Shefaat Ullah Shah

Nigella sativa provides protection against metabolic syndrome

The seeds of Nigella sativa have been used in folk medicine all over the world. The plant has been of interest due to its low degree of toxicity and beneficial pharmacological properties like antihypertensive, hypoglycemic, antifungal, anti-inflammatory, antihistaminic, antioxidant, along with significant anti-neuplastic activities. The present clinical study was undertaken to ascertain the adjuvant effect of Nigella seeds on various clinical and biochemical parameters of metabolic syndrome. After final diagnosis and considering inclusion and exclusion criteria, one hundred and fifty nine patients were enrolled in this study. Patients were divided into two groups. In Group I (standard group), patients were advised to take simvastatin 10 mg once a day, metformin 500 mg twice a day, Enalapril 10 mg once a day, Atenolol 50 mg once a day and clopidagrel 75 mg once a day for a period of six weeks. In Group II ( Nigella seeds group), patients were advised the above standard medication plus Nigella seeds 250 mg twice daily for a period of six weeks. Blood sugar both fasting and postprandial, fasting lipid profile and different parameters of obesity were recorded before therapy and after completion of therapy. It was found that the addition of Nigella seeds provide beneficial effects in all the clinical and biochemical parameters for the adult’s treatment panel-III of metabolic disorders especially in fasting blood sugar, low density lipoproteins and high density lipoproteins. No sign of toxicity of the plant appeared in the Group II. Improvement in all other parameters like blood pressure, circumference of waist and serum triglyceride was also observed. Thus, Nigella seeds were found to be effective as an adjuvant therapy in patients of dyslipidemia and hyperglycemia. Keywords: Nigella sativa , toxicity, hyperglycemia, adjuvant, antihistaminic, antioxidant, patients

Synthesis and characterization of S-nitrosoglutathione-oligosaccharide-chitosan as a nitric oxide donor

Objectives: The aim of this work is to synthesize a novel stable and biodegradable nitric oxide (NO) donor polymer based on a chitosan backbone. This polymer needed to be linked to glutathione (GSH), which was nitrosated in a second step. This polymer has been developed as an NO delivery platform that could be further evaluated for an oral delivery in Crohn’s disease. Methods: The new polymer (named S-nitrosoglutathione-oligosaccharide-chitosan or SNOC) was obtained using a two-step procedure involving the linkage of GSH to chitosan via an amidine reaction followed by a post-nitrosation with NaNO2. The GSH linkage was assessed using NMR, FTIR and an Ellman’s test, whereas the final NO amount was determined by the Griess and Saville method. Results: Polymers with different numbers of NO groups were obtained (159.04 ± 64.16 µmol/g of polymer for SNOC G1 and 525.08 ± 151.35 µmol/g of polymer for SNOC G2) depending on the procedure used for production. When tested in an Ussing chamber, SNOC G2 had a sustained release of NO and nitrites for at least 6 h. Conclusion: We believe that this type of polymer is adapted for the development of various formulations, including microparticles.

Release pattern of three new polymers in Ketoprofen controlled-release tablets

The objective of the study was to formulate and evaluate sustained release polymeric tablets of ketoprofen for the release rate, release patterns and the mechanism involved in the release process of the drug. Formulations with three different types of newly synthesized polymers and one grade of ethyl cellulose ether derivatives (FP100 premium) in several drug-to-polymer ratios (D:P ratio 10:1, 10:2 and 10:3) were compressed into tablets using the direct compression method. They were examined for their physical properties and appearance. Tablets dimensional tests (thickness, diameter) and Q.C tests (hardness, friability, disintegration) were performed according to the USP methods. For in vitro drug release studies of Ketoprofen controlled release (CR) tablets, the USP Method-1 (Rotating Basket Method) was used with Pharma test dissolution apparatus (D-63512 Hainburg, Germany). The medium used for dissolution was phosphate buffer having a pH of 7.4 kept at constant temperature of 37±1°C. In order to analyze the drug release kinetics from each of the prepared matrices, five different mathematical models were applied to the release data including zero order kinetics, first order kinetics, Higuchi kinetics, Hixson Crowell kinetics and Korsmeyer Peppas equations were applied to the release data. The results obtained from different parameters showed that polymers: Polyglycolide, PGA-cocaprolactone, PGA-co-pentadecalactone and Ethocel FP100 premium can be used successfully in order to develop directly compressed prolonged release tablets of slightly soluble drugs such as ketoprofen. Particle size of polymer is a determining factor in controlling the release of ketoprofen from tablets. Ethocel standard FP100 polymers extend the release rates of drug more efficiently than the conventional granular form of the other three polymers. Further, the three new polymers and Ethocel FP100 could efficiently extend the release of the drugs as compared to the reference conventional formulation.

