Cyclodextrin Complexes of Reduced Bromonoscapine in Guar Gum Microspheres Enhance Colonic Drug Delivery

Here, we report improved solubility and enhanced colonic delivery of reduced bromonoscapine (Red-Br-Nos), a cyclic ether brominated analogue of noscapine, upon encapsulation of its cyclodextrin (CD) complexes in bioresponsive guar gum microspheres (GGM). Phase−solubility analysis suggested that Red-Br-Nos complexed with β-CD and methyl-β-CD in a 1:1 stoichiometry, with a stability constant (Kc) of 2.29 × 103 M−1 and 4.27 × 103 M−1. Fourier transforms infrared spectroscopy indicated entrance of an O−CH2 or OCH3−C6H4−OCH3 moiety of Red-Br-Nos in the β-CD or methyl-β- CD cavity. Furthermore, the cage complex of Red-Br-Nos with β-CD and methyl-β-CD was validated by several spectral techniques. Rotating frame Overhauser enhancement spectroscopy revealed that the Ha proton of the OCH3−C6H4−OCH3 moiety was closer to the H5 proton of β-CD and the H3 proton of the methyl-β-CD cavity. The solubility of Red-Br-Nos in phosphate buffer saline (PBS, pH ∼ 7.4) was improved by ∼10.7-fold and ∼21.2-fold when mixed with β-CD and methyl-β-CD, respectively. This increase in solubility led to a favorable decline in the IC50 by ∼2-fold and ∼3-fold for Red-Br-Nos−β-CD-GGM and Red-Br-Nos−methyl-β-CD-GGM formulations respectively, compared to free Red-Br-Nos−β-CD and Red-Br-Nos−methyl-β-CD in human colon HT-29 cells. GGM-bearing drug complex formulations were found to be highly cytotoxic to the HT-29 cell line and further effective with simultaneous continuous release of Red-Br-Nos from microspheres. This is the first study to showing the preparation of drug-complex loaded GGMS for colon delivery of Red-Br-Nos that warrants preclinical assessment for the effective management of colon cancer

Development and Validation of Stability Indicating UV-visible Spectrophotometric Method for Simultaneous Determination of Salbutamol Sulphate and Ambroxol Hydrochloridein Liquid Dosage Form

Purpose: A new, simple, precise and validated UV spectrophotometric method has been developed for simultaneous estimation of salbutamol sulphate and ambroxol hydrochloride in liquid dosage form. Method: The method employed was simultaneous equation method which involves solving simultaneous equations based on measurement of absorbance at two wavelengths 224 nm and 244 nm, the λmax of salbutamol sulphate and ambroxol hydrochloride, respectively. Specificity of the method was determined by subjecting the drugs to various stress conditions like acid, alkali, thermal and photolytic degradation. Results: The linearity was obtained in the concentration range of 0.1-0.6 μg/mL for salbutamol sulphateand 1.5-09 μg/mL for ambroxol hydrochloride. The proposed method was effectively applied to liquid dosage form for estimation of both drugs. The accuracy and reproducibility results are close to 100% with ≤2% RSD. The results of proposed method have been validated as per ICH guidelines. Conclusion: A novel, precise and accurate stability indicating spectrophotometric method has been developed for the estimation of salbutamol sulphate and ambroxol hydrochloride in pharmaceutical syrup formulation

High confidence QTLs and key genes identified using Meta-QTL analysis for enhancing heat tolerance in chickpea (Cicer arietinum L.)

The rising global temperatures seriously threaten sustainable crop production, particularly the productivity and production of heat-sensitive crops like chickpeas. Multiple QTLs have been identified to enhance the heat stress tolerance in chickpeas, but their successful use in breeding programs remains limited. Towards this direction, we constructed a high-density genetic map spanning 2233.5 cM with 1069 markers. Using 138 QTLs reported earlier, we identified six Meta-QTL regions for heat tolerance whose confidence interval was reduced by 2.7-folds compared to the reported QTLs. Meta-QTLs identified on CaLG01 and CaLG06 harbor QTLs for important traits, including days to 50% flowering, days to maturity, days to flower initiation, days to pod initiation, number of filled pods, visual score, seed yield per plant, biological yield per plant, chlorophyll content, and harvest index. In addition, key genes identified in Meta-QTL regions like Pollen receptor-like kinase 3 (CaPRK3), Flowering-promoting factor 1 (CaFPF1), Flowering Locus C (CaFLC), Heat stress transcription factor A-5 (CaHsfsA5), and Pollen-specific leucine-rich repeat extensins (CaLRXs) play an important role in regulating the flowering time, pollen germination, and growth. The consensus genomic regions, and the key genes reported in this study can be used in genomics-assisted breeding for enhancing heat tolerance and developing heat-resilient chickpea cultivars

Systemic and pulmonary hemodynamics in patients with extrahepatic portal vein obstruction is similar to compensated cirrhotic patients

Background: Patients with cirrhosis and portal hypertension exhibit a hyperdynamic circulation manifesting as increased cardiac output, heart rate and plasma volume; and decreased arterial blood pressure, systemic vascular resistance, and pulmonary vascular resistance. It is believed that these changes are related to both hepatocellular dysfunction and portal hypertension. However, the role of portal hypertension per se in producing these changes in circulation has not been clear. Extrahepatic portal vein obstruction (EHPVO), a vascular disorder of the liver characterized by cavernomatous transformation of the main portal vein, is an excellent model to study the role of portal hypertension per se in producing these changes because there is no hepatic dysfunction in EHPVO. The main aim of our study was, therefore, to evaluate alterations of systemic and pulmonary vascular systems in patients with EHPVO and compare them with patients with compensated cirrhosis. Patients and methods: Consecutive patients of EHPVO, 15 years or older, and past variceal bleeders were studied. For comparison, consecutive patients with compensated cirrhosis and history of variceal bleed, matched for variceal status, and body surface area were included. The hemodynamic studies included the measurements of cardiac index (by Fick's oxygen method), and systemic and pulmonary vascular resistance indices. Results: Fifteen patients of EHPVO and same number of controls (compensated cirrhotics) were included in the study. The baseline parameters in the two groups were comparable. Both EHPVO patients and cirrhotics had similar values in all the measured systemic and pulmonary hemodynamic parameters. The median (range) cardiac index in EHPVO was 3.8 (2.3-7.7) l min-1 m-2, whereas it was 4.4 (2.8-8.9) l min-1 m-2 in cirrhosis (P = 0.468). The median (range) systemic vascular resistance index in EHPVO was 1,835 (806-3400) dyne s cm-5 m-2, which was similar to that in cirrhotic patients (1,800 [668-3022], P = 0.520). Similarly, the values of median (range) pulmonary vascular resistance index were comparable in the two groups (71 [42-332] vs. 79 [18-428], P = 0.885). A subgroup analysis was done for 8 patients of EHPVO and 8 age-matched compensated cirrhotic patients, which also revealed similar values of cardiac index, cardiac output, systemic vascular resistance index, systemic vascular resistance, pulmonary vascular resistance index, and pulmonary vascular resistance in the two groups. Conclusions: EHPVO patients have hyperdynamic circulation manifested by high cardiac index and low systemic and pulmonary vascular resistance indices. These hemodynamic changes are comparable with compensated cirrhotic patients who have similar grade of portal hypertension. This suggests a predominant role of portal hypertension per se in the genesis of systemic and pulmonary hemodynamic alterations