Rivaroxaban-loaded SLNs with treatment potential of deep vein thrombosis: in-vitro, in-vivo, and toxicity evaluation.

OBJECTIVES: Rivaroxaban (RXB), a novel Xa inhibitor having groundbreaking therapeutic potential. However, this drug is associated with few limitations, including its pharmacokinetics related toxicities. Here, we developed RXB-loaded SLNs (RXB-SLNs) to improve its biopharmaceutical profile. Methods: High pressure homogenizer was used to prepare RXB-SLNs, followed by their particle characterization, Transmission electron microscopy (TEM), Dynamic light scattering (DSC), and Powder X-ray diffraction (PXRD) analysis. Beside this, in-vitro, ex-vivo, and in-vivo evaluation, prothrombin time assessment and toxicity was investigated. RESULTS: RXB-SLNs had their particle size in nano range (99.1 ± 5.50 nm) with excellent morphology and low polydispersity index (0.402 ± 0.02) and suitable zeta potential (-25.9 ± 1.4 mV). The incorporation efficiency was observed around 95.9 ± 3.9%. In-vitro release profiles of the RXB-SLNs exhibited enhanced dissolution (89 ± 9.91%) as compared to pure drug (11 ± 1.43%) after 24 h of the study. PK study demonstrated a seven times enhanced bioavailability of RXB-SLNs when compared with pure drug. Furthermore, RXB-SLNs exhibited an expressive anti-coagulant behavior in human and rat blood plasma. Also, the final formulation exhibited no toxicity after oral administration of the SLNs. CONCLUSIONS: All together, these studies revealed the capability of the SLNs for carrying the RXB with enhanced therapeutic efficacy and no toxicity, most importantly for the treatment of deep vein thrombosis.

Anti-diabetic and spasmolytic potential of Farsetia hamiltonii Royle from Cholistan desert.

ETHNOPHARMACOLOGICAL RELEVANCE: Folk herbal practitioners of the Cholistan desert claim Farsetia hamiltonii Royle (Brassicaceae) to treat diabetes, oxidative damages, diarrhea, fever, and abdominal cramps. The aim of this study was to scientifically find the potential of Farsetia hamiltonii in treating diabetes and gastrointestinal diseases. MATERIALS AND METHODS: In vivo anti-diabetic activity of Farsetia hamiltonii was studied on alloxan induced diabetic rats to justify its traditional use. The in vitro antispasmodic activity on isolated tissues of rabbit jejunum was also evaluated. In addition, several enzyme inhibition studies (lipoxygenase, tyrosinase, acetylcholinesterase (AchE), carbonic II anhydrase and phosphodiesterase I) and antioxidant activity of plant extracts were also conducted. RESULTS: In vivo experiments, Farsetia hamiltonii methanol extract (300 mg/kg) significantly lowered the fasting blood glucose (107.6 ± 1.249 mg/dL up to 4th day) comparable to positive control (Glibenclamide) throughout the study period. The in vitro antispasmodic activity on isolated tissues of rabbit jejunum on methanol extract showed concentration dependent (0.01-0.3 mg/ml) relaxation of spontaneous contractions with EC50 value 0.011 µM and high K(+) (80 mM) induced contraction (0.01-0.1 mg/ml) with EC50 value 0.066 mg/ml. Farsetia hamiltonii DCM and methanol extracts exhibited some antilipoxygenase activities while tyrosinase, acetylcholinesterase (AchE), carbonic II anhydrase, phosphodiesterase I, and antioxidant activity of plant extracts were not significant. CONCLUSIONS: Our results validate the traditional use of Farsetia hamiltonii for the traditional therapeutic potential in treating diabetes and gastrointestinal diseases.

Callogenic studies of Achyranthes aspera leaf explant at different hormonal combinations.

With the objective to promote in vitro callus induction, leaf segments of Achyranthes aspera were inoculated on basal MS medium supplemented with 3.0% sucrose and 0.8% agar with different concentrations of 2,4-D alone and in combination with NAA, BAP, IAA, IBA and Zeatin. The explants were maintained in growth room at 25 +/- 1 degrees C and 16 h light cycle. The best callus induction was obtained with 2,4-D (1.0 and 2.0 mg L(-l)) in combination with NAA (0.5 mg L(-1)). Callus induction and good texture from leaf explant was also observed at 2,4-D with BAP. On these combinations morphologically, light green, soft, compact and non-embryogenic callus (Type III callus) was observed. While morphology of callus and callogenic response was poor at 2,4-D alone or in combination with other hormones at different concentrations.