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 protective effect of nano-curcumin in experimental model of acute pancreatitis: The involvement of TLR4/NF-kB pathway

Objective(s): The objective of the present study is to explore whether Nanocurcumin improves pancreatic inflammation through the inhibition of the TLR4/NFkB signaling pathway in cerulein-induced acute pancreatitis. Methods: Acute pancreatitis was induced by five intraperitoneal (i.p.) injection of cerulein (50 μg/kg) with 1h intervals. Vehicle and nanocurcumin (100mg/kg/day) were given to the animals by oral gavage six days before the induction of pancreatitis. The last dose was administered 1 hour before pancreatitis induction. The serum level of amylase and lipase and the tissue level of MPO enzymes were assessed by biochemical analysis. Microscopic lesions were examined. In addition, the expression level of TLR4, NF-kB p65 and TNF-α proteins were measured by western blotting analysis. Results: Nanocurcumin reduced the microscopic lesions. In addition, the drug decreased the level of amylase, lipase and MPO enzymes. Furthermore, nanocurcumin inhibited the cerulein-induced expression of TLR4, NF-kB p65 and TNF-α proteins.   Conclusion: It is suggested that the anti-inflammatory effect of nanocurcumin on cerulein-induced acute pancreatitis may involve the inhibition of the TLR4/NFkB signaling pathway

The Impact of Single Nucleotide Polymorphisms on the Pharmacokinetics of Tacrolimus in Kidney Allograft Recipients of Northern-West, Iran

Purpose: Calcineurin inhibitors (CNIs) such as tacrolimus are a major immunosuppressive therapy after renal transplantation, which inhibit cytokine expression. The pharmacokinetics of such drugs is influenced by cytochrome P450 (CYP) enzymes, multi-drug resistance-1 (MDR-1), and C25385T pregnane X receptor (PXR). This study aimed to investigate the impact of single nucleotide polymorphisms (SNP) in these genes on the ratio of tacrolimus level per drug dosage (C/D ratio), acute graft rejection, and viral infections. Methods: Kidney transplantation recipients (n=65) under similar immunosuppressive treatment were included. Amplification refractory mutation systempolymerase chain reaction (ARMS-PCR) method was applied to amplify the loci containing the SNPs of interest. Results: Overall, 65 patients with a male/female ratio of 37/28 were included. The mean age was 38±1.75 years. The variant allele frequencies of CYP3A5*3, MDR-1 C3435T, and PXR C25385T were 95.38, 20.77, and 26.92%, respectively. No significant correlations were found between the studied SNPs and the tacrolimus C/D ratios. However, there was a significant difference in the C/D ratios at 2 and 8 weeks in homozygote CYP3A5 *3/*3 carriers (P=0.015). No significant association was found between the studied polymorphisms and viral infections and acute graft rejection (P>0.05). Conclusion: Homozygote CYP3A5 *3/*3 genotype could influence the tacrolimus metabolism rate (C/D ratio)

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