Kazi Mohsin

Chitin and chitosan from Brazilian Atlantic Coast: Isolation, characterization and antibacterial activity

Chitin and chitosan were obtained by chemical treatments of shrimp shells. Different particle sizes (50-1000 μm) of the raw material were used to study their effect on size distribution, demineralization, deproteinization and deacetylation of chitin and chitosan isolation process. The particle size in the range of 800-1000 μm was selected to isolate chitin, which was achieved by measuring nitrogen, protein, ash, and yield %. Hydrochloric acid (5%, v/v) was optimized in demineralization step to remove the minerals from the starting material. Aqueous solution of sodium hydroxide (5%, w/v) at 90 °C for (20 h) was used in deproteinization step to remove the protein. Pure chitin was consequently impregnated into high concentration of sodium hydroxide (50%) for 3.5 h at 90 °C to remove the acetyl groups in order to form high pure chitosan. The degree of deacetylation (DDA) of chitosan was controlled and evaluated by different analytical tools. The chemical structure of chitin and chitosan was confirmed by elemental analysis, ATR-FTIR, H/C NMR, XRD, SEM, UV-Vis spectroscopy, TGA, and acid-base titration. The isolated chitin and chitosan from shrimp shell showed excellent antibacterial activity against Gram (-ve) bacteria (Escherichia coli) comparing with commercial biopolymers.

Novel Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) for Oral Delivery of Cinnarizine: Design, Optimization, and In-Vitro Assessment

Due to its extreme lipophilicity, the oral delivery of cinnarizine (CN) encounters several problems such as poor aqueous solubility and pH-dependent dissolution, which result in low and erratic bioavailability. The current study aims to design self-nanoemulsifying drug delivery systems (SNEDDS) of CN that circumvent such obstacles. Equilibrium solubility of CN was determined in a range of anhydrous and diluted lipid-based formulations. Dynamic dispersion tests were carried out to investigate the efficiency of drug release and magnitude of precipitation that could occur upon aqueous dilution. Droplet sizes of selected formulations, upon (1:1,000) aqueous dilution, were presented. The optimal formulations were enrolled in subsequent dissolution studies. The results showed that increasing lipid chain length and surfactant lipophilicity raised the formulation solvent capacity, while adding co-solvents provoked a negative influence. The inclusion of mixed glycerides and/or hydrophilic surfactants improved the drug release efficiency. Generally, no significant precipitation was observed upon aqueous dilution of the formulations. Five formulations were optimal in terms of their superior self-emulsifying efficiency, drug solubility, dispersion characteristics, and lower droplet size. Furthermore, the optimal formulations showed superior dissolution profile compared to the marketed (Stugeron®) tablet. Most importantly, they could resist the intensive precipitation observed with the marketed tablet upon shifting from acidic to alkaline media. However, SNEDDS containing medium-chain mixed glycerides showed the highest drug release rate and provide great potential to enhance the oral CN delivery. Accordingly, the lipid portion seems to be the most vital component in designing CN self-nanoemulsifying systems.

Momordica charantia polysaccharides mitigate the progression of STZ induced diabetic nephropathy in rats.

Diabetic nephropathy (DN) has become a primary cause of end-stage kidney disease. Several complex dynamics converge together to accelerate the advancement of DN. The present investigation was postulated to explore the mechanism of reno-protective nature of Momordica Charantia polysaccharides (MCP) by evaluating the anti-hyperglycemic, anti-lipidemic as well as markers for oxidative stress and antioxidant proficiency in streptozotocin (STZ)-induced diabetic rats. The oral administration of MCP showed a significant normalization in the levels of kidney function test in the STZ-induced diabetic rats. The levels of blood urea nitrogen (BUN), urea protein and creatinine increased by 316.58%, 195.14% and 800.97% respectively, in STZ-induced diabetic rats when compared with normal rats. MCP treatment also illustrated a significant improvement in glutathione peroxidase, superoxide dismutase and catalase levels, with a significant decline in MDA in diabetic kidneys. Immunoblots of heme-oxygenase 1 (HO-1) and Nrf2 of MCP treated diabetic rats showed a significant up-regulation of HO-1 and Nrf2 protein. Histological and ultra-structural observations also reveal that MCP efficiently protects the kidneys from hyperglycemia-mediated oxidative damage. These findings illustrate that the reno-protective nature of MCP mitigates the progression of STZ induced DN in rats by suppression of oxidative stress and amelioration of the HO-1/Nrf2 pathway.

