6-SHOGAOL RICH GINGER OLEORESIN LOADED MIXED MICELLES ENHANCES IN VITRO CYTOTOXICITY ON MCF-7 CELLS AND IN VIVO ANTICANCER ACTIVITY AGAINST DAL CELLS

Objective: Ginger oleoresin (GO) plays an important role on the attenuation of complications associated to the cancer which is attributed to 6-shogaol (6-SGL). The major challenge in using 6-SGL for therapeutic applications is its poor aqueous solubility, low stability in GI and low bioavailability. Considering the potent anticancer nature of 6-SGL and its synergistic activity with other constituents in GO, there is a need to develop a suitable drug delivery system.Methods: Thus in the present study, 6-SGL rich GO (6-SRGO) was incorporated into mixed micelles using phospholipid (Soya Lecithin) as a carrier. The prepared 6-SRGO loaded mixed micelles (6-SRGO-LMM) were characterized physically and chemically using Fourier transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC) and further evaluated for stability study, in vitro release study, in vitro cytotoxicity study and in vivo anticancer activity in comparison with 6-SRGO.Results: The composition such as, drug content (86.27±1.56), encapsulation efficiency (81.55±1.05) and particle size (356.11±4.07) were optimized using 32 factorial design. FTIR and DSC study confirm that the 6-SGL from 6-SRGO was entrapped in the core of phospholipid by self-assembly method to form mixed micelles. The 6-SRGO-LMM exhibited significant in vitro (GI50-23.2 μg/ml) and in vivo anticancer activity in comparison with 6-SRGO.Conclusion: We have developed and investigated mixed micelles composed of phospholipids (soya lecithin S80) and SCH as an effective nanocarrier for the delivery of a natural lipophilic anticancer bioactive 6-SGL from 6-SRGO

THERMOSENSITIVE IN SITU GEL OF TINIDAZOLE IN TREATMENT OF BACTERIAL VAGINOSIS: FORMULATION AND EVALUATION

Bacterial Vaginosis (BV) is the leading cause of vaginal discharge. Because of its big surface area, wealthy blood supply, avoidance of the first-pass effect and high permeability to many drugs, the vagina offers a promising location for local impact as well as systemic drug delivery. In situ gels give several benefits, such as ease of administration in the respective body cavities, elevated spreadability at certain temperatures, reduced administration frequency, improved patient compliance and comfort compared to standard dosage forms. Tinidazole (TNZ) can give effective treatment over the BV. In situ gel of TNZ containing polaxomer 407 and HPMC E100 or carbopol 941NF was optimized on the basis of various evaluation parameters. Gelation temperature (Tgel) and pH of all batches was found in range of 36.6 to 38.0 ºC and 4.20 to 5.03, viscosity was found in range of 1100-2050 cps at 25ºC and 4800-6530 cps at 37ºC. The Spredability was found in range of 16-20 cm. From these evaluation parameters we selected best combination for the mucoadhesive property, antimicrobial study, in vitro drug release and for HET CAM irritation study. The optimized formulation gives satisfactory results. In this study we also compare the performance of two mucoadhesive polymer. Based on maximum desirability and cost effectiveness, in situ vaginal gel containing 20% polaxomer and 0.5% HPMC E100 could be considered as a highly promising treatment for bacterial vaginosis

Priprava i evaluacija plutajućih matriksa rizedronat natrija Gelucire® 39/01

Incorporation of bisphosphonates in the lipid reduces gastric irritation. Only gastric retention with sustained release allows the drug to reach the duodenum and jejunum and improves the availability of bisphosphonates. Risedronate sodium and Gelucire® 39/01 floating matrices were prepared using melt solidification. The sustained release floating matrices were evaluated for in vitro and in vivo floating ability and in vitro drug release. Ageing of the matrices was studied by differential scanning calorimetry, hot stage polarizing microscopy, scanning electron microscopy and in vitro drug release. Ageing causes changes in the crystal structure of the Gelucire®, which is responsible for increase in drug release.Uklapanje bisfosfonata u lipide smanjuje iritaciju želuca. Samo zadržavanje u želucu s usporenim oslobađanjem omogućava da ljekovita tvar dospije u duodenum i jejunum i povećava bioraspoloživost bisfosfonata. Rizedronat natrij i Gelucire® 39/01 plutajući matriksi pripravljeni su metodom taljenja i očvršćivanja. Proučavana je sposobnost plutanja pripremljenih matriksa in vitro i in vivo te oslobađanje ljekovite tvari. Starenje matriksa proučavano je diferencijalnom pretražnom kalorimetrijom, polarizirajućom mikroskopijom s vrućom pločom i pretražnom elektronskom mikroskopijom. Starenje uzrokuje promjene u kristalnoj strukturi Gelucire® zbog kojih se povećava oslobađanje ljekovite tvari

