STUDY OF ENHANCED ANTI-INFLAMMATORY POTENTIAL OF NIGELLA SATIVA IN TOPICAL NANOFORMULATION

Objective: Formulate a nanocarrier for enhancing the anti-inflammatory activity of thymoquinone (Tq), a major active constituent of Nigella sativa.Methods: Nanoformulation of Tq was developed by low energy emulsification techniques. NanoTqs were pre-screened by different thermodynamic stability tests, followed by in vitro release, zeta potential, viscosity, the transmittance (%), globule size distribution and ex vivo studies. The morphology of the optimized NanoTq was determined by transmission electron microscopy (TEM) which revealed fairly spherical shape and good correlation with particle size distribution study. The formulation used for assessment of the anti-inflammatory potential and permeability enhancement contained mixture of essential oil of Nigella sativa: Capryol 90 (3:7, 10%, v/v), Tween 80 (21.75%, v/v), PEG 400 (7.25%, v/v) and double distilled water (61%, v/v).Results: The in vitro permeation of Tq from optimized formulations was found extremely significant (p<0.001) in comparison to apiTq. The steady state flux (Jss), the permeability coefficient (Kp) and enhancement ratio (Er) of NanoTq gel was determined and compared with apiTq. The comparative anti-inflammatory effects of the optimized formulations NanoTq, apiTq and DicloGel was assessed on the edema in the carrageenan-induced paw model in Wistar rats. Therapeutic potential of NanoTq was found statistically extremely significant (P<0.0001) compared to apiTq and insignificant comparable with standard DicloGel. Storage stability of NanoTq showed insignificant changes in the zeta potential, droplet size and was free from any physical instability.Conclusion: The optimized nano formulation with a lower dose of Tq showed better anti-inflammatory effects, indicating greater absorption capability through the stratum corneum

A survey of microbiological quality of fish sold in two local wet markets

Eight marine fish species were obtained from two nearby wet markets (Sungei Besi and Kajang). The fish were analysed for total viable counts, coliforms, Vibrio parahaemolyticus and histamine-producingbacteria. Total viable count was determined using Plate Count Agar; coliforms using McConkey Broth; Vibrio parahaemolyticus by TCBS a garand histamine-producing bacteria were determined using Niven's media. The total counts on all fish from both markets ranged from 1rf to 1rf per gram offish, coliforms ranged from 1rJ to 1rf pergram, and all thefish examined were positive for both Vibrio parahaemolyticus and histamine-producing bacteria

Inhibition of the Growth of Plasmodium falciparum in Culture by Stearylamine-Phosphatidylcholine Liposomes

We have examined the effect of stearylamine (SA) in liposomes on the viability of Plasmodium falciparum in culture by studying the inhibition of incorporation of [3H]-hypoxanthine in the nucleic acid of parasites. Stearylamine in liposomes significantly inhibits the growth of the parasites depending on the phospholipids composition. The maximum inhibition was observed when SA was delivered through Soya phosphatidylcholine (SPC) liposomes. The chain length of alkyl group and density of SA in liposomes play a significant role in inhibiting the growth of the parasites. Incorporation of either cholesterol or Distearylphosphatidylethanolamine−Methoxy-Polyethylene glycol-2000 (DSPE-mPEG-2000) in Soya phosphatidylcholine-stearylamine (SPC-SA) liposomes improves the efficacy. Intraerythrocytic entry of intact SPC-SA liposomes into infected erythrocytes was visualized using fluorescent microscopy. No hemolysis was observed in uninfected erythrocytes, and slight hemolysis was noted in infected erythrocytes at high concentrations of SPC-SA liposomes. Overall, our data suggested SA in SPC-liposomes might have potential application in malaria chemotherapy

Mechanistic approach for the development of ultrafine oil-water emulsions using monoglyceride and blends of medium and long chain triglycerides: enhancement of the solubility and bioavailability of Perphenazine

A kinetically stable ultra-fine oil-water (o/w) emulsion containing Perphenazine and blends of long and medium chain triglycerides was prepared. The purpose of the ultra-fine emulsion was to increase the oral bioavailability of Perphenazine. The formulations were prepared using a low energy emulsification phase titration method. The optimized formulations consisted of blends of linseed oil and Sefsol 218 (1:1) (oil phase), polysorbate 40 (surfactant), polyethylene glycol 400 (cosurfactant) and distilled water (dispersion medium). Characterization of viscosity, refractive index, particle size distribution, spectral transmittance and surface morphology of the formulations was performed. The release rate of Perphenazine from the formulations was quantified using the everted gut sac of rat intestinal mucosa. The ex vivo release data demonstrated that the formulated nanoemulsions increased significantly the permeation rate of Perphenazine when compared with a suspension. Following oral administration of selected nanoemulsions in Wistar rats, the AUC and Cmax of Perphenazine increased by 2.9 and 2.54-fold respectively compared with the Perphenazine suspension. The observed increase in bioavailability may be due to the increase in the dissolution rate from the molecularly dissolved drug in the oil phase and an increased rate of dispersion of the drug in the gastrointestinal (GI) tract which leads to greater absorption into the blood

