The effect of berberine nanomicells on hepatic cirrhosis in bile duct ligated rats

The present study was designed to investigate the possible hepatoprotective effect of berberine (BBR) nano micelles on liver cirrhosis induced by bile duct ligation model (BDL) in male rats. Introduction: The anti-fibrotic effect of chronic berberine (BBR) had previously demonstrated in a rat model of bile duct ligation (BDL) - induced liver fibrosis. As a result, the aim of present study was to investigate the possible hepatoprotective effect of BBR nanomicelles on liver cirrhosis induced by Bile duct ligation model (BDL) in male rats. Methods and Results: Male Wistar rats were divided into 7 groups (n= 6) including sham-operated, BDL + saline, BDL + nanoBBR (50 mg/kg, p.o.), BDL + nanomicelles, BDL + BBR (50 and 100 mg/kg, p.o.), BDL + silymarin (100 mg/kg, p.o.). After 21 days of drugs' treatments following bile duct ligateation, the serum and tissue levels of some hepatic markers were measured and pathologic evaluations performed.BDL could markedly increase aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBIL) serum levels and tissue tumor necrosis factor-alpha (TNF-α), level along with reductions in tissue levels of glutathione (GSH), superoxide dismutase (SOD) and total protein levels. On the other hand, BBR nanomicelles (50 mg/kg, p.o.) and silymarin (100 mg/kg, p.o.) markedly decreased the serum levels of AST and ALT while enhanced GSH level. In addition, BBR nanomicelles (50 mg/kg, p.o.), silymarin (100 mg/kg, p.o.) and BBR (100 mg/kg, p.o.) groups showed a considerable increase in SOD levels. BBR nanomicelles (50 mg/kg, p.o.) significantly lowered TNF-α level. In addition, nanoBBR group prevented liver cirrhosis in histopathologic analysis.  Conclusions:Therefore, formulation of BBR nanomicelles may represent a good approach to enhance the effect of BBR in liver injuries

The effect of berberine nanomicelles on hepatic cirrhosis in bile duct-ligated rats

Objective (s): The anti-fibrotic effect of chronic berberine (BBR) had demonstrated previously in a rat model of bile duct ligation (BDL). The aim of present study was to investigate hepatoprotective effect of BBR nanomicelles on liver cirrhosis induced by BDL in male rats.Materials and methods: After 21 days of drugs’ treatments, the serum and tissue levels of hepatic markers were measured and pathologic evaluations performed.Results: BDL could markedly increase aspartate aminotransferase (AST), alanine aminotransferase (ALT), LDH, and total bilirubin (TBIL) serum levels and tissue tumor necrosis factor-alpha (TNF-α) level along with reductions in tissue levels of key antioxidants glutathione (GSH) and superoxide dismutase (SOD) as well as total protein. On the other hand, silymarin (100 mg/kg, p.o.), BBR (100 mg/kg) and BBR nanomicelles (50 mg/kg, p.o.) markedly decreased AST and ALT while enhanced GSH. In addition, BBR nanomicelles (50 mg/kg, p.o.), silymarin (100 mg/kg, p.o.) and BBR (100 mg/kg, p.o.) groups showed a considerable increase in SOD. BBR nanomicelles (50 mg/kg, po.) significantly lowered TNF-α. In addition, nanoBBR treatment prevented liver cirrhosis in histopathologic analysis.Conclusion: Formulation of BBR may represent a worthy approach to enhance the effect of it in liver injuries

Benefit of magnesium-25 carrying porphyrin-fullerene nanoparticles in experimental diabetic neuropathy

Diabetic neuropathy (DN) is a debilitating disorder occurring in most diabetic patients without a viable treatment yet. The present work examined the protective effect of 25Mg-PMC16 nanoparticle (porphyrin adducts of cyclohexil fullerene-C60) in a rat model of streptozotocin (STZ)-induced DN. 25Mg-PMC16 (0.5 lethal dose50 [LD50]) was administered intravenously in two consecutive days before intraperitoneal injection of STZ (45 mg/kg). 24Mg-PMC16 and MgCl2 were used as controls. Blood 2,3-diphosphoglycerate (2,3-DPG), oxidative stress biomarkers, adenosine triphosphate (ATP) level in dorsal root ganglion (DRG) neurons were determined as biomarkers of DN. Results indicated that 2,3-DPG and ATP decreased whereas oxidative stress increased by induction of DN which all were improved in 25Mg-PMC16-treated animals. No significant changes were observed by administration of 24Mg-PMC16 or MgCl2 in DN rats. It is concluded that in DN, oxidative stress initiates injuries to DRG neurons that finally results in death of neurons whereas administration of 25Mg-PMC16 by release of Mg and increasing ATP acts protectively

A randomized clinical trial on the anti-tumoral effects of low molecular weight heparin in the treatment of esophageal cancer