Comparative antioxidant potential of Withania somnifera based herbal formulation prepared by traditional and non-traditional fermentation processes

AbstractBackgroundAshwagandharishtha is a liquid polyherbal formulation traditionally prepared by fermentation process using the flowers of Woodfordia fruticosa. It contains roots of Withania somnifera as a major crude drug. Alcohol generated during the fermentation causes the extraction of water insoluble phytoconstituents. Yeasts present on the flowers are responsible for this fermentation.MethodsTotal nine formulations of ashwagandharishtha were prepared by fermentation process using traditional Woodfordia fruticosa flowers (ASG-WFS) and using yeasts isolated from the same flowers. During fermentation, kinetic of alcohol generation, sugar consumption, changes in pH and withanolides extraction were studied. All the formulations were tested for in vitro antioxidant potential by 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical scavenging, hydrogen peroxide scavenging and total reducing power assay. The results were compared with standard ascorbic acid.ResultsTraditional formulation (ASG-WFS) showed the highest activity (p < 0.001) relative to other formulations and standard ascorbic acid. ASG-WFS showed significant (DPPH) free radical scavenging (78.75%) and hydrogen peroxide scavenging (69.62%) at the concentration of 1000μg/mL and 100μg/mL, respectively.ConclusionTraditional process is the best process for preparing ashwagandharishtha to obtain significant antioxidant activity

Hypoglycemic and Hypolipidemic Effect of Sida rhombifolia ssp. retusa in Diabetic Induced Animals

In the present study, the anti-diabetic effect of aqueous extract of Sida rhombifolia ssp. retusa (Malvaceae) leaves was studied in normal and streptozotocin (STZ)-induced (60 mg/kg, single intraperitoneal injection) diabetic rats. Hypoglycemic activity in normal rats was tested after administration of 200 mg/kg of extract.Aqueous extract showed a 15% reduction in plasma glucose level after 1.5 h of extract administration. When tested in STZ-induced diabetic rats the reduction in plasma glucose was 17%. In oral glucose tolerance test in normal rats and STZ-induced rats the decrease in AUC was 15 and 7% respectively. Glibenclamide was used as reference drug and showed significant hypoglycemic effects in normal rats but had marginal activity in STZ-induced diabetic rats. In hypolipidemic study a dose of 200 mg/kg of aqueous extract has shown reduction in triglycerides (TG) (16%), cholesterol (4%), and glucose level (10%). Fenofibrate was used as standard drug for hypolipidemic study.The results obtained from the experiment provided scientific evidence in favor of the traditional use of Sida rhombifolia ssp. retusa leaves for the treatment of diabetes mellitus.Keywords: Diabetes, Sida rhombifolia ssp. Retusa, hypoglycemic activity and hypolipidemic activity

SYNTHESIS AND ANTICANCER SCREENING OF TRIAZINE ANALOGUES

Objective: The study was aimed to investigate the cytotoxic effect of S-5H-[1,2,4]-triazino (5,6-b) indol-3-yl-3,4-phenylethane-thioate derivatives as epidermal growth factor Receptor (EGFR) inhibitors. Methods: In the present study 14 novel triazine analogues were synthesized and characterized using different spectroscopic techniques such as FT-IR, NMR and Mass Spectroscopy. The anticancer activity was performed using MCF-7 (breast cancer) and K-562 (leukaemia) cell lines. Further, molecular docking was carried out using Vlife Molecular Docking Software (MDS) on crystal structure of epidermal growth factor receptor (EGFR) to identify the binding mode of interaction with an active site. Results: Compounds MA-7, MA-8, MA-12, MA-13 and MA-14 show potent activity against cancer cell lines in the range of&lt;10 to 84.4 µg/ml. Further molecular docking on EGFR also supports that there is a strong correlation between in silico and in vitro biological activity. The results of this study may be further useful for lead optimization process. Conclusion: The results of this study indicates that the synthesized triazine analogues can give a potential lead as an anticancer agent

Effect of pH and Gastrointestinal Enzymes on Stability of Psoralen, Bakuchicin and Bakuchiol using Simultaneous TLC Densitometric Method and Standardization of commercial formulations containing Psoralea cordyfollia Linn.