From nanoemulsions to self-nanoemulsions, with recent advances in self-nanoemulsifying drug delivery systems (SNEDDS)

ABSTRACT Introduction: Lipid-based drug delivery systems (LBDDS) are the most promising technique to formulate the poorly water soluble drugs. Nanotechnology strongly influences the therapeutic performance of hydrophobic drugs and has become an essential approach in drug delivery research. Self-nanoemulsifying drug delivery systems (SNEDDS) are a vital strategy that combines benefits of LBDDS and nanotechnology. SNEDDS are now preferred to improve the formulation of drugs with poor aqueous solubility. Areas covered: The review in its first part shortly describes the LBDDS, nanoemulsions and clarifies the ambiguity between nanoemulsions and microemulsions. In the second part, the review discusses SNEDDS and elaborates on the current developments and modifications in this area without discussing their associated preparation techniques and excipient properties. Expert opinion: SNEDDS have exhibit the potential to increase the bioavailability of poorly water soluble drugs. The stability of SNEDDS is further increased by solidification. Controlled release and supersaturation can be achieved, and are associated with increased patient compliance and improved drug loads, respectively. Presence of biodegradable ingredients and ease of large-scale manufacturing combined with a lot of ‘drug-targeting opportunities’ give SNEDDS a clear distinction and prominence over other solubility enhancement techniques.

Synthesis of S-nitrosoglutathione-alginate for prolonged delivery of nitric oxide in intestines

Abstract S-nitrosothiols are a class of NO-donors currently under investigation for the treatment of various diseases. In this study, we developed a novel NO-donor (S-nitrosoglutathione-alginate, SNA) by cross-linking alginate with S-nitrosothiols, which can deliver NO in a sustained manner. This compound can be further evaluated for oral delivery to treat Crohn’s disease. This new compound was prepared using a two-step procedure involving (I) linkage of reduced glutathione to alginate and (II) post-nitrosation with sodium nitrite (NaNO2). The amount of linked thiol moieties for the possible nitrosation was calculated using Ellman’s method, and the amount of NO abducted on the polymer was calculated using the Griess–Saville method. An ex vivo model (i.e. Ussing chamber) was used to investigate the permeation of this new NO-donor across the rat intestinal barrier. We obtained polymers with different numbers of abducted NOs (174 ± 21 μmol/g for SNA F1 and 468 ± 23 μmol/g for SNA F2) depending on the procedure used for nitrosation. In the ex vivo studies in the Ussing chamber, SNA F2 exhibited a sustained release for at least 10 h. The effect of pH on the stability of the new compound was also investigated, and the new compound was more stable at a mildly basic pH of 8.4 where 73% remained after 1 week. However, only 50% remained after 1 week at an acidic pH of 1.2. In the cytotoxicity studies (Caco2), this compound was nontoxic at concentrations of less than 200 μM.

Mechanisms Underlying Anti-hyperalgesic Properties of Kaempferol-3,7- di-O-α-L-rhamnopyranoside Isolated from Dryopteris cycadina

BACKGROUND The present study was designed to evaluate the anti-hyperalgesic effect of kaempferol-3,7-di-O-α-L-rhamnopyranoside isolated from the ethyl acetate soluble part of Dryopteris cycadina. Pretreatment of the compound at the doses of 2.5, 5, and 10 mg/kg caused a significant reduction in abdominal constrictions in acetic acid-induced writhing test with maximum effect of 63.03% (P < 0.001) at 10 mg/kg i.p. When subjected in formalin test, it evoked a marked antinociceptive effect in both phases in a dose-dependent manner. The maximum (p < 0.01) pain-inhibiting effects were 61.36% and 65.89% in 1st and 2nd phases at 10 mg/kg i.p., respectively. Administration of atropine (non-selective cholinergic receptor antagonist) significantly (p < 0.05) antagonized the antihyperalgesic effect of the compound, while glibenclamide and naloxone did not alter the induced antinociceptive effect and thus, antinociceptive activity of the compound is mediated, at least in part, through cholinergic system antagonism; independent of calcium channel and opioidergic receptor participation. Furthermore, docking studies underlined strong COX-2 inhibitory activity of the compound. RESULT Our data concluded that overall analgesic activity of the compound seems to involve COX-2 inhibition and activation of cholinergic receptors. However, further detailed studies are required in this direction to confirm the analgesic effect of the compound for its possible clinical utility.

