Paras Nath Singh

Polymeric nanoparticulate system: a potential approach for ocular drug delivery.

Various efforts in ocular drug delivery have been made to improve the bioavailability and to prolong the residence time of drugs applied topically onto the eye. The potential use of polymeric nanoparticles as drug carriers has led to the development of many different colloidal delivery vehicles. Drug loaded polymeric nanoparticles (DNPs) offer several favorable biological properties, such as biodegradability, nontoxicity, biocompatibility and mucoadhesiveness. These submicron particles are better than conventional ophthalmic dosage forms to enhance bioavailability without blurring the vision. DNPs have been shown to be amenable to targeting of the drug to the site of action, leading to a decrease in the dose required and a decrease in side effects. Additionally, DNPs can be fabricated by simple techniques with better physical stability than liposomes. This unique combination of properties makes DNPs a novel polymeric drug delivery device, which fulfils the requirements for ophthalmic application. This review discusses the polymeric nanoparticles, physiochemical characterization, fabrication techniques, therapeutic significances, patented technology of nanoparticles and future possibility in the field of ocular drug delivery.

Toxicological screening of traditional medicine Laghupatha (Cissampelos pareira) in experimental animals.

Laghupatha (Cissampelos pareira) a important medicinal plant in Indian traditional system of medicine and is widely used in many countries by different tribal. Despite the wide use of Cissampelos pareira in folk medicine, no study has been published in the scientific literature about its toxicological profile. In present study 50% aqueous ethanolic extract of Cissampelos pareira (Menispermaceae) was evaluated for the acute and subacute toxicity. In the acute toxicity test, oral administration of 2g/kg of Cissampelos pareira produced neither mortality nor changes in behavior or any other physiological activities in mice. In subacute toxicity studies, no mortality was observed when the two doses of 1 or 2g/kg day of 50% aqueous ethanolic extract of Cissampelos pareira were administered p.o. for a period of 28 days in rats. There were no significant changes occurred in the blood chemistry analysis including glucose, sodium, potassium, calcium, phosphorus, chloride, total cholesterol, high density lipoprotein, triglycerides, total protein, blood urea nitrogen, creatinine, conjugated billirrubin, aspartate transaminase, alanine transaminase, total billirrubin, albumin, prothrombin time and thromboplastin partial time in both sexes of animals. Hematological analysis showed no marked differences in any of the parameters examined (WBC count, platelet and hemoglobin estimation) in either the control or treated group of both sexes. The urinalysis was negative for glucose, ketonic bodies, casts, red blood cells, and albumin in the control and treatment groups. There were no significant differences in the body and organ weights between controls and treated animals of both sexes. Pathologically, neither gross abnormalities nor histopathological changes were observed. Cissampelos pareira was found safe in acute and subacute toxicities while chronic toxicity studies are further required for the support of the safe and sound use of this traditional plant.

Mucoadhesive Chitosan-Coated Cationic Microemulsion of Dexamethasone for Ocular Delivery: In Vitro and In Vivo Evaluation

ABSTRACT Purpose: Dexamethasone (DXN) is an effective anti-inflammatory drug in the treatment of acute and chronic eye disease such as uveitis. However, its low aqueous solubility limits its clinical usefulness. The purpose of this study was to investigate the mucoadhesive chitosan-coated cationic microemulsions (CH-MEs) for ophthalmic delivery of DXN to treat uveitis. Materials and methods: The pseudo-ternary phase diagrams were developed and various MEs were prepared using isopropyl myristate as oil, Tween 80 as a surfactant, propylene glycol as a co-surfactant and distilled water. MEs were prepared and coated with chitosan by the dropwise addition of chitosan solution in the ME dispersion. Physicochemical parameters (globule size, zetapotential, drug content, viscosity, refractive index and pH), mucoadhesive properties and the in vitro release of MEs were studied. The in vivo efficacy of prepared formulations and the marketed drug solution were studied by administering them topically to endotoxin-induced uveitis rabbit model. Results: All formulations displayed an average globule size less than 200 nm and a positive surface charge. The developed CH-MEs showed acceptable physico-chemical behavior, good mucoadhesive properties, good stability for three months and exhibited sustained drug release. In vivo studies in rabbit eye showed a marked improvement in the anti-inflammatory activity of mucoadhesive CH-ME-treated eye compared with a marketed suspension formulation in a uveitis-induced rabbit eye model. Conclusion: The developed CH-MEs are a viable alternative to conventional eye drops for its ability to enhance bioavailability through its longer precorneal residence time and its ability to sustain the release of the drug.

Hypolipidemic and Antiobesity-Like Activity of Standardised Extract of Hypericum perforatum L. in Rats.

