Design of lipid nanoparticles for the oral delivery of hydrophilic macromolecules

Abstract

Colloidal drug carriers prepared from solid triglycerides have been presented as a promising alternative to polymer nanoparticles. The present work is aimed at developing surface-modified lipid nanoparticles intended to encapsulate peptides within their structure and to study their physicochemical properties and in vitro stability in gastrointestinal fluids. The final goal is to explore their potential as oral delivery vehicles for macromolecules. The W/O/W multiple emulsion technique was originally applied and conveniently modified for the production of tripalmitin nanoparticles. This technique was selected because its makes the encapsulation of peptides feasible. Additionally, the surface of the particles could be modified through the incorporation of Poloxamer 188 or the lipid derivative PEG 2000-stearate into the formulation. This modification led to a reduction in the zeta potential values, varying from −34 mV for the non-coated particles to −20 mV for those prepared with PEG-stearate. Results of the stability of the nanoparticles in gastric and intestinal media indicate that the low pH of the gastric medium and the pancreatic enzymes in intestinal medium are responsible for the extensive aggregation and degradation of the non-coated lipid nanoparticles (80% degradation in 4 h). In contrast, PEG-stearate coated nanoparticles were more stable, as their polymer coating layer totally prevented aggregation in both media and significantly reduced pancreatin-induced degradation (40% approximately in 4 h). Preliminary studies showed that insulin, chosen as a model peptide, could be associated and released from PEG-stearate coated nanoparticles. Nevertheless, further work is required in order to optimize the release behavior of the entrapped peptide.