Sinapic acid mitigates gentamicin-induced nephrotoxicity and associated oxidative/nitrosative stress, apoptosis, and inflammation in rats

AIMS In this study, the renoprotective functions of sinapic acid (SA), a polyphenol, on gentamicin-induced nephrotoxicity and the pathway that mediates this function were examined. MAIN METHODS Kidney function markers (serum urea, uric acid, creatinine, LDH, and γ-GGT) and histopathological examinations of the kidney were used to evaluate gentamicin-induced nephrotoxicity. Oxidative stress markers (lipid peroxidation and total protein), renal nitrosative stress (nitric oxide), antioxidant enzymes (catalase and NP-SH), inflammation markers (NF-κB [p65], TNF-α, IL-6, and myeloperoxidase [MPO]), and apoptotic markers (caspase 3, Bax, and Bcl-2) were also assessed. KEY FINDINGS SA (10 and 20mg/kg) pretreatment along with gentamicin restored kidney function, upregulated antioxidant levels, and downregulated lipid peroxidation and nitric oxide levels, resulting in significant decreases in oxidative and nitrosative stress. Gentamicin promoted the upregulation of renal cytokines (TNF-α and IL-6), nuclear NF-κB (p65) expression, NF-κB-DNA binding activity, and MPO activity were significantly down regulated upon SA pretreatment. Furthermore, SA pretreatment downregulated caspase 3 and Bax protein expressions and upregulated Bcl-2 protein expression. SA pretreatment also mitigated the magnitude of histological damage and reduced neutrophil infiltration in renal tubules. SIGNIFICANCE These outcomes indicated that SA pretreatment mitigates renal impairment and structural injuries via the downregulation of oxidative/nitrosative stress, inflammation, and apoptosis in the kidney.

The Studies of Phase Equilibria and Efficiency Assessment for Self-Emulsifying Lipid-Based Formulations

The study was designed to build up a database for the evaluation of the self-emulsifying lipid formulations performance. A standard assessment method was constructed to evaluate the self-emulsifying efficiency of the formulations based on five parameters including excipients miscibility, spontaneity, dispersibility, homogeneity, and physical appearance. Equilibrium phase studies were conducted to investigate the phase changes of the anhydrous formulation in response to aqueous dilution. Droplet size studies were carried out to assess the influence of lipid and surfactant portions on the resulted droplet size upon aqueous dilution. Formulations containing mixed glycerides showed enhanced self-emulsification with both lipophilic and hydrophilic surfactants. Increasing the polarity of the lipid portion in the formulation leaded to progressive water solubilization capacity. In addition, formulations containing medium chain mixed glycerides and hydrophilic surfactants showed lower droplet size compared with their long chain and lipophilic counterparts. The inclusion of mixed glycerides in the lipid formulations enormously enhances the formulation efficiency.

Silver nanoparticles enhanced flow injection chemiluminescence determination of gatifloxacin in pharmaceutical formulation and spiked urine sample

Silver nanoparticles have been utilized for the enhanced chemiluminogenic estimation of fluoroquinolone antibiotic gatifloxacin. It has been found that the weak chemiluminescence intensity produced from the reaction between calcein and KMnO4 can further be strengthened by the addition of silver nanoparticles in the presence of gatifloxacin. This phenomenon has been exploited to the quantitative determination of gatifloxacin. Under the optimum experimental conditions, the calibration curves are linear over the range of 8.9×10(-9)-4.0×10(-6) M, while the limits of detections were found to be 2.6×10(-9) M with correlation coefficient value (r(2)) 0.9999. The relative standard deviation calculated from six replicate measurements (1.0×10(-4) M gatifloxacin) was 1.70%. The method was applied to pharmaceutical preparations and the results obtained were in reasonable agreement with the amount labeled on the formulations. The proposed method was also used for the determination of gatifloxacin in spiked urine samples with satisfactory results. No interference effects from some common excipients used in pharmaceutical preparations have been found.

Oral bioavailability enhancement and hepatoprotective effects of thymoquinone by self-nanoemulsifying drug delivery system

Thymoquinone (TQ) is a poorly water soluble bioactive compound which shows poor oral bioavailability upon oral administration. Due to poor aqueous solubility and bioavailability of TQ, various self-nanoemulsifying drug delivery systems (SNEDDS) of TQ were developed and evaluated for enhancement of its hepatoprotective effects and oral bioavailability. Hepatoprotective and pharmacokinetic studies of TQ suspension and TQ-SNEDDS were carried out in rat models. Different SNEDDS formulations of TQ were developed and thermodynamically stable TQ-SNEDDS were characterized for physicochemical parameters and evaluated for drug release studies via dialysis membrane. Optimized SNEDDS formulation of TQ was selected for further evaluation of in vivo evaluation. In vivo hepatoprotective investigations showed significant hepatoprotective effects for optimized TQ-SNEDDS in comparison with TQ suspension. The oral administration of optimized SNEDDS showed significant improvement in in vivo absorption of TQ in comparison with TQ suspension. The relatively bioavailability of TQ was enhanced 3.87-fold by optimized SNEDDS in comparison with TQ suspension. The results of this research work indicated the potential of SNEDDS in enhancing relative bioavailability and therapeutic effects of natural bioactive compounds such as TQ.

