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Chitosan-modified dry powder formulations for pulmonary gene delivery

Li, H.-Y. and Birchall, James Caradoc 2006. Chitosan-modified dry powder formulations for pulmonary gene delivery. Pharmaceutical Research 23 (5) , pp. 941-950. 10.1007/s11095-006-0027-x

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Abstract

Purpose Spray-drying is an effective process for preparing micron-dimensioned particles for pulmonary delivery. Previously, we have demonstrated enhanced dispersibility and fine particle fraction of spray-dried nonviral gene delivery formulations using amino acids or absorption enhancers as dispersibility-enhancing excipients. In this study, we investigate the use of the cationic polymer chitosan as a readily available and biocompatible dispersibility enhancer. Methods Lactose-lipid:polycation:pDNA (LPD) powders were prepared by spray-drying and post-mixed with chitosan or spray-dried chitosan. In addition, the water-soluble chitosan derivative, trimethyl chitosan, was added to the lactose-LPD formulation before spray-drying. Results Spray-dried chitosan particles, displaying an irregular surface morphology and diameter of less than 2 μm, readily adsorbed to lactose-LPD particles following mixing. In contrast with the smooth spherical surface of lactose-LPD particles, spray-dried trimethyl chitosan-lactose-LPD particles demonstrated increased surface roughness and a unimodal particle size distribution (mean diameter 3.4 μm), compared with the multimodal distribution for unmodified lactose-LPD powders (mean diameter 23.7 μm). The emitted dose and in vitro deposition of chitosan-modified powders was significantly greater than that of unmodified powders. Moreover, the inclusion of chitosan mediated an enhanced level of reporter gene expression. Conclusions In summary, chitosan enhances the dispersibility and in vitro pulmonary deposition performance of spray-dried powders.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Subjects: R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords: chitosan - dry powder inhaler - nonviral vector - spray-drying
Publisher: Springer Verlag
ISSN: 0724-8741
Last Modified: 04 Jun 2017 04:05
URI: http://orca.cf.ac.uk/id/eprint/32380

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