Aerosolizable gold nano-in-micro dry powder formulations for theragnosis and lung delivery

A. Sofia Silva, Ana M. Sousa, Renato P. Cabral, Marta C. Silva, Clarinda Costa, Sónia P. Miguel, Vasco D.B. Bonifácio, Teresa Casimiro, Ilídio J. Correia, Ana Aguiar-Ricardo

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

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 3.2–3.8 μm, 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.

Original languageEnglish
Pages (from-to)240-249
Number of pages10
JournalInternational Journal of Pharmaceutics
Volume519
Issue number1-2
DOIs
Publication statusPublished - 15 Mar 2017

Keywords

  • Dry powder formulation
  • Gold nanoparticles
  • Lung cancer
  • Nano-in-micro
  • Pulmonary delivery
  • Spray drying
  • Supercritical CO

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