Abstract. The purpose of this research was to generate, characterize, and investigate the in vivo efficacy of budesonide (BUD) microparticles prepared by spray-drying technology with a potential application as carriers for pulmonary administration with sustained-release profile and improved respirable fraction. Microspheres and porous particles of chitosan (drug/chitosan, 1:2) were prepared by spray drying using optimized process parameters and were characterized for different physicochemical parameters. Mass median aerodynamic diameter and geometric standard deviation for conventional, microspheres, and porous particles formulations were 2.75, 4.60, and 4.30 µm and 2.56, 1.75, and 2.54, respectively. Pharmacokinetic study was performed in rats by intratracheal administration of either placebo or developed dry powder inhalation (DPI) formulation. Pharmacokinetic parameters were calculated (Ka, Ke, T max , C max , AUC, and Vd) and these results indicated that developed formulations extended half life compared to conventional formulation with onefold to fourfold improved local and systemic bioavailability. Estimates of relative bioavailability suggested that developed formulations have excellent lung deposition characteristics with extended T 1/2 from 9.4 to 14 h compared to conventional formulation. Anti-inflammatory activity of BUD and developed formulations was compared and found to be similar. Cytotoxicity was determined in A549 alveolar epithelial cell line and found to be not toxic. In vivo pulmonary deposition of developed conventional formulation was studied using gamma scintigraphy and results indicated potential in vitro-in vivo correlation in performance of conventional BUD DPI formulation. From the DPI formulation prepared with porous particles, the concentration of BUD increased fourfold in the lungs, indicating pulmonary targeting potential of developed formulations.
Objectives:To evaluate the prolongation of ventricular repolarization and proarrhythmic activity of antimalarial drug chloroquine in two rabbit proarrhythmia models viz., in vivo α1 adrenoceptor-stimulated anesthetized rabbit and ex vivo isolated Langendorff rabbit heart using clofilium as standard proarrhythmic agent.Materials and Methods:In the in vivo model, three groups of rabbits, anesthetized by pentobarbitone sodium and α-chloralose, sensitized with α1 agonist methoxamine followed by either continuous infusion of saline (control) or clofilium (3 mg/kg) or chloroquine (21 mg/kg) for 30 min. In ex vivo model, rabbit hearts were perfused with clofilium (10 μM) or chloroquine (300 μM) continuously after priming along with methoxamine, acetylcholine chloride and propranolol hydrochloride.Results:In these models, prolongation of repolarization during α1-adrenoceptor stimulation produced early after depolarization (EAD) and Torsade de pointes (TdP). Saline infusion did not induce any abnormality in the animals. Clofilium caused expected changes in the electrocardiogram in both the models including TdP (50.0% in in vivo and 66.67% in ex vivo). Chloroquine caused decrease in heart rate and increase in the corrected QT (QTc) interval in both the models. Further, apart from different stages of arrhythmia, TdP was evident in 33.33% in ex vivo model, whereas no TdP was observed in in vivo model.Conclusions:The results indicated that proarrhythmic potential of chloroquine and clofilium was well evaluated in both the models; moreover, both the models can be used to assess the proarrhythmic potential of the new drug candidates.
Curcumin is a well-recognized antioxidant phytoactive isolated from the rhizomes of
Curcuma longa
. Numerous landmark investigations have proved the antioxidant and hepatoprotective potential of curcumin. The aim of present study was to target curcumin loaded nanocarriers to hepatocytes using asialoglycoprotein receptors targeting strategy. Mannose, a water-soluble carbohydrate, was hydrophobized by anchoring stearylamine with an objective to conjugate mannose on the surface of curcumin loaded nanostructured lipid carriers for targeting asialoglycoprotein receptors on hepatocytes. Mannose conjugated stearylamine was synthesized and characterized using various analytical techniques. The synthesized targeting ligand was incorporated curcumin loaded nanostructured lipid carriers and characterized by photon correlation spectroscopy. Zeta potential measurement was used to confirm the conjugation of the synthesized ligand to the surface of drug-loaded nanostructured lipid carriers. CCl
4
induced hepatotoxicity in male Wistar rats was used as an experimental animal model to evaluate the hepatoprotective potential of formulated drug encapsulated nanostructured lipid carriers. The hepatoprotective potential was assessed by measuring serum liver injury markers and oxidative stress parameters in the liver post–mitochondrial supernatant. Mannose conjugated nanostructured lipid carriers showed acceptable particle size which revealed its suitability for hepatocyte targeting. In addition to this, mannose conjugated nanocarriers revealed significantly better (p < 0.05) reduction of serum liver injury markers and proinflammatory cytokines compared to the unconjugated one which confirmed hepatocytes targeting potential of the synthesized ligand. Asialoglycoprotein receptors targeting could be a landmark strategy for hepatocyte targeting. Thus, the synthesized mannose anchored stearylamine could be a promising novel targeting ligand having hepatocyte targeting potential.
Most encouraging antitubercular activity was noticed for compounds 4u, 4r and 4k with 6.25, 12.5 and 12.5 µG/mL Further, in order to know the binding site interactions, a docking simulations of compounds was performed. These preliminary results will certainly show fruitful directions to improve the activities of compounds.
Background: Dosage forms which precisely control the release rates and targets drugs to a specific body site have made enormous impact in the formulation and development of novel drug delivery systems. Methods: A prolonged release mucoadhesive hydrogel system of nizatidine was prepared by ionotropic gelation and polyelectrolyte complexation technique using natural, biodegradable polymers with or without chitosan. Prepared formulations were subjected to in vitro evaluation and several characterization studies. Results: Formulations with chitosan showed good drug content, swelling index and mucoadhesive strength when compared to batches containing alginate alone. The drug in formulations found to be intact and compatible with polymers used and surface morphology of prepared beads were found satisfactory. Two optimized formulations containing alginatechitosan shows Higuchi model and perfect zero order release. All the formulations with copolymer showed better sustained the drug release when compared with formulations without chitosan. Conclusion: Alginate-chitosan beads prepared by ionotropic geltion and polyelectrolyte complexation method found to be better than ionically cross linked alginate beads alone. Therefore, dual cross-linked beads are promising carrier for oral control release.
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