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Development of Novel Octanoyl Chitosan Nanoparticles for Improved Rifampicin Pulmonary Delivery: Optimization by Factorial Design
Authors
A Elhissi
A Grenha
+58 more
A Grenha
A Kroll
AA Ishikawaa
AH Kendrick
AP Ranjan
BR Conway
C Hoskins
C Parlati
C Singh
D Klariæ
DJ Kirby
E Seydoux
G Ma
H Jeffery
H Lv
H Murakami
HM Mansour
I Aranaz
I. Saleem
IMV Lubben
J Liu
J Zhang
JY Menon
Kailash C. Petkar
Kevin M. G. Taylor
Krutika K. Sawant
L Hu
M Amidi
M González-Juarrero
M Holzer
M Motiei
M Tatarczak
MD Bhavsar
ML Manca
MRC Marques
N. Kunda
NA Efiana
P Costa
PC Li HY Seville
PP Shah
R Alex
R Pandey
S Bolton
S. Somavarapu
SA Benetton
SA Moschos
Sandip Chavhan
T Rawal
TVP Doan
TW Atkins
U Bilati
VK Mourya
Y Cho
Y Cho
Y Huang
Y Li
YY Yang
Z Zong
Publication date
30 April 2018
Publisher
'American Association of Pharmaceutical Scientists (AAPS)'
Doi
Cite
Abstract
A novel hydrophobic chitosan derivative, octanoyl chitosan (OC) with improved organic solubility was synthesized, characterized, and employed for the preparation of rifampicin (Rif) encapsulated nanoparticle formulations for pulmonary delivery. OC was characterized to confirm acyl group substitution and cytotoxicity in A549 epithelial lung cells. OC nanoparticles were produced by the double emulsion solvent evaporation technique without cross-linking and characterized for particle size distribution, morphology, crystallinity, thermal stability, aerosol delivery, and drug release rate. OC was successfully synthesized with substitution degree of 44.05 ± 1.75%, and solubility in a range of organic solvents. Preliminary cytotoxicity studies of OC showed no effect on cell viability over a period of 24 h on A549 cell lines. OC nanoparticles were optimized using a 32full factorial design. An optimized batch of OC nanoparticles, smooth and spherical in morphology, had mean hydrodynamic diameter of 253 ± 19.06 nm (PDI 0.323 ± 0.059) and entrapment efficiency of 64.86 ± 7.73% for rifampicin. Pulmonary deposition studies in a two-stage impinger following aerosolization of nanoparticles from a jet nebulizer gave a fine particle fraction of 43.27 ± 4.24%. In vitro release studies indicated sustained release (73.14 ± 3.17%) of rifampicin from OC nanoparticles over 72 h, with particles demonstrating physical stability over 2 months. In summary, the results confirmed the suitability of the developed systems for pulmonary delivery of drugs with excellent aerosolization properties and sustained-release characteristics. © 2018, American Association of Pharmaceutical Scientists
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UCL Discovery
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oai:eprints.ucl.ac.uk.OAI2:100...
Last time updated on 27/02/2018
Crossref
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info:doi/10.1208%2Fs12249-018-...
Last time updated on 02/01/2020
LJMU Research Online (Liverpool John Moores University)
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Last time updated on 21/11/2018