Gliadin characterization by SANS and gliadin nanoparticle growth modelization.

Nanosized colloidal carriers can ensure a controlled and targeted therapeutic substances delivery. The original contribution of this work was to use biopolymers of vegetable source, which are an interesting alternative to synthetic polymers. The aim of this study was to prepare submicronic particles from wheat proteins: Gliadins extracted from gluten. The carrier preparation was based on the desolvatation of the macromolecules by a couple solvent/non-solvent of the proteins. In a first step, it was of interest to elucidate the gliadin macromolecular conformation in order to understand the mechanism of nanoparticle formation. The experimental work was based on SANS experiments. Because the size of the colloidal particle suspension is an important parameter to monitor, the modelization of the particle growth was thoroughly studied. Furthermore, it was observed that the determination of the solubility parameters of the proteins allowed optimization of the size of the particles. From those previous experimental results it can be concluded that there is a correlation between the protein conformation in the solvent and the size of the nanoparticles (NP).

Microspheres based on inulin for the controlled release of serine protease inhibitors: preparation, characterization and in vitro release.

The pharmacological activity of serine protease inhibitors, potential drugs for the treatment of thrombosis, is often linked to the presence of amidine functions. With the aim of developing a suitable formulation for these compounds, inulin and inulin acetate associated or not with 1,12-dodecanedicarboxylic acid, were chosen to prepare microspheres. Using a coacervation method, these biocompatible polymers led to microspheres of about 0.5-5 microm. The encapsulation of a water-soluble model drug (E,E)-bis(amidinobenzylidene)cycloheptanone [(E,E)-BABCH] in these microspheres was studied. In this investigation, factorial designs were used to determine the joint influence of several variables (drug mass, speed and time of formulation stirring, centrifugation time) for an optimum encapsulation efficiency. Results revealed that encapsulation efficiency reached 65% whatever the nature of the biopolymer, by using a stirring time of 30 min, a high stirring speed and a centrifugation time of 15 min. (E,E)-BABCH release from microspheres was examined in an in vitro model. The profiles were characterized by three phases strongly dependent on the microspheres and the diacid association displayed a crucial role. With inulin and inulin acetate, the initial phase was a rapid 'drug burst'. Within the first 5 min, 58-62% of the drug were delivered. Microspheres of inulin acetate associated with 1,12-dodecanedicarboxylic acid, showed a slower release with only 32% of the drug delivered after 15 min. After a slow diffusion phase (33 h), an increasing rate until complete drug release was observed for 2.5 days.