Thiomers and their potential applications in drug delivery

ABSTRACT Introduction: Thiomers are the product of the immobilization of sulfhydryl-bearing ligands onto the polymer backbone of a conventional polymer, which results in a significant improvement in mucoadhesion; in situ gelation and efflux inhibition compare with unchanged polymers. Because of thiol groups, thiomers have more reactivity and enhanced protection against oxidation. Since the late 1990s, extensive work has been conducted on these promising polymeric excipients in the pharmaceutical field. Areas covered: This review covers thiomers, their classification and their different properties. Various techniques for the synthesis, purification and characterization of thiomers are described in detail. This review also encompasses their various properties such as mucoadhesion, permeation enhancement, in situ gelation and efflux inhibition, as well as different formulations based on thiomers. In addition to the use of thiomers as multifunctional excipients, this review also encompasses their use as drugs. Expert opinion: The synthesis is realized by linkage of sulfhydryl-bearing ligands but reported methods give low yields. Higher degrees of modification are not necessary and would probably lead to extreme changes in properties. Nevertheless, an accurate characterization of the final product is important. The scale-up procedure for industrial manufacturing has been adapted to produce GMP materials; Lacrimera® eye drops have already entered the European market.

Proniosomes derived niosomes: recent advancements in drug delivery and targeting

Abstract Vesicular drug delivery systems have gained wide attention in the field of nanotechnology. Among them proniosomes become the superior over other vesicular carriers. Proniosomes are dry formulations of water soluble nonionic surfactant coated carrier system which immediately forms niosomes upon hydration. They have the capability to overcome the instability problems associated with niosomes and liposomes and have the potential to improve solubility, bioavailability, and absorption of various drugs. Furthermore, they offer versatile drug delivery concept for enormous number of hydrophilic and hydrophobic drugs. They have the potential to deliver drugs effectively through different routes at specific site of action to achieve controlled release action and reduce toxic effects associated with drugs. This review discusses the general preparation techniques of proniosomes and mainly focus on the applications of proniosomes in drug delivery and targeting. Moreover, this review demonstrates critical appraisal of the literature for proniosomes. Additionally, this review extensively explains the potential of proniosomes in delivering drugs via different routes, such as oral, parenteral, dermal and transdermal, ocular, oral mucosal, vaginal, pulmonary, and intranasal. Finally, the comparison of proniosomes with niosomes manifests the clear distinction between them. Moreover, proniosomes need to be explored for proteins and peptide delivery and in the field of nutraceuticals and develop pilot plant scale up studies to investigate them in industrial set up.

STUDY OF THE CHEMICAL AND METABOLIC CHANGES IN PLASMA GLUTATHIONE (GSH) OF HUMAN BLOOD AFTER LITHIUM INTRODUCTION

Lithium remains a mainstay in the acute and prophylactic treatment of bipolar affective disorder. It is used in the augmentation of antidepressant treatment and, less frequently, in the augmentation of antipsychotic treatment of schizophrenia. It is reported to have specific anti-suicidal effects. Systematic reviews by the Cochrane collaboration and others have examined the evidence base or its use in these contexts. Thus it is interesting to study the effect of Lithium on the Glutathione. The effect of Lithium on the chemical status of the glutathione in plasma has been studied using Ellman’s method. The effect of Lithium on the chemical status of glutathione was determined in plasma for concentration and time dependent effects. There was found a drastic effect on decreasing the concentration of glutathione in plasma as the concentration is increased and time has passed. The decrease in the Glutathione level was concentration and time of interaction dependent, probably due to oxidation of GSH to corresponding disulphide (GSSG).In this paper the effect of Lithium metal on thiol /GSH level was discussed in vitro, which in principal may present a model of in vivo reaction.