Solid Lipid Nanoparticles Approach for Lymphatic Targeting Through Intraduodenal Delivery of Quetiapine Fumarate.

BACKGROUND: Lymphatic route is one of the prominent routes for improving the poor bioavailability of the drugs which undergo extensive hepatic first pass metabolism. Nanocarriers (solid lipid nanoparticles) offer a new drug delivery system that could hold great promise for attaining the bioavailability enhancement along with controlled and site specific drug delivery. OBJECTIVE: The aim of the present research work was to prepare and optimized the Quetiapine fumarate (an antipsychotic drug) loaded solid lipid nanoparticles for lymphatic targeting through intraduodenal administration. METHOD: Thirteen quetiapine fumarate loaded solid lipid nanoparticle formulations were developed using different lipids by Microemulsion technique and optimized by box behnken design. RESULTS: Optimized formulation (Q9) had a mean particle size of 230.38 nm with 75.92% of entrapment efficiency. The percentage drug release after 24 h was found to be 95.81%. A significant difference (P<0.05) was found in the in vitro release data of optimized formulation as compared to marketed formulation. In vitro release data of optimized formulation (Q9) was subjected to zero order, first order and Higuchi model to evaluate the release kinetics. Higuchi model was found to be the best fitted model with highest value of correlation coefficient (R2= 0.999). In vivo studies for optimized solid lipid nanoparticles formulation and drug suspension were performed on male Wistar rats after intraduodenal administration and several pharmacokinetic parameters were determined. AUC (0-∞) of optimized formulation was significantly (P<0.01) more than that of drug suspension. Bioavailability of quetiapine in solid lipid nanoparticles was 2.76 fold increased after intraduodenal administration as compared with that of drug suspension. CONCLUSION: On the basis of results of in vitro study, Q9 formulation was selected as optimized formulation. It exhibited better bioavailability as compared to drug suspension. It can be concluded that solid lipid nanoparticles are potential carrier for improving quetiapine bioavailability through lymphatic delivery.

Antimicrobial and cytotoxic activities of turbinariaconoides (j.agardh) kuetz.

Brown alga, Turbinariaconoideswas successively extracted with n-hexane, cyclohexane, methanol and ethanol:water (1:1). The extracts were evaluated for antibacterial and antifungal activities by disc diffusion method. Minimal inhibitory concentration was determined for active extracts by broth dilution method. The antiviral activity and cytotoxicity of the extracts were tested in human embryonic lung (HEL) cells (herpes simplex virus-1, herpes simplex virus-2, vaccinia virus, vesicular stomatitis virus and herpes simplex virus-1 TK- KOS ACVr), human epithelial (HeLa) cells (vesicular stomatitis virus and coxsackie virus B4) and Vero cells (parainfluenza-3 virus, reovirus-1, sindbis virus coxsackie virus B4 and puntatoro virus). The results revealed that extracts exhibited cytotoxicity ranged from 20 to >100 µg/mL. Moderate activity was demonstrated by n-hexane and cyclohexane extracts against viruses, whereas methanol and ethanol:water (1:1) extracts were not active. Ethanol:water (1:1) presented neither antibacterial nor antifungal activity against tested organisms. Cyclohexane extract possessed a broad array of antibacterial activity and exhibited remarkable antifungal property. It is noteworthy that minimal inhibitory concentration of cyclohexane extract against Aspergillusnigeris comparable with that of clotrimazole. This potentiality demonstrates that it could be used to treat bacterial and fungal infections.

Synthesis and pharmacological activities of 2-(3'-substituted-2'-hydroxypropylamino)pyridines.

In the present study, a series of 2-(3'-substituted-2'-hydroxypropylamino)pyridines were synthesized and characterized by IR, 1H-NMR and elemental analysis. The compounds were investigated for anticonvulsant (150, 300 mg/kg) and cardiac activity. 2-(3'-Diethylamino-2'-hydroxypropylamino)pyridine 3 was found to exhibit the highest anticonvulsant activity. 2-(3'-Dimethylamino-2'-hydroxypropylamino)pyridine 2 and 2-[3'-(4''-nitrophenylamino)-2'-hydroxypropylamino]pyridine 6 were found to exhibit negative ionotropic activity. 2-(3'-Dimethylamino-2'-hydroxypropylamino)pyridine 2, 2-[3'-(4''-nitrophenylamino)-2'-hydroxypropylamino]pyridine 6 and 2-(3'-piperidino-2'-hydroxypropylamino)pyridine 8 were found to antagonize exhibit beta-adrenergic activity.