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Karan S.K.,Seemanta Institute of Pharmaceutical science | Mondal A.,Indian Institute of Chemical Technology | Mishra S.K.,Utkal University | Pal D.,SLT Institute of Pharmaceutical science | Rout K.K.,Indian Institute of Chemical Technology
Pharmaceutical Biology | Year: 2013

Context: In the Indian traditional system of medicine, Streblus asper Lour (Moraceae) is prescribed for the treatment of diabetes mellitus. Objective: In the present study, α-amyrin acetate isolated from S. asper, and the petroleum ether extract of S. asper stem bark (PESA) was screened for their antidiabetic properties in streptozotocin (STZ)-induced diabetic rats. Materials and methods: Successive Soxhlet extraction of the dried stem bark with petroleum ether and then with ethanol (95%) yielded petroleum ether and ethanol extracts, respectively, which were concentrated under reduced pressure. Hyperglycemia was induced in rats by STZ (50mg/kg, b.w.). Twenty-four hours after STZ induction, respective groups of diabetic rats received PESA (100, 250 and 500mg/kg, b.w.) and α-amyrin acetate (25, 50 and 75mg/kg, b.w.) respectively, orally daily for 15 days. Glibenclamide (0.5mg/kg, orally) served as a reference. Blood glucose levels were measured on every 5th day during the 15 days of treatment. The serum lipid profiles and biochemical parameters, viz., serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP), insulin and glycosylated hemoglobin level, were measured. Results: PESA significantly (p < 0.01) normalized blood-glucose levels and serum biochemical parameters as compared with those of STZ controls. α-Amyrin acetate (75mg/kg, b.w.) exhibited maximum glucose lowering effect (71.10%) in diabetic rats compared to the other dose (25, 50mg/kg) at the end of the study. The protective effect was further confirmed by histopathological examination of the liver. Conclusion: PESA and α-amyrin acetate demonstrated remarkable antidiabetic activity in STZ-induced diabetic rats. © 2013 Informa Healthcare USA, Inc. Source

Pandey R.S.,SLT Institute of Pharmaceutical science | Jain V.,Famycare Ltd | Katare O.P.,Panjab University | Chandra R.,University of Delhi | Katyal A.,University of Delhi
Nanomedicine: Nanotechnology, Biology, and Medicine | Year: 2013

Noscapine crosses blood-brain-barrier and inhibits proliferation of glioblastoma cells. However, short plasma half-life and rapid elimination necessitate the administration of multiple injections for successive chemotherapy. Noscapine bearing solid lipid nanoparticles, Nos-SLN and poly (ethylene)-glycol conjugated solid lipid nanoparticles of noscapine, Nos-PEG-SLN of 61.3±9.3-nm and 80.5±8.9-nm containing 80.4±3.2% and 83.6±1.2% of Nos, were constructed. First order kinetic and Higuchi equation were followed to release the Nos at intracellular pH~4.5. Further, a decrease in IC50 (Nos; 40.5μM>Nos-SLN; 27.2μM>20.8μM) and enhanced subG1 population were observed in U87cells. Plasma half-life was enhanced up to ~11-fold and ~5-fold by Nos-PEG-SLN and Nos-SLN which significantly (P<0.05) deposits 400.7μg/g and 313.1μg/g of Nos in comparison to 233.2μg/g by drug solution. This is first report demonstrating a workable approach to regulate the administration of multiple injections of Nos, warranting further in vivo tumor regression study for superior management of brain cancer. From the Clinical Editor: This report describes a possible approach to regulate the administration of multiple injections of Noscapine using solid lipid nanoparticles. The data warrant further in vivo tumor regression studies for optimal management of glioblastoma, a generally very poorly treatable brain cancer. © 2013 Elsevier Inc. Source

Madan J.,Georgia State University | Pandey R.S.,SLT Institute of Pharmaceutical science | Katare O.P.,Panjab University | Aneja R.,Georgia State University | Katyal A.,University of Delhi
Colloids and Surfaces B: Biointerfaces | Year: 2013