The current treatment approaches for esophageal cancer are associated with poor survival, and there are ongoing efforts to find new and more effective therapeutic strategies. There are several reports on the antitumoral effects of low‐molecular‐weight heparins (LMWHs). We have assessed the possible survival benefit of LMWHs in esophageal malignancies. This was a randomized, single‐blind, multicenter, Phase II clinical trial on nonmetastatic esophageal cancer candidate for neoadjuvant chemoradiotherapy. Patients were randomly assigned to the chemoradiotherapy‐only arm or chemoradiotherapy plus enoxaparin arm using 1:1 allocation. Radiotherapy was delivered in 1.8‐Gy daily fractions to a dose of 50.4 Gy in both groups. Paclitaxel 50 mg/m2 and carboplatin (AUC 2) were administered weekly, concurrent with radiotherapy. In the intervention group, patients received enoxaparin (40 mg) and chemoradiation daily. 4–6 weeks after treatment, all patients underwent esophagectomy. After a median follow up of 7 months, estimated 1 year disease‐free survival (DFS) in the intervention group was 78.9% and was 70% in the control groups ( p = 0.5). Toxicity from the experimental treatment was minimal, and there were no treatment‐related deaths. A pathologically complete response in intervention and control group was 64.8% and 62.5%, respectively ( p = 0.9). There was a nonsignificant trend toward improved survival by the addition of enoxaparin to the concurrent chemoradiotherapy regimen. However, 1 y DFS of both groups were high as expected. A longer follow‐up and a larger sample size are required.delivered in 1.8-Gy daily fractions to a dose of 50.4 Gy in both groups. Paclitaxel 50 mg/m2 and carboplatin (AUC 2) were administered weekly concurrent with radiotherapy. In the intervention group, patients received enoxaparin (40 mg) daily as well as chemoradiation. Four to six weeks after treatment, all patients underwent esophagectomy. After a median follow up of 7 months,estimated one year disease free survival (1y DFS) in the intervention group was 78.9% and in the control groups was 70% (p=0.5). Toxicity from the experimental treatment was minimal and there were no treatment-related deaths. A Pathologically complete response in intervention and control group was 64.8% and 62.5%, respectively (p=0.9). There was a non-significant trend toward improved survival by the addition of enoxaparin to the concurrent chemoradiotherapy regimen. However, 1y DFS of both groups were high as expected. A longer follow-up and larger sample size is required

Nanotechnology in Wound Healing; Semisolid Dosage Forms Containing Curcumin-Ampicillin Solid Lipid Nanoparticles, in-Vitro, Ex-Vivo and in-Vivo Characteristics

Purpose: Wound healing is a natural biologic process, but the duration of it may take too long. Trying to shorten this process is one of the challenges for scientists. Many technologies were applied to achieve this goal as well as nanotechnology. In this study semi solid formulations containing curcumin and ampicillin solid lipid nanoparticles (SLNs) were prepared to evaluate as burn wound healing agent. Methods: Curcumin as an anti-inflammatory and anti-bacterial agent and ampicillin as an antibiotic were applied. In-vitro and in-vivo evaluations were carried out. Particle size, loading efficiency, release profile, morphology and anti-bacterial efficacy of desired nanoparticles were evaluated at first. Then the remaining of the antibacterial effect in semi solid preparations was studied. Animal studies for both toxicology using rabbits and skin burn model using rats were designed. Pathology studies after applying of formulations was done too. Results: Desired nanoparticles were spherical in shape and particle size in range of 112-121 nm, with low zeta potential. For increasing stability of particles they were freeze dried using cryoprotectant. Lyophilized particles show no significant size enlargement. Results showed that both ointment and gel preparations have reasonable anti-bacterial effects, both of them cause increasing in the rate of wound healing in comparison with placebos and control groups and none of the formulations showed acute toxicity. Conclusion: It seems that using nanotechnology could shorten wound healing process to reduce treatment costs and increase compliance of patients

In Vitro Co-Delivery Evaluation of Novel Pegylated Nano-Liposomal Herbal Drugs of Silibinin and Glycyrrhizic Acid (Nano-Phytosome) to Hepatocellular Carcinoma Cells

Objective This study aimed to evaluate a co-encapsulated pegylated nano-liposome system based on two herbal anti-tumor drugs, silibinin and glycyrrhizic acid, for delivery to a hepatocellular carcinoma (HCC) cell line (HepG2). Materials and Methods In this experimental study, co-encapsulated nano-liposomes by the thin layer film hydration method with HEPES buffer and sonication at 60% amplitude. Liposomes that co-encapsulated silibinin and glycyrrhizic acid were prepared with a specified molar ratio of dipalmitoylphosphatidylcholine (DPPC), cholesterol (CHOL), and methoxy-polyethylene glycol 2000 (PEG2000)–derived distearoyl phosphatidylethanolamine (mPEG2000-DSPE). We used the MTT technique to assess cytotoxicity for various concentrations of co-encapsulated nano-liposomes, free silibinin (25% w/v) and glycyrrhizic acid (75% w/v) on HepG2 and fibroblast cell lines over a 48-hour period. Results Formulation of pegylated nano-liposomes showed a narrow size distribution with an average diameter of 46.3 nm. The encapsulation efficiency (EE) for silibinin was 24.37%, whereas for glycyrrhizic acid it was 68.78%. Results of in vitro cytotoxicity showed significantly greater co-encapsulated nano-liposomes on the HepG2 cell line compared to the fibroblast cell line. The half maximal inhibitory concentration (IC50) for co-encapsulated pegylated nanoliposomal herbal drugs was 48.68 µg/ml and free silibinin with glycyrrhizic acid was 485.45 µg/ml on the HepG2 cell line. Conclusion This in vitro study showed that nano-liposome encapsulation of silibinin with glycyrrhizic acid increased the biological activity of free drugs, increased the stability of silibinin, and synergized the therapeutic effect of silibinin with glycyrrhizic acid. The IC50 of the co-encapsulated nano-liposomes was lower than the combination of free silibinin and glycyrrhizic acid on the HepG2 cell line

