Microencapsulated SLN: An innovative strategy for pulmonary protein delivery.

Associating protein with nanoparticles is an interesting strategy to improve their bioavailability and biological activity. Solid lipid nanoparticles (SLN) have been sought as carriers for therapeutic proteins transport to the lung epithelium. Nevertheless, because of their low inertia, nanoparticles intended for pulmonary application usually escape from lung deposition. To overcome this problem, the production of spray-dried powders containing nanoparticles has been recently reported. Herein we developed new hybrid microencapsulated SLN for pulmonary administration, containing a model protein (papain, PAP). PAP was adsorbed onto glyceryl dibehenate and glyceryl tristearate SLN. Physical characterization using transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) confirmed the interaction between PAP and SLN corroborating that the protein was efficiently adsorbed at SLN's surface. PAP adsorption onto SLN (PAP-SLN) slightly increased particle size, while decreasing the SLN negative surface charge. The adsorption process followed a Freundlich type of adsorption isotherm. Nanoformulations were then spray-dried, originating spherical microparticles with suitable aerodynamic characteristics. Full characterization of microparticles was performed using scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and isothermal titration calorimetry (ITC). PAP was released from dry powders in a higher extent when compared with non spray-dried SLN. Nevertheless, protein stability was kept throughout microsphere production, as assessed by SDS-PAGE.