title: Microencapsulated SLN: An innovative strategy for pulmonary protein delivery.
abstract: 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.
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal; Nanobiofar Group, Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Diana P
authors.initials: DP
authors.lastname: Gaspar
authors.affiliation: Centre for Scientific and Technological Support to Research, University of Vigo, Vigo, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Serra
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Paulo R
authors.initials: PR
authors.lastname: Lino
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Lídia
authors.initials: L
authors.lastname: Gonçalves
authors.affiliation: Colloids and Polymers Physics Group, Condensed Matter Physics Department, Faculty of Physics, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Taboada
authors.affiliation: Nanobiofar Group, Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Remuñán-López
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal. Electronic address: aalmeida@ff.ulisboa.pt.
authors.forename: António J
authors.initials: AJ
authors.lastname: Almeida
mesh_terms: D000327:Adsorption; D002152:Calorimetry, Differential Scanning; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004591:Electrophoresis, Polyacrylamide Gel; D005227:Fatty Acids / Q000737:chemistry; D008055:Lipids / Q000737:chemistry*; D008168:Lung / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D008863:Microspheres; D053758:Nanoparticles; D010206:Papain / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010316:Particle Size; D011208:Powders; D017550:Spectroscopy, Fourier Transform Infrared; D014280:Triglycerides / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D005227:Fatty Acids; D008055:Lipids; D011208:Powders; D014280:Triglycerides; C086409:glyceryl behenate; D010206:Papain; C022618:tristearin
keywords: Adsorption; Microencapsulation; Proteins; Pulmonary administration; Solid lipid nanoparticles; Spray-drying