Dermal toxicity of Colloidal Nanosilver in Albino Rabbit: A New Approach to Physicochemical Properties

Objective(s): Silver nanoparticles have been widely used as new potent antimicrobial agents in cosmetic and hygienic products, as well as in new medical devices. Serious concerns have been expressed on the potential health risks of dermal applications of nanosilver containing consumer products (AgNPs), therefore regulatory health risk assessment has become necessary for the safe usage of AgNPs in biomedical products with special emphasis to their dermal toxicity potentials. We aimed in the present study to compare the dermal toxicity of three different AgNP containing disinfectantsin an albino rabbit model and tried to determine the role of size and other physicochemical properties on their possible dermal toxicity. Methods: After the characterization of all three samples by transmission electron microscopy (TEM), X-Ray Diffraction (XRD) and Dynamic Light Scattering (DLS) , corrosive and irritant potentials  of AgNPs in three different sizes of three colloidal AgNPs were scored by the OECD 404 guideline with necessary modifications and were applied under the specified concentrations via nanosilver skin patches on the shaved skin of young female albino rabbits. All skin reactions were recorded in 3 min as well as in 1, 4, 24, 48 and 72 hours from the application and compared with the control group and followed up for 14 days. Results: Although short-term observations didn’t show any significant changes in the weight of animals and macroscopic  variables, long-term histopathological abnormalities were seen in the skin of all test groups, which was not associated with the size and other physicochemical properties of AgNP samples. The toxicity manifestations were dry skin, scaling in doses lower than 100 ppm and erythema in higher doses up to 4000 ppm which was reversed. Conclusions: This finding creates a new issue in the possible dermal effects of all colloidal AgNPs, containing nano health products, which should be considered in future studies by focusing on other physicochemical properties of AgNPs and possible underlying mechanisms of toxicity by conducting cellular models

ATP depletion and oxidative damage of hepatic cells following acute exposure to malathion in rat: beneficial role of porphyrin–fullerene nanoparticles carrying magnetic magnesium

The objective of the present study was to investigate the role of nanocarrier of magnetic isotope of 25-Mg2+ (PMC16) in liver toxicity, ATP content and oxidative stress due to malathion (MAL) exposure. PMC16 nanoparticles were administered in different doses (0.05, 0.1 and 0.2 LD50) intravenously (iv) 40 minutes after a single MAL (0.25 LD50= 207 mg/kg) intraperitoneal (ip) injection as a complement to standard therapy of pralidoxime (PAM) and atropine (AT). MgSO4 was used as another supplement for comparison with PMC16. ATP/ADP ratio, antioxidant enzymes including catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), and oxidative stress biomarker including lipid peroxidation (LPO) were evaluated in liver tissue cells. Results indicated that after MAL administration, ADP/ATP ratio had a significant increase in liver tissues in comparison with control but this ratio was improved using various doses of PMC16. LPO was significantly decreased at all doses of PMC16 and MgSO4 when compared with MAL-exposed group. SOD and CAT activities significantly were increased in MAL-treated group as compared to saline group. SOD was reduced by all doses of PMC16 and CAT activity was decreased in PMC16-0.1 group. These results lead us to conclude that PMC16 and MgSO4 are so useful for protection against MAL-induced liver toxicity, ATP depletion and oxidative damages

Evaluation of the effects of hyaluronic acid on poly (3-hydroxybutyrate)/chitosan/carbon nanotubes electrospun scaffold: structure and mechanical properties

In this study, a combination of poly (3-hydroxybutyrate) (PHB), chitosan (Cs), multiwall carbon nanotubes (MWNTs), and different concentrations of Hyaluronic Acid (HA) were electrospun. The results showed that the produced nanofibers are uniform. Incorporation of HA, Cs and MWNTs reduced the water contact angle and made the scaffolds more hydrophilic. The porosity of the scaffolds was in the range of 80-88%. The presence of MWNTs increased the tensile strength of scaffolds and different concentrations of HA had no much diverse effects. In conclusion, the PHB-Cs-MWNTs-HA 10% electrospun scaffold could be a good candidate for cartilage tissue engineering applications