Insulin-Loaded PLGA Nanoparticles for Oral Administration: An In Vitro Physico-Chemical Characterization

The aim of this work was to study poly(d,l-lactic-co-glycolic) acid (PLGA) nanoparticles - formulated by a modified solvent diffusion technique - applied as model nanocarriers for insulin in potential oral administrations. These nanostructures consisted of a blend matrix formed by PLGA copolymer and polyoxyethylene derivatives. Two types of blend formulations, PLGA:poloxamer (Pluronic F68 (R)) and PLGA:poloxamine (Tetronic T904 (R)), were analyzed, and the results compared to those obtained with pure PLGA nanoparticles. The work has been divided into two parts. (a) Firstly, the stability of the unloaded nanoparticles in simulated gastric and intestinal fluids was studied. Degradation studies reflected a strong interaction between the pure PLGA nanoparticles and the digestive enzymes. However, this interaction was considerably reduced in the blend formulations, although the PLGA:poloxamine system became colloidally unstable in the simulated gastric fluid. (b) Secondly, the effect of the net charge of the encapsulated macromolecule in the final properties of the blend formulations was studied by encapsulating insulin below and above its corresponding iso-electric point. The net charge of the encapsulated protein showed a clear effect in the final size of the nanoparticles, while the encapsulation efficiency was controlled by the polyoxyethylene derivative presents in the blend formulation. The obtained results show that those carriers formed with encapsulated insulin in PLGA-Pluronic F68 (R) particles are capable, at least in vitro, to overcome the gastrointestinal barrier. Therefore, these nanocarriers seem to be appropriate for oral administration of insulin, although performing in vivo studies becomes necessary to corroborate such statement.