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Alimentary proteins can be viewed as an adequate material for the preparation of nanoparticles and microparticles. They offer several advantages such as their digestibility, price and a good capability to interact with a wide variety of compounds and nutrients. The aim of this work was to prepare and characterize casein nanoparticles for the oral delivery of folic acid. These nanoparticles were prepared by a coacervation process, stabilized with either lysine or arginine and, finally, dried by spray-drying. For some batches, the effect of a supplementary treatment of nanoparticles (before drying) with hydrodynamic high pressure on the properties of the resulting carriers was also evaluated. The resulting nanoparticles displayed a mean size close to 150 nm and a folic acid content of around 25 mg per mg nanoparticle. From the in vitro release studies, it was observed that casein nanoparticles acted as gastro-resistant devices and, thus, folic acid was only released under simulated intestinal conditions. For the pharmacokinetic study, folic acid was orally administered to laboratory animals as a single dose of 1 mg/kg. Animals treated with folic acidloaded casein nanoparticles displayed significantly higher serum levels than those observed in animals receiving an aqueous solution of the vitamin. As a consequence the oral bioavailability of folic acid when administered in casein nanoparticles was calculated to be around 52%, a 50% higher than with the traditional aqueous solution. Unfortunately, the treatment of casein nanoparticles by hydrodynamic high pressure modified neither the release profile of the vitamin nor its oral bioavailability.

The aim of this work was to study the potential of pegylated poly(anhydride) nanoparticles as carriers for the oral delivery of paclitaxel (PTX). Paclitaxel is an anticancer drug, ascribed to the class IV of the Biopharmaceutical Classification system, characterised for its low aqueous solubility and to act as a substrate of the P-glycoprotein and cytochrome P450. For the pegylation of nanoparticles, three different poly(ethylene glycol) (PEG) were used: PEG 2000 (PTX-NP2), PEG 6000 (PTX-NP6) and PEG 10000 (PTX-NP10). The transport and permeability of paclitaxel through the jejunum mucosa of rats was determined in Ussing chambers whereas its oral bioavailability was studied in rats. The loading of PTX in pegylated nanoparticles increased between 3 and 7-times the intestinal permeability of paclitaxel through the jejunum compared with the commercial formulation Taxol®. Interestingly, the permeability of PTX was significantly higher for PTX-NP2 and PTX-NP6 than for PTX-NP10. In the in vivo studies similar results were obtained. When PTX-NP2 and PTX-NP6 were administered to rats by the oral route, sustained and therapeutic plasma levels of paclitaxel for at least 48-h were observed. The relative oral bioavailability of paclitaxel delivered in nanoparticles was calculated to be 70% for PTX-NP2, 40% for PTX-NP6 and 16% in case of PTX-NP10. All of these observations would be related with both the bioadhesive properties of these carriers and the inhibitory effect of PEG on the activity of both P-gp and P450 cytochrome.

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