Hypericum perforatum is known to have diverse medicinal uses for centuries. The antidepressant activity of Hypericum perforatum is widely accepted and proved in both animal and clinical studies. Present study was undertaken to investigate the effect of Hypericum perforatum in a battery of animal models for metabolic disorder. Hypericum is tested for hypolipidemic activity in normal rats, antiobesity activity in high-fat-diet induced obese rats, and fructose-fed rats. Hypericum was orally administered as suspension in 0.3% carboxymethyl cellulose at the doses of 100 and 200 mg/kg body weight for 15 consecutive days. Hypericum significantly lowered total cholesterol and low-density cholesterol in normal rats. Hypericum significantly inhibited weight gain in high-fat-fed rats. In fructose-fed rats, Hypericum normalised the dyslipidemia induced by fructose feeding and improved the insulin sensitivity. Taken together, Hypericum could be the antidepressant therapy of choice for patients suffering from comorbid diabetes and obesity.

Antidepressant activity of standardised extract of Marsilea minuta Linn

AIM OF THE STUDY Marsilea minuta Linn. (Marsileaceae) has been referred in Indian traditional medicine system (Ayurveda) for the treatment of insomnia and other mental disorders. Marsiline isolated from Marsilea minuta was reported to have sedative and anticonvulsant property. The ethanol extract of Marsilea minuta was standardised for marsiline (1.15%, w/w) and studied for its antidepressant activity. MATERIALS AND METHODS Antidepressant activity was studied using forced swimming test (FST), tail suspension test (TST), learned helplessness test (LHT) and 5-hydroxytryptophan (5-HTP) induced head twitches response in rodents. Standardised extract of Marsilea minuta in doses of 100, 200 and 400 mg/kg/day were administered orally for three consecutive days and evaluated on day 3, 1h after the last dose treatment. Imipramine (15 mg/kg/day, i.p.) was used as the standard drug. Neurochemical mechanism of antidepressant activity was elucidated by using radioligand receptor binding assays for 5-HT2A and benzodiazepine receptors in rat frontal cortex. RESULTS Immobility time in FST and TST was significantly (P<0.05) reduced by ethanol extract of Marsilea minuta treated animals. A decrease in number of escape failures in LHT was also observed in Marsilea minuta treated rats. Head twitch response induced by 5-HTP was significantly attenuated by Marsilea minuta (400 mg/kg, p.o.) and imipramine showing the involvement of serotonergic system. This effect was corroborated with radioligand receptor binding study where Marsilea minuta (400 mg/kg, p.o.) significantly (P<0.05) down regulated 5-HT2A receptor in frontal cortex, whereas, no marked effect was observed for benzodiazepine receptor. CONCLUSION The antidepressant effect exhibited by Marsilea minuta extract may be due to its effect on 5-HT2A density in rat frontal cortex.

Effect of hydroxypropyl-β-cyclodextrin on the ocular bioavailability of dexamethasone from a pH-induced mucoadhesive hydrogel.

Purpose: Dexamethasone (DXN) is an effective anti-inflammatory drug in the treatment of acute and chronic eye disease such as uveitis. It is relatively lipophilic and permeates biological membranes quite easily. However, its low aqueous solubility limits its clinical usefulness. To circumvent this problem Hydroxypropyl-β-cyclodextrin (HP-β-CD) was used as solubilizer and penetration enhancer for DXN. The purpose of this study was to develop HP-β-CD based pH-induced mucoadhesive hydrogel for ophthalmic delivery of DXN to treat uveitis. Materials and methods: The formation of inclusion complex of DXN with HP-β-CD was characterized in solution and solid states by phase solubility, X-ray diffractometry and IR spectrum analyses. To improve ocular retention and sustained action Carbopol 980 NF and sodium carboxymethylcellulose (NaCMC) were added to the formulations as phase transition and mucoadhesive agents, respectively. Results: The HP-β-CD-based hydrogel system enhanced the solubility of DXN and the apparent stability constant (k′) of the DXN-HP-β-CD inclusion complex was found to be 258.62 M−1. The optimum concentrations of Carbopol 980NF and NaCMC for the mucoadhesive hydrogel were 0.2% (w/v) and 0.4% (w/v), respectively. This mucoadhesive hydrogel could flow freely under non-physiological condition and showed the character of pseudoplastic fluid under both physiological and non-physiological conditions. In vitro release of DXN from the HP-β-CD complex in simulated tear fluid (STF, pH− 7.4), was influenced significantly by the properties and concentration of Carbopol and NaCMC. In vivo studies in rabbit eye showed a marked improvement in anti-inflammatory activity of mucoadhesive hydrogel-treated eye compared with a marketed solution formulation in a uveitis-induced rabbit eye model. Conclusion: The developed HP-β-CD-based mucoadhesive system is a viable alternative to conventional eye drops of DXN due to its ability to enhance bioavailability through its longer precorneal residence time and ability to sustain the release of the drug.

