one of the leading causes of death in hospitals. It is essential to manage sepsis in hospitalized patients. In recent years, cell therapy has been considered as a new approach to treat sepsis. This study evaluated the effect of CXCR4 as one of the main proteins involved in the homing of mesenchymal stem cells in the sepsis serum in mice model. Methods: Mouse sepsis model was induced by injection of E.coli and biochemical analyses was done to confirm the organ failure. Mesenchymal stem cells (MSCs) derived from bone marrow were separated into sepsis and control groups. In the sepsis serum group, MSCs were treated with sepsis serum at two time points: 24 and 48 h. Quantitative RT-PCR and flow cytometry were performed to determine the mRNA expression of CXCR4 in sepsis serum group compared to control group. Also, a migration assay was done to assess the migration capacity of bone marrow MSCs during inflammation and treatment in sepsis. Results: Our result showed that treatment with sepsis serum can control migration by decrease in CXCR4 level (P ≤ 0.05) compared to control group. Moreover it was also reported that sepsis serum decreased mRNA expression of CXCR4 in MScs. Conclusions: In our study, MSCs treated with septic serum were no longer able to migrate . Probably many variables such as source, dose, injection time, and injection route of MSCs after sepsis induction in the animal models are key factors for successful cell therapy.