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 D. A., George, Graeme, Beagley, Kenneth, Ferro, Vito, Wang, Hui and 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: 1455-1466. doi:10.1021/acs.molpharmaceut.5b00859


Author Muhsin, Mohammad D. A.
George, Graeme
Beagley, Kenneth
Ferro, Vito
Wang, Hui
Islam, Nazrul
Title Effects of chemical conjugation of L‑leucine to chitosan on dispersibility and controlled release of drug from a nanoparticulate dry powder inhaler formulation
Journal name Molecular Pharmaceutics   Check publisher's open access policy
ISSN 1543-8384
1543-8392
Publication date 2016-05-02
Sub-type Article (original research)
DOI 10.1021/acs.molpharmaceut.5b00859
Open Access Status Not Open Access
Volume 13
Issue 5
Start page 1455
End page 1466
Total pages 12
Place of publication Washington, DC, United States
Publisher American Chemical Society
Language eng
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.
Keyword Nanoparticles
Dry powder inhaler (DPI)
Pulmonary delivery
Controlled release
Chitosan
L-leucine
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Chemistry and Molecular Biosciences
 
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Created: Sat, 21 May 2016, 01:30:14 EST by Associate Professor Vito Ferro on behalf of School of Chemistry & Molecular Biosciences