Antidiabetic Activity of Standardized Extract of Quassia amara in Nicotinamide–Streptozotocin-induced Diabetic Rats

The aim of the present study was to evaluate the efficacy of a standardized methanol extract of Quassia amara L. (Family: Simaroubaceae) in nicotinamide–streptozotocin‐induced diabetic rats. Non insulin dependent diabetes mellitus was induced by streptozotocin in rats pre‐treated with nicotinamide. Diabetic rats were treated with oral doses of Quassia amara extract (QaE; 100 and 200 mg/kg) or glibenclamide (10 mg/kg; as standard). QaE and glibenclamide were administered as a suspension in 0.3% carboxy methyl cellulose for 14 days. Control animals received an equal volume of vehicle. Blood samples were collected by retro‐orbital puncture on day 14, 1 h after last treatment. Plasma glucose, insulin and lipid parameters (total cholesterol, LDL‐C, HDL‐C and triglycerides) were measured using commercially available biochemical kits. The oral glucose tolerance test was performed to evaluate the effect of the extract on peripheral glucose utilization in normal rats. Both doses of QaE significantly (p < 0.01) reduced elevated fasting blood glucose levels in diabetic rats. In the oral glucose tolerance test, QaE treatment significantly increased (p < 0.05) the glucose tolerance compared with the vehicle. QaE and glibenclamide, effectively normalized dyslipidemia associated with streptozotocin‐induced diabetes. The findings of the present study indicate that Quassia amara extract may be potentially valuable in the treatment of diabetes and associated dyslipidemia. Copyright

Pharmacognostical Standardization of Withania coagulans Dunal.

Pharmacognostical standardization of fruits of Withania coagulans Dunal. (Solanaceae) has been carried out in the present study. The study includes macroscopical and microscopical evaluation along with estimation of its physicochemical parameters such as ash and extractive values, preliminary phytochemical screening and fluorescence analysis. It also includes quantification of some of the active constituents such as withanolides (withaferin-A) by HPTLC, total phenolic, tannin, flavonoids and flavonols. The present study reveals standardization profile for drug like Withania coagulans, which would be of immense value in botanical identification and authentication of plant drug and may help us in preventing its adulteration.

Evaluation of Cissampelos pareira. Against Gastric Cancer and Enzymes Associated with Carcinogen Metabolism

Abstract The current study is an effort to identify the effect of a hydroalcohol (50% ethanol) extract of roots of Cissampelos pareira. (L.) Hirsuta (Menispermaceae) (CPE) in forestomach cancer and on carcinogen metabolizing phase I and phase II enzymes along with antioxidant enzymes. In forestomach, the activities of glutathione S.-transferase (GST), DT-diaphorase (DTD), and superoxide dismutase (SOD) increased significantly and dose-dependently. The protective effect of CPE was studied against benzo(a.)pyrene [B(a.)P]-induced gastric cancer in mice, and the tumor incidence was reduced and the mean number of tumors and the tumor multiplicity were reduced significantly and dose-dependently. The modulatory effect of CPE was also examined on carcinogen metabolizing phase I and phase II enzymes, antioxidant enzymes, glutathione content, lactate dehydrogenase, and lipid peroxidation in liver. Significant increases in the levels of acid-soluble sulfhydryl (–SH) and cytochrome P450 contents and in enzyme activities of cytochrome P450 reductase, cytochrome b5 reductase, GST, DTD, SOD, catalase, glutathione (GSH) peroxidase, and GSH reductase but decreased malondialdehyde (MDA) were observed. Butylated hydroxyanisole (BHA) showed an increase in hepatic levels of GSH content, cytochrome b5, DTD, GST, glutathione reductase (GR), and catalase, whereas MDA formation was inhibited significantly. BHA also showed increased levels of DTD, GST, and SOD significantly in forestomach. The enhanced GSH level and enzyme activities involved in xenobiotic metabolism and maintaining antioxidant status of cells are suggestive of a chemopreventive efficacy of Cissampelos pareira. against chemotoxicity, including carcinogenicity.

Effect of standardized extract of Marsilea minuta on learning and memory performance in rat amnesic models

Context: Marsilea minuta Linn (Marsileaceae) is a common Indian hydrophytic plant. Traditionally, the plant has been used as a sedative for the treatment of insomnia and other mental disorders. Background information of this plant has encouraged us to investigate its antiamnesic activity in rat. Objective: Standardized ethanol extract of M. minuta was investigated for their putative role in learning and memory performance in normal and amnesic rats. Materials and methods: Ethanol extract of M. minuta (EMM) was standardized for marsiline using HPLC. The effect of standardized extract of M. minuta (1.15% w/w marsiline) was tested in amnesic rat using elevated plus maze (EPM) and passive avoidance (PA) test. Amnesia was induced after scopolamine (1 mg/kg, s.c.) and electroconvulsive shock (150 mA, 0.2 s) treatment. Behavioral studies were further substantiated with acetylcholinesterase (AChE) activity and radioligand muscarinic receptor binding studies in rat brain regions. Results: Oral administration of EMM at 200 and 400 mg/kg/day for 3 days significantly reversed the amnesia whereas, no per se effect was observed. In comparison to control, AChE activity in frontal cortex and hippocampus was found to be significantly (P < 0.05) inhibited by EMM. EMM at doses 200 and 400 mg/kg has significantly (P < 0.05) increased (+34 % and +40 % change in affinity, respectively) the binding of 3H-QNB in frontal cortex indicating the up regulation of the muscarinic receptors. Discussion and conclusion: These findings suggest that standardized extract of M. minuta have excellent antiamnesic activity, probably mediating through central cholinergic system.