Noscapine, recently identified as anticancer due to its microtubule-modulating properties. It is presently in Phase I/II clinical trials. The therapeutic efficacy of noscapine has been established in several xenograft models. Its pharmacokinetic limitations such as low bioavailability and high ED50 impede development of clinically relevant treatment regimens. Here we present design, synthesis, in vitro and in vivo characterization of sterically stabilized gelatin microassemblies of noscapine (SSGMS) for targeting human non-small cell lung cancer A549 cells. The average size of the sterically stabilized gelatin microassemblies of noscapine, SSGMS was 10.0±5.1μm in comparison to noscapine-loaded gelatin microassemblies, GMS that was 8.3±5.5μm. The noscapine entrapment efficiency of SSGMS and GMS was 23.99±4.5% and 24.23±2.6%, respectively. Prepared microassemblies were spherical in shape and did not show any drug and polymer interaction as examined by FTIR, DSC and PXRD. In vitro release data indicated that SSGMS and GMS follow first-order release kinetics and exhibited an initial burst followed by slow release of the drug. In vitro cytotoxicity evaluated using A549 cells showed a low IC50 value of SSGMS (15.5μM) compared to GMS (30.1μM) and free noscapine (47.2μM). The SSGMS can facilitate a sustained therapeutic effect in terms of prolonged release of noscapine as evident by caspase-3 activity in A549 cells. Concomitantly, pharmacokinetic and biodistribution analysis showed that SSGMS increased the plasma half-life of noscapine by ∼9.57-fold with an accumulation of ∼48% drug in the lungs. Our data provides evidence for the potential usefulness of SSGMS for noscapine delivery in lung cancer. © 2013 Elsevier B.V. Source

Jain V.,Chouksey Engineering College | Jain B.,Chouksey Engineering College | Tiwari P.,Chouksey Engineering College | Pandey R.S.,SLT Institute of Pharmaceutical science | And 3 more authors.
Anti-Cancer Drugs | Year: 2013

About 10% of the drugs in the preclinical stage are poorly soluble, 40% of the drugs in the pipeline have poor solubility, and even 60% of drugs coming directly from synthesis have aqueous solubility below 0.1 mg/ml. Out of the research around, 40% of lipophilic drug candidates fail to reach the market despite having potential pharmacodynamic activities. Microtubule-modulating chemotherapeutics is an important class of cancer chemotherapy. Most chemotherapeutics that belong to this category are plant-derived active constituents, such as vincristine, vinblastine, colchicine, docetaxel, paclitaxel, and noscapinoids. The pKa of a drug considerably affects its solubility in physiological fluids and consequently bioavailability. It usually ranges from 5 to 12 for microtubule-modulating drugs. Hence, the solubility of these drugs in physiological fluids is considerably affected by a change in pH. However, because of unpredictable parameters involved in poor solubility and the low oral bioavailability of these chemotherapeutics during the early phases of drug development, they often have an unusual pharmacokinetic profile. This makes the development process of novel chemotherapeutics slow, inefficient, patient-unfriendly, and very costly, emphasizing a need for more rational approaches on the basis of preclinical concepts. Nanosolvation is a process of increasing the polarity of a hydrophobic molecule either by solvation or cavitization in a hydrophilic macrocycle. The present review therefore focuses on the techniques applied in nanosolvation of microtubule-modulating chemotherapeutics to enhance solubility and bioavailability. The methodologies described will be highly beneficial for anticancer researchers to follow a trend of rational drug development. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source

Namdeo K.P.,SLT Institute of Pharmaceutical science | Shrivastava S.K.,Banaras Hindu University
Asian Journal of Chemistry | Year: 2011

The synthesis and evaluation of anticonvulsant activity of prodrugs of gabapentin are reported by taking the dihydropyridine compound as carrier molecules, in redox delivery approach. A redox system of drug delivery based on an interconvertible dihydropyridine ⇌ pyridinium salt carrier. Anticonvulsant activity of all the compounds were tested by chemo-convulsion method and all the compounds found active. All the compounds were also studied for oxidation in various biological fluids and found to be stable and shows sustained release profile which follow first order kinetics. Oxidized form of the conjugate inside the brain act as prodrug, which on hydrolysis yields parent drug. Source

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