Non-viral dried powders for respiratory gene delivery prepared by cationic and chitosan loaded liposomes

Colonna, C., Conti, B., Genta, I. and Alpar, H.O. (2008) Non-viral dried powders for respiratory gene delivery prepared by cationic and chitosan loaded liposomes. International Journal of Pharmaceutics, 364 (1). pp. 108-118. 10.1016/j.ijpharm.2008.07.034.

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DOI: 10.1016/j.ijpharm.2008.07.034

Abstract

The aim of this work was to investigate lipid-based dried powders as transfection competent carriers capable of promoting the expression of therapeutic genes. The lipid-based vectors were prepared by combining different cationic lipids 1,2-dioleoyl-3-trimethylammoniumpropane chloride (DOTAP), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 3β(N(N′,N-dimethylaminoethane) carbamoyl) cholesterol hydrochloride (DC-Chol) or by mixing of anionic lipids (1,2-dimyristoyl-sn-glycero-3-phospocholine (DMPC), 1,2-dimyristoyl-sn-glycero-3-phospho-rac-glycerol sodium salt (DMPG) and chitosan salts. Spray drying of the formulations was performed using carbohydrates as thermoprotectant excipients and some aminoacids as aerosolisation enhancers. Both the lipidic vectors and the dried powders were characterized for morphology, size, zeta potential (Z-potential) and a yield of the process. Agarose gel electrophoresis was used to examine the structural integrity of dehydrated plasmid DNA (pDNA). The biological functionality of the powders was quantified using the in vitro cell transfection. Among the several lipids and lipid–polymer mixtures tested, the best-selected formulations had spherical shape, narrow size distribution (mean diameter < 220 nm, P.I. < 0.250), a positive zeta-potential (>25 mV) with a good yield of the process (>65%). The set-up spray drying parameters allowed to obtain good yield of the process (>50%) and spherically shaped particles with the volume-weighted mean diameter (d[4,3]) < 6 μm in the respirable range. The set-up conditions for the preparation of the lipid dried powders did not adversely affect the structural integrity of the encapsulated pDNA. The powders kept a good transfection efficiency as compared to the fresh colloidal formulations. Lipid-based spray dried powders allowed the development of stable and viable formulations for respiratory gene delivery. In vitro dispersibility and deposition studies are in progress to determine the aerosolisation properties of the powders.

Item Type:Article
Uncontrolled Keywords:Cationic lipids; Chitosan; LPD complexes; Spray drying; Ex vivo transfection; Respiratory gene delivery
Departments, units and centres:Department of Pharmaceutics > Department of Pharmaceutics
ID Code:2121
Journal or Publication Title:International Journal of Pharmaceutics
Deposited By:Library Staff
Deposited On:20 May 2011 15:32
Last Modified:20 May 2011 15:32

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