Gliadin nanoparticles for the controlled release of all-trans-retinoic acid

The general objective of this work was to study the feasibility of preparing small-sized carriers from vegetal macromolecules. For this purpose, gliadin (a vegetal protein fraction from wheat gluten) nanoparticles were chosen as drug carriers for all-trans-retinoic acid (RA). The systems were prepared by a desolvation method for macromolecules, which enabled us to obtain gliadin nanoparticles of about 500 nm, with a yield close to 90% of the initial protein. All experiments were performed using environmentally acceptable solvents such as ethanol and water. Moreover, due to the low solubility of this protein in water and to its high hydrophobicity, nanoparticles from gliadin do not need any further chemical or physical treatment to harden them. Gliadin nanoparticles were quite stable over 4 days in phosphate-buffered saline (PBS), but were degraded rapidly over 3 h when incubated in PBS solution containing trypsin. However, chemical cross-linkage of nanoparticles with glutaraldehyde significantly increased their stability: Under our experimental conditions, the payload limit was 76.4 mu g RA/mg nanoparticles (for an RA/initial protein ratio of 90 mu g/mg), which corresponded to a RA entrapment efficiency of about 75% of added drug. Nevertheless, the entrapment efficiency was high (between 97 and 85%) for RA/initial protein ratios up to 90 mu g/mg. Finally, the in vitro release profiles of RA-loaded gliadin nanoparticles showed a biphasic pattern. An initial burst effect (in which about 20% RA was released) followed by zero-order diffusion (release rate 0.065 mg RA/h) were observed.