Psoralea corylifolia is used for treatmet of skin diseases such as psoriasis, vitiligo. Psoralen is responsible for its effectiveness against psoriasis. Bakuchicin and Bakuchiol are DNA polymerase and topoisomerase II inhibitors. To study the effect of pH and gastrointestinal (GI) enzymes on Psoralen, Bakuchicin and Bakuchiol from Psoralea corylifolia Linn using a simple, sensitive, accurate and robust high performance thin layer chromatographic (HPTLC) method. The method was performed on silica gel 60 F254with n- Hexane : Ethyl acetate ( 7.5 : 2.5 v/v)&nbsp; as the mobile phase. Densitometric scanning at 285 nm for Psoralen, Bakuchicin and Bakuchiol was used. The method was validated as per the guidelines of International Conference on Harmonization (ICH). In addition the applicability of the method was tested for the standardization of both mono and polyherbal formulations containing the above markers. The Rf values of 0.37, 0.48 and 0.63 were obtained for Psoralen, Bakuchicin and Bakuchiol respectively. The linearity range of 20-120 ng spot-1,&nbsp; 20-120 ng spot-1 and 80-280 ng spot-1&nbsp; with good correlation coefficients of r2 = 0.998, 0.998 and 0.999 were obtained for Psoralen, Bakuchicin and Bakuchiol&nbsp; respectively. The method was applied for the in vitro stability studies of above markers in simulated gastric and intestinal fluids to study the effect of pH and GI enzymes. Psoralen was found to be most stable in the simulated physiological fluids whereas other two compounds showed instability. The method was found to be precise, robust and suitable for the routine quality control analysis of plant extracts and polyherbal formulations. Keywords: Psoralea corylifolia Linn, Leguminoceae, HPTLC, Enzymatic stabilit

Rectal gel application of Withania somnifera root extract expounds anti-inflammatory and muco-restorative activity in TNBS-induced Inflammatory Bowel Disease

<p>Abstract</p> <p>Background</p> <p>Inflammatory Bowel Disease (IBD) is marked with chronic inflammation of intestinal epithelium driven by oxidative stress. Traditional treatments with plant extracts gained renewed interest due to their ability to ameliorate the multi factorial conditions like inflammation. We investigated the beneficial effects of <it>Withania somnifera </it>in Trinitro Benzyl Sulfonic Acid (TNBS) induced experimental IBD through a rectally applicable formulation.</p> <p>Methods</p> <p>The study included (i) preparation of gel formulation from aqueous <it>Withania somnifera </it>root extract (WSRE), (ii) biochemical assays to determine its performance potential, (iii) testing of formulation efficacy in TNBS-induced IBD rat model, and (iv) histo-patholgical studies to assess its healing and muco-regenerative effect in IBD-induced rats. For this purpose, concentration dependant antioxidant activity of the extracts were evaluated using biochemical assays like (a) inhibition of lipid peroxidation, (b) NO scavenging, (c) H₂O₂scavenging, and (d) ferric reducing power assay.</p> <p>Results</p> <p>The extract, at 500 μg/ml, the highest concentration tested, showed 95.6% inhibition of lipid peroxidation, 14.8% NO scavenging, 81.79% H₂O₂scavenging and a reducing capacity of 0.80. The results were comparable with standard antioxidants, ascorbic acid and curcumin. WSRE treatment positively scored on histopathological parameters like necrosis, edema, neutrophil infiltration. The post treatment intestinal features showed restoration at par with the healthy intestine. In view of these results, gel formulation containing an aqueous extract of <it>W. somnifera</it>, prepared for rectal application was tested for its anti-inflammatory activity in TNBS-induced rat models for IBD. Commercially available anti-inflammatory drug Mesalamine was used as the standard in this assay.</p> <p>Conclusions</p> <p>Dose of the rectal gel applied at 1000 mg of WSRE per kg rat weight showed significant muco-restorative efficacy in the IBD-induced rats, validated by histo-pathological studies.</p