Enhanced oral bioavailability of nevirapine within micellar nanocarriers compared with Viramune(®).

In this work, Nevirapine (NVP) was encapsulated within three derivatives of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) block copolymers (Tetronic(®) 904, 1107 and Pluronic(®) F127) with and without the addition of three pharmaceutical cosolvents (glycerin, propylene glycol and polyethylene glycol 400) over a wider range of concentrations (0-40% v/v). Also, we evaluated the effect of addition of the cosolvents on the micellar size as determined by dynamic light scattering (DLS) measurements and transmission electron microscopy (TEM). The solubilization capacity of the systems was investigated by UV-spectrophotometry (282nm) and the systems stability was evaluated for 1 month at 25°C. Finally, oral bioavailability of the NVP-loaded micellar systems (2mg/mL) was assessed in male Wistar rats (8mg/kg) and compared with a pediatric commercially available formulation (Viramune(®)). The present study demonstrates that PEO-PPO-PEO polymeric micelles were able to enhance apparent aqueous solubility of NVP with the addition of cosolvents. Moreover, micellar nanocarriers significantly (p<0.05) improved the oral bioavailability of the drug versus Viramune(®). Overall results support the suitability of the strategy toward the development of an optimized NVP aqueous formulation to prevent HIV/AIDS mother-to-child transmission.

Paclitaxel-loaded PCL-TPGS nanoparticles: in vitro and in vivo performance compared with Abraxane®.

The purpose of this work was to develop Cremophor(®) EL-free nanoparticles (NPs) loaded with Paclitaxel (PTX) in order to improve the drug i.v. pharmacokinetic profile and to evaluate its activity against commercially available formulations such as Taxol(®) and Abraxane(®). PTX-loaded poly(ε-caprolactone)-alpha tocopheryl polyethylene glycol 1000 succinate (PCL-TPGS) NPs were prepared using three different techniques: (i) by nanoprecipitation (NPr-method), (ii) by emulsion-solvent evaporation homogenized with an Ultra-Turrax(®) (UT-method) and (iii) by emulsion-solvent evaporation homogenized with an ultrasonicator (US-method). The NPs prepared by US-method showed the smallest size and the highest drug content. The NPs exhibited a slow and continuous release of PTX. The in vitro anti-tumoral activity was assessed using two human breast cancer cell lines (MCF-7 and MDA-MB-231) with the WTS assay. Cytotoxicity studies with both cell lines showed that PTX-loaded PCL-TPGS NPs exhibited better anti-cancer activity compared to PTX solution and the commercial formulation Abraxane(®) at different concentrations. Importantly, in the case of triple negative MDA-MB-231 breast cancer cells, the IC50 value for PTX-loaded PCL-TPGS NPs was 7.8 times lower than Abraxane(®). Finally, in vivo studies demonstrated that PTX-loaded PCL-TPGS NPs exhibited longer systemic circulation time and slower plasma elimination rate than Taxol(®) and Abraxane(®). Therefore, the novel NPs investigated might be an alternative nanotechnological platform for PTX delivery system in cancer chemotherapy.