Identification of Phytoconstituents as Potent Inhibitors of Casein Kinase-1 Alpha Using Virtual Screening and Molecular Dynamics Simulations

Casein kinase-1 alpha (CK1α) is a multifunctional protein kinase that belongs to the serine/threonine kinases of the CK1α family. It is involved in various signaling pathways associated with chromosome segregation, cell metabolism, cell cycle progression, apoptosis, autophagy, etc. It has been known to involve in the progression of many diseases, including cancer, neurodegeneration, obesity, and behavioral disorders. The elevated expression of CK1α in diseased conditions facilitates its selective targeting for therapeutic management. Here, we have performed virtual screening of phytoconstituents from the IMPPAT database seeking potential inhibitors of CK1α. First, a cluster of compounds was retrieved based on physicochemical parameters following Lipinski’s rules and PAINS filter. Further, high-affinity hits against CK1α were obtained based on their binding affinity score. Furthermore, the ADMET, PAINS, and PASS evaluation was carried out to select more potent hits. Finally, following the interaction analysis, we elucidated three phytoconstituents, Semiglabrinol, Curcusone_A, and Liriodenine, posturing considerable affinity and specificity towards the CK1α binding pocket. The result was further evaluated by molecular dynamics (MD) simulations, dynamical cross-correlation matrix (DCCM), and principal components analysis (PCA), which revealed that binding of the selected compounds, especially Semiglabrinol, stabilizes CK1α and leads to fewer conformational fluctuations. The MM-PBSA analysis suggested an appreciable binding affinity of all three compounds toward CK1α

Alu-repeat–induced deletions within the NCF2 gene causing p67- phox –deficient chronic granulomatous disease (CGD)

Mutations that impair expression or function of the components of the phagocyte NADPH oxidase complex cause chronic granulomatous disease (CGD), which is associated with life-threatening infections and dysregulated granulomatous inflammation. In five CGD patients from four consanguineous families of two different ethnic backgrounds, we found similar genomic homozygous deletions of 1,380 bp comprising exon 5 of NCF2 , which could be traced to Alu-mediated recombination events. cDNA sequencing showed in-frame deletions of phase zero exon 5, which encodes one of the tandem repeat motifs in the tetratricopeptide (TPR4) domain of p67- phox . The resulting shortened protein (p67Δ5) had a 10-fold reduced intracellular half-life and was unable to form a functional NADPH oxidase complex. No dominant negative inhibition of oxidase activity by p67Δ5 was observed. We conclude that Alu-induced deletion of the TPR4 domain of p67- phox leads to loss of function and accelerated degradation of the protein, and thus represents a new mechanism causing p67- phox –deficient CGD. Hum Mutat 30:1–8, 2009. © 2009 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64904/1/21156_ftp.pd

Mechanistic approach for the development of ultrafine oil-water emulsions using monoglyceride and blends of medium and long chain triglycerides: enhancement of the solubility and bioavailability of Perphenazine

A kinetically stable ultra-fine oil-water (o/w) emulsion containing Perphenazine and blends of long and medium chain triglycerides was prepared. The purpose of the ultra-fine emulsion was to increase the oral bioavailability of Perphenazine. The formulations were prepared using a low energy emulsification phase titration method. The optimized formulations consisted of blends of linseed oil and Sefsol 218 (1:1) (oil phase), polysorbate 40 (surfactant), polyethylene glycol 400 (cosurfactant) and distilled water (dispersion medium). Characterization of viscosity, refractive index, particle size distribution, spectral transmittance and surface morphology of the formulations was performed. The release rate of Perphenazine from the formulations was quantified using the everted gut sac of rat intestinal mucosa. The ex vivo release data demonstrated that the formulated nanoemulsions increased significantly the permeation rate of Perphenazine when compared with a suspension. Following oral administration of selected nanoemulsions in Wistar rats, the AUC and Cmax of Perphenazine increased by 2.9 and 2.54-fold respectively compared with the Perphenazine suspension. The observed increase in bioavailability may be due to the increase in the dissolution rate from the molecularly dissolved drug in the oil phase and an increased rate of dispersion of the drug in the gastrointestinal (GI) tract which leads to greater absorption into the blood