Background and the aim of the study: The objective of the present study was to formulate and optimize nanoparticles (NPs) of sildenafil-loaded poly (lactic-co-glycolic acid) (PLGA) by double emulsion solvent evaporation (DESE) method. The relationship between design factors and experimental data was evaluated using response surface methodology. Method: A Box-Behnken design was made considering the mass ratio of drug to polymer (D/P), the volumetric proportion of the water to oil phase (W/O) and the concentration of polyvinyl alcohol (PVA) as the independent agents. PLGA-NPs were successfully prepared and the size (nm), entrapment efficiency (EE), drug loading (DL) and cumulative release of drug from NPs post 1 and 8 hrs were assessed as the responses. Results: The NPs were prepared in a spherical shape and the sizes range of 240 to 316 nm. The polydispersity index of size was lower than 0.5 and the EE (%) and DL (%) varied between 14-62% and 2-6%, respectively. The optimized formulation with a desirability factor of 0.9 was selected and characterized. This formulation demonstrated the particle size of 270 nm, EE of 55%, DL of 3.9% and cumulative drug release of 79% after 12 hrs. In vitro release studies showed a burst release at the initial stage followed by a sustained release of sildenafil from NPs up to 12 hrs. The release kinetic of the optimized formulation was fitted to Higuchi model. Conclusions: Sildenafil citrate NPs with small particle size, lipophilic feature, high entrapment efficiency and good loading capacity is produced by this method. Characterization of optimum formulation, provided by an evaluation of experimental data, showed no significant difference between calculated and measured data.

Background: Curcumin, a bioactive component with multiple characteristics, has been shown to have many therapeutic effects. However, there are several limitations regarding the use of curcumin such as instability, low solubility, poor bioavailability, and rapid elimination. Different approaches have been used to solve these problems. Materials and methods: In this study, surface-modified nanosuspension (NS) is investigated as a novel brain delivery system. Two different methods were used for the preparation of nanosuspensions with two different stabilizers. The surface of the nanosuspensions was coated with D-α-tocopheryl polyethylene glycol 1,000 succinate (TPGS) and Tween 80 using physical adsorption. Curcumin NSs were prepared using two different top-down techniques by high-pressure homogenizer and probe sonicator. A validated sensitive and selective high-performance liquid chromatography method using fluorescence detection was used for the determination and quantification of curcumin. Pharmacokinetics and biodistribution of curcumin NSs and solutions after intravenous administration in rats were studied. Results: Higher levels of curcumin in the brain were detected when Tween 80-coated NS was used compared with the curcumin solution and TPGS coated NS (TPGS-NS) (P-value<0.05). Absorption of ApoE and/or B by Tween 80-coated nanoparticles (NPs) from the blood were caused transferring of these NPs into the brain using receptor-mediated endocytosis. Distribution of TPGS-NS in the brain compared with the curcumin solution was higher (P-value<0.05). Higher levels of curcumin concentration in the liver, spleen, and lung were also observed with TPGS-NS. Conclusion: The results of this study indicate that the surface-coating of NSs by Tween 80 may be used to improve the biodistribution of curcumin in the brain.