Development of an inhalable, stimuli-responsive particulate system for delivery to deep lung tissue

Yasmine Abbas; Hassan M E Azzazy; Salma Tammam; Alf Lamprecht; Mohamed Ehab Ali; Annette Schmidt; Silvio Sollazzo; Sanjay Mathur

doi:10.1016/j.colsurfb.2016.05.031

Development of an inhalable, stimuli-responsive particulate system for delivery to deep lung tissue

Colloids Surf B Biointerfaces. 2016 Oct 1:146:19-30. doi: 10.1016/j.colsurfb.2016.05.031. Epub 2016 May 12.

Authors

Yasmine Abbas¹, Hassan M E Azzazy², Salma Tammam³, Alf Lamprecht⁴, Mohamed Ehab Ali⁵, Annette Schmidt⁶, Silvio Sollazzo⁶, Sanjay Mathur⁷

Affiliations

¹ Department of Chemistry, School of Sciences & Engineering, The American University in Cairo, Cairo, Egypt.
² Department of Chemistry, School of Sciences & Engineering, The American University in Cairo, Cairo, Egypt. Electronic address: hazzazy@aucegypt.edu.
³ Department of Chemistry, School of Sciences & Engineering, The American University in Cairo, Cairo, Egypt; Laboratory of Pharmaceutical Technology and Biopharmaceutics, University of Bonn, Bonn, Germany.
⁴ Laboratory of Pharmaceutical Technology and Biopharmaceutics, University of Bonn, Bonn, Germany; Laboratory of Pharmaceutical Engineering, University of Franche-Comté, Besançon, France.
⁵ Laboratory of Pharmaceutical Technology and Biopharmaceutics, University of Bonn, Bonn, Germany; Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut, Egypt.
⁶ Department of Chemistry, Institute of Physical Chemistry, University of Cologne, Cologne, Germany.
⁷ Department of Chemistry, Institute of Inorganic Chemistry, University of Cologne, Cologne, Germany.

PMID: 27244047
DOI: 10.1016/j.colsurfb.2016.05.031

Abstract

Lung cancer, the deadliest solid tumor among all types of cancer, remains difficult to treat. This is a result of unavoidable exposure to carcinogens, poor diagnosis, the lack of targeted drug delivery platforms and limitations associated with delivery of drug to deep lung tissues. Development of a non-invasive, patient-convenient formula for the targeted delivery of chemotherapeutics to cancer in deep lung tissue is the aim of this study. The formulation consisted of inhalable polyvinylpyrrolidone (PVP)/maltodextrin (MD)-based microparticles (MPs) encapsulating chitosan (CS) nanoparticles (NPs) loaded with either drug only or drug and magnetic nanoparticles (MNPs). Drug release from CS NPs was enhanced with the aid of MNPs by a factor of 1.7 in response to external magnetic field. Preferential toxicity by CS NPs was shown towards tumor cells (A549) in comparison to cultured fibroblasts (L929). The prepared spray freeze dried (SFD) powders for CS NPs and CS MNPs were of the same size at ∼6μm. They had a fine particle fraction (FPF≤5.2μm) of 40-42% w/w and mass median aerodynamic diameter (MMAD) of 5-6μm as determined by the Next Generation Impactor (NGI). SFD-MPs of CS MNPs possess higher MMAD due to the high density associated with encapsulated MNPs. The developed formulation demonstrates several capabilities including tissue targeting, controlled drug release, and the possible imaging and diagnostic values (due to its MNPs content) and therefore represents an improved therapeutic platform for drug delivery to cancer in deep lung tissue.

Keywords: Cancer; Chitosan; Deep lung tissue; Drug targeting; Magnetic nanoparticles; Next generation impactor; Stimuli-responsive.

MeSH terms

Administration, Inhalation
Chemistry, Pharmaceutical
Chitosan / administration & dosage
Chitosan / chemistry*
Drug Carriers / chemistry
Drug Delivery Systems*
Drug Liberation
Freeze Drying
Humans
Lung / drug effects*
Lung / metabolism
Lung Neoplasms / drug therapy*
Lung Neoplasms / metabolism
Magnetics
Nanoparticles / administration & dosage
Nanoparticles / chemistry*
Particle Size
Powders / administration & dosage*
Powders / chemistry
Tumor Cells, Cultured

Substances

Drug Carriers
Powders
Chitosan