title: Aerosolizable gold nano-in-micro dry powder formulations for theragnosis and lung delivery.
abstract: Functionalized gold nanoparticles (AuNPs) have been widely investigated as promising multifunctional nanosystems for the theragnosis of lung cancer, the most common and prominent cause of cancer death worldwide. Nevertheless, nanoparticles are not in appropriate sizes for an accurate deep lung delivery and the lack of locally and effective delivery of therapeutic biomolecules to the deep lungs is, in fact, the major cause of low therapeutic outcome. Herein we incorporate, for the first time, AuNPs into respirable microparticles. AuNPs were functionalized with biocompatible oligo(2-oxazoline)-based optically stable fluorescent coatings, and conjugated with a laminin peptide (YIGSR) for targeted lung cancer delivery. These POxylated AuNPs were then incorporated into a chitosan matrix by a clean process, supercritical CO2-assisted spray drying (SASD), yielding nano-in-micro clean ultrafine dry powder formulations. The engineered formulations present the adequate morphology and flowability to reach the deep lung, with aerodynamic sizes ranging 3.2-3.8μm, and excellent fine particle fraction (FPF) (FPF of 47% for CHT-bearing targeted AuNPs). The optimal biodegradation and release profiles enabled a sustained and controlled release of the embedded nanoparticles, with enhanced cellular uptake, opening new prospects for future lung theragnosis.
authors.affiliation: LAQV-REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Campus de Caparica, 2829-516 Caparica, Portugal; CICS-UBI, Centro de Investigação em Ciências da Saúde, Universidade da Beira Interior, Avenida Infante D. Henrique, 6200-506 Covilhã, Portugal.
authors.forename: A Sofia
authors.initials: AS
authors.lastname: Silva
authors.affiliation: LAQV-REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Campus de Caparica, 2829-516 Caparica, Portugal.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Sousa
authors.affiliation: LAQV-REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Campus de Caparica, 2829-516 Caparica, Portugal.
authors.forename: Renato P
authors.initials: RP
authors.lastname: Cabral
authors.affiliation: LAQV-REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Campus de Caparica, 2829-516 Caparica, Portugal.
authors.forename: Marta C
authors.initials: MC
authors.lastname: Silva
authors.affiliation: LAQV-REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Campus de Caparica, 2829-516 Caparica, Portugal.
authors.forename: Clarinda
authors.initials: C
authors.lastname: Costa
authors.affiliation: CICS-UBI, Centro de Investigação em Ciências da Saúde, Universidade da Beira Interior, Avenida Infante D. Henrique, 6200-506 Covilhã, Portugal.
authors.forename: Sónia P
authors.initials: SP
authors.lastname: Miguel
authors.affiliation: CQFM and IN, Instituto Superior Técnico, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.
authors.forename: Vasco D B
authors.initials: VDB
authors.lastname: Bonifácio
authors.affiliation: LAQV-REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Campus de Caparica, 2829-516 Caparica, Portugal.
authors.forename: Teresa
authors.initials: T
authors.lastname: Casimiro
authors.affiliation: CICS-UBI, Centro de Investigação em Ciências da Saúde, Universidade da Beira Interior, Avenida Infante D. Henrique, 6200-506 Covilhã, Portugal.
authors.forename: Ilídio J
authors.initials: IJ
authors.lastname: Correia
authors.affiliation: LAQV-REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Campus de Caparica, 2829-516 Caparica, Portugal. Electronic address: air@fct.unl.pt.
authors.forename: Ana
authors.initials: A
authors.lastname: Aguiar-Ricardo
mesh_terms: D000072283:A549 Cells; D000336:Aerosols / Q000008:administration & dosage* / Q000737:chemistry*; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D048271:Chitosan / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods; D058995:Dry Powder Inhalers / Q000379:methods; D005079:Excipients / Q000737:chemistry; D006046:Gold / Q000737:chemistry*; D006801:Humans; D008168:Lung / Q000378:metabolism*; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D011208:Powders / Q000008:administration & dosage* / Q000737:chemistry*
chemical_list: D000336:Aerosols; D004337:Drug Carriers; D005079:Excipients; D011208:Powders; D006046:Gold; D048271:Chitosan
keywords: Dry powder formulation; Gold nanoparticles; Lung cancer; Nano-in-micro; Pulmonary delivery; Spray drying; Supercritical CO(2)