title: Development of an inhalable, stimuli-responsive particulate system for delivery to deep lung tissue.
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.
authors.affiliation: Department of Chemistry, School of Sciences & Engineering, The American University in Cairo, Cairo, Egypt.
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Abbas
authors.affiliation: Department of Chemistry, School of Sciences & Engineering, The American University in Cairo, Cairo, Egypt. Electronic address: hazzazy@aucegypt.edu.
authors.forename: Hassan M E
authors.initials: HM
authors.lastname: Azzazy
authors.affiliation: 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.
authors.forename: Salma
authors.initials: S
authors.lastname: Tammam
authors.affiliation: Laboratory of Pharmaceutical Technology and Biopharmaceutics, University of Bonn, Bonn, Germany; Laboratory of Pharmaceutical Engineering, University of Franche-Comté, Besançon, France.
authors.forename: Alf
authors.initials: A
authors.lastname: Lamprecht
authors.affiliation: Laboratory of Pharmaceutical Technology and Biopharmaceutics, University of Bonn, Bonn, Germany; Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut, Egypt.
authors.forename: Mohamed Ehab
authors.initials: ME
authors.lastname: Ali
authors.affiliation: Department of Chemistry, Institute of Physical Chemistry, University of Cologne, Cologne, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Schmidt
authors.affiliation: Department of Chemistry, Institute of Physical Chemistry, University of Cologne, Cologne, Germany.
authors.forename: Silvio
authors.initials: S
authors.lastname: Sollazzo
authors.affiliation: Department of Chemistry, Institute of Inorganic Chemistry, University of Cologne, Cologne, Germany.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Mathur
mesh_terms: D000280:Administration, Inhalation; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000008:administration & dosage / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005612:Freeze Drying; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008280:Magnetics; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D011208:Powders / Q000008:administration & dosage* / Q000737:chemistry; D014407:Tumor Cells, Cultured
chemical_list: D004337:Drug Carriers; D011208:Powders; D048271:Chitosan
keywords: Cancer; Chitosan; Deep lung tissue; Drug targeting; Magnetic nanoparticles; Next generation impactor; Stimuli-responsive