Hepatoprotective effect of Commiphora myrrha against d-GalN/LPS-induced hepatic injury in a rat model through attenuation of pro inflammatory cytokines and related genes

Abstract Context: Commiphora myrrha (Burseraceae), a shrub resembling a small tree, has been used for several centuries for the treatment of various diseases. Objective: This study investigates the hepatoprotective activity of C. myrrha ethanol extract against d-galactosamine/lipopolysaccharide (d-GalN/LPS)-induced acute hepatic injury in an animal model. Materials and methods: Rats were pretreated with ethanolic extract C. myrrha (250 and 500 mg/kg; p.o.) for 7 d prior to the induction of an acute phase response by d-GalN/LPS. Animals were sacrificed 24 h after d-GalN/LPS (800 mg/kg and 50 µg/kg i.p.) administration for the biochemical and histological analyses. Results: The administration of d-GalN/LPS increased plasma aminotransferases (174.47 ± 4.5761 and 260.96 ± 1.9839 µkat/l) and total bilirubin levels (1.012 ± 0.0288 mg/dl), which were attenuated by C. myrrha treatment. Hepatic lipid peroxidation activity and nitric oxide content also increased, while the antioxidant activity measured by GSH (0.76 nmol/g protein), SOD (81.91 U/mg protein), and CAT (15.78 U/mg protein) was reduced. Commiphora myrrha provided significant restoration of GSH (0.815 nmol/gm protein), SOD (140.57 U/mg protein), and CAT (27.02 U/mg protein) levels. Furthermore, the acute phase response elicited by d-GalN/LPS administration enhanced mRNA expressions of TNF-α, IL-6, IL-10, iNOS-2, and HO-1, which were ameliorated by C. myrrha treatment. Discussion and conclusion: These findings indicate that C. myrrha considerably reduces the oxidative stress of d-GalN/LPS-induced hepatic injury via multiple pathways including adown regulation of inflammatory mediators and cytokines. Such a property might be sufficient to combat cellular damage caused by various conditions that resemble fulminant hepatitis and could be of a potential clinical application.

The fate of paclitaxel during in vitro dispersion testing of different lipid-based formulations

The purpose of the study is to investigate the effect of drug loading on representative types of lipid formulations and how drug kinetically precipitates from lipid-based systems following dispersion in aqueous media. A lipophilic model drug, paclitaxel, was formulated in representative Type II, III and IV lipid delivery systems (SEDDS and SMEDDS designed for oral administration) using oils, surfactants and/or cosolvents as excipients. Equilibrium solubilities of the drug were determined in mixtures equivalent to diluted formulations to examine the possibility of precipitation on dispersion. Precipitation kinetics were measured over time after 1:100 dilutions of formulations in aqueous media. Paclitaxel was highly soluble in Type III & IV systems (containing a high quantity of hydrophilic materials) in comparison to Type II systems. More lipophilic Type II systems typically maintained drugs in solution for several hours after dispersion. Formulations with a higher content of hydrophilic materials (Type III or Type IV) resulted in more rapid precipitation. In particular, the study suggests that Type III or Type IV formulations may be unsuitable due to their poor solubilizing properties upon dispersion even though they show high solvency in the pure form.

Simultaneous separation of antihyperlipidemic drugs by green ultrahigh-performance liquid chromatography–diode array detector method: Improving the health of liquid chromatography

Statins in combination with fibrates show beneficial effects on the lipoprotein profile of patients because they have positive complimentary effects on lipid profile. A new green ultrahigh-performance liquid chromatography-diode array detector method for simultaneous analysis of simvastatin (SMV) and fenofibrate (FNF) in standard form, marketed formulations, and self-emulsifying drug delivery system formulations was developed and validated in the present investigation. The method utilized C18 as stationary phase and a combination of methanol:water (8:2) as an eluent. It was found that selected eluent provided short run time (2.5 minutes), better peak symmetry and satisfactory values of other chromatographic parameters such as resolution (Rs=2.325), capacity factor (k, 3.0 and 4.2 for SMV and FNF, respectively), selectivity (α =1.4), and number of theoretical plates (N, 4265 and 5285 for SMV and FNF, respectively). An excellent linear relationship (r2 0.998 and 0.997 for SMV and FNF, respectively) was observed for linear regression data for the calibration plots. The developed system was validated for accuracy, precision, robustness (˃ 2% for both drugs) and recovery (98-102% for both drugs). Results obtained from the statistical treatment of the values obtained for different parameters proved that the method is suitable, reproducible, and selective for the simultaneous analysis of SMV and FNF in bulk, marketed, and self-emulsifying drug delivery system formulations. The replacement of commonly applied toxic solvents with innocuous and environmentally benign solvents provides a better option than the more toxic processes in drug analysis.