Nano-in-Micro POxylated Polyurea Dendrimers and Chitosan Dry Powder Formulations for Pulmonary Delivery

Rita B. Restani, A. Sofia Silva, Rita F. Pires, Renato Cabral, Ilídio J. Correia, Teresa Casimiro, Vasco D B Bonifácio, Ana Aguiar-Ricardo

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18 Citations (Scopus)

Abstract

Pulmonary administration offers excellent advantages over conventional drug delivery routes, including increasing therapeutics bioavailability, and avoiding long-term safety issues. Formulations of nano-in-micro dry powders for lung delivery are engineered using (S)-ibuprofen as a model drug. These biodegradable formulations comprise nanoparticles of drug-loaded POxylated polyurea dendrimers coated with chitosan using supercritical-fluid-assisted spray drying. The formulations are characterized in terms of morphology, particle-size distribution, in vitro aerodynamic particle pulmonary distribution, and glutathione-S-transferase assay. It is demonstrated that ibuprofen-loaded nanoparticles can be successfully incorporated into microspheres with adequate aerodynamic properties, mass median aerodynamic diameter (1.86-3.83 μm), and fine particle fraction (28%-45%), for deposition into the deep lung. The (S)-ibuprofen dry powder formulations show enhanced solubility, high swelling behavior and a sustained drug release at physiologic pH. Also, POxylated polyureas decrease the (S)-ibuprofen toxic effect on cancer cellular growth. The 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assays show no significant cytotoxicity on the metabolic activity of human lung adenocarcinoma ephithelial (A549) cell line for the lowest concentration (1 × 10-3 m), even for longer periods of contact with the cells (up to 120 h), and in the normal human dermal fibroblasts cell line the toxic effect is also reduced.

Original languageEnglish
Pages (from-to)851-858
Number of pages8
JournalParticle and Particle Systems Characterization
Volume33
Issue number11
DOIs
Publication statusPublished - 1 Nov 2016

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Keywords

  • Dry powder formulations
  • Polyurea dendrimers
  • Pulmonary delivery
  • Spray drying
  • Supercritical carbon dioxide

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