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Novel nanoparticles for pulmonary gene delivery [Abstract]

Bains, Baljunder Kaur, Taylor, Glyn, Toon, R. and Birchall, James Caradoc 2007. Novel nanoparticles for pulmonary gene delivery [Abstract]. Pharmacy and Pharmacology 59 (S1) , A31-A32. 10.1211/002235707781850140

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Abstract

Objectives A number of respiratory diseases could potentially benefit from gene transfer to the lung, including cystic fibrosis, asthma and emphysema. Jet nebulisation, the current standard for introducing gene therapy formulations into the lung, is highly inefficient. While newer nebuliser technologies are under development, pressurised metered dose inhalers (pMDIs) offer an alternative with potential advantages of more efficacious and rapid administration. As both solution and suspension pMDI formulations have drawbacks relating to stability and dose reproducibility, we aim to explore the potential of modifying a novel low-energy nanotechnology process (Dickinson et al 2001) to prepare surfactant-coated plasmid DNA (pDNA) nanoparticles for pulmonary gene delivery via a dispersion pMDI. Methods Water-in-oil microemulsions containing pEGFP-N1 reporter plasmid were prepared from sucrose solution (as cryoprotectant and aqueous phase), lecithin: propan-2-ol (as stabilising surfactant) and iso-octane (as organic phase). Resultant microemulsions were snap frozen in liquid nitrogen and lyophilised. Excess surfactant was removed by repeated washes with iso-octane and centrifugation. Scanning electron microscopy (SEM) and gel electrophoresis were used to characterise surface morphology and deduce pDNA integrity, respectively. Results A ternary phase diagram was constructed to identify optimised microemulsion compositions (Figure 1). Microemulsions with a surfactant to water ratio of 1.5 and above formed stable water in oil isotropic systems. Unstable biphasic systems were formed when the surfactant to water ratio fell below 1.5. Optimised formulations resulted in effective incorporation of pDNA into the aqueous pool of reverse micelles. Controlled lyophilisation enabled the formation of novel surfactant- coated pDNA nanoparticles. A qualitative analysis performed using gel electrophoresis showed that the freeze-dried particles retained pDNA structural integrity. SEM images conferred aggregates of DNA-cryoprotectant particles. Conclusions Freeze-drying pDNA microemulsions produced surfactant coated pDNA particles whilst successfully