Effects of chemical conjugation of L-leucine to chitosan on dispersibility and controlled release of drug from a nanoparticulate dry powder inhaler formulation

Muhsin, Mohammad, George, Graeme, Beagley, Kenneth, Ferro, Vito, Wang, Hui, & Islam, Nazrul (2016) Effects of chemical conjugation of L-leucine to chitosan on dispersibility and controlled release of drug from a nanoparticulate dry powder inhaler formulation. Molecular Pharmaceutics, 13(5), pp. 1455-1466.

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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 crosslinking. Nanoparticles were characterised by dynamic light scattering (DLS) for particle size, X-ray Photoelectron Spectroscopy (XPS) for surface composition, and by Twin Stage Impinger (TSI) for drug dispersibility. The controlled release of DH was studied in phosphate buffered saline (PBS, pH 7.3±0.2, 37 °C) using UV spectrophotometry. The fine particle fractions (FPFs) of conjugated chitosan with and without drug were higher than those of non-conjugated 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 crosslinks 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.

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3 citations in Scopus
2 citations in Web of Science®
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ID Code: 95350
Item Type: Journal Article
Refereed: Yes
Keywords: nanoparticles, dry powder inhaler, pulmonary drug delivery, controlled release,, chitosan, L-leucine, diltiazem hydrochloride
DOI: 10.1021/acs.molpharmaceut.5b00859
ISSN: 1543-8392
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > PHARMACOLOGY AND PHARMACEUTICAL SCIENCES (111500) > Pharmaceutical Sciences (111504)
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Current > QUT Faculties and Divisions > Science & Engineering Faculty
Copyright Owner: Copyright 2016 American Chemical Society
Deposited On: 29 Jun 2016 03:45
Last Modified: 27 Jun 2017 18:01

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