title: Effects of Chemical Conjugation of l-Leucine to Chitosan on Dispersibility and Controlled Release of Drug from a Nanoparticulate Dry Powder Inhaler Formulation.
abstract: This study investigated l-leucine-conjugated chitosan as a drug delivery vehicle in terms of dispersibility and controlled release from a nanoparticulate dry powder inhaler (DPI) formulation for pulmonary delivery using diltiazem hydrochloride (DH) as the model drug. DH-loaded nanoparticles of chitosan and conjugate were prepared by water-in-oil emulsification followed by glutaraldehyde cross-linking. Nanoparticles were characterized by dynamic light scattering for particle size, X-ray photoelectron spectroscopy for surface composition, and twin stage impinger for drug dispersibility. The controlled release of DH was studied in phosphate-buffered saline (pH 7.3 ± 0.2, 37 °C) using UV spectrophotometry. The fine particle fractions of conjugated chitosan with and without drug were higher than those of nonconjugated chitosan nanoparticles. The conjugate nanoparticles were superior to those of unmodified chitosan in drug loading, entrapment efficiency, and controlled release profile. The higher dispersibility was attributed to the amphiphilic environment of the l-leucine conjugate and hydrophobic cross-links, and the release profile reflects the greater swelling. The conjugated chitosan nanoparticles could be useful, after appropriate testing for biodegradability and toxicity, as an alternative carrier for lung drug delivery with enhanced aerosolization and prolonged drug release from nanoparticulate DPI formulations.
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology , 60 Musk Avenue, Kelvin Grove, Brisbane, Queensland 4059, Australia.|Pharmacy Discipline, Faculty of Health, Queensland University of Technology , Brisbane, Queensland 4000, Australia.
authors.forename: Mohammad D A
authors.initials: MD
authors.lastname: Muhsin
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology , 60 Musk Avenue, Kelvin Grove, Brisbane, Queensland 4059, Australia.|School of Chemistry, Physics and Mechanical Engineering, Faculty of Science and Engineering, Queensland University of Technology , Brisbane, Queensland 4000, Australia.
authors.forename: Graeme
authors.initials: G
authors.lastname: George
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology , 60 Musk Avenue, Kelvin Grove, Brisbane, Queensland 4059, Australia.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Beagley
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland , Brisbane, Queensland 4072, Australia.
authors.forename: Vito
authors.initials: V
authors.lastname: Ferro
authors.affiliation: Pharmacy Discipline, Faculty of Health, Queensland University of Technology , Brisbane, Queensland 4000, Australia.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology , 60 Musk Avenue, Kelvin Grove, Brisbane, Queensland 4059, Australia.|Pharmacy Discipline, Faculty of Health, Queensland University of Technology , Brisbane, Queensland 4000, Australia.
authors.forename: Nazrul
authors.initials: N
authors.lastname: Islam
mesh_terms: D000280:Administration, Inhalation; D002626:Chemistry, Pharmaceutical / Q000379:methods; D048271:Chitosan / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D065546:Drug Liberation / Q000502:physiology; D058995:Dry Powder Inhalers / Q000379:methods; D005079:Excipients / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D007930:Leucine / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D056951:Photoelectron Spectroscopy / Q000379:methods
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005079:Excipients; D048271:Chitosan; D007930:Leucine
keywords: chitosan; controlled release; diltiazem hydrochloride; dry powder inhaler (DPI); l-leucine; nanoparticles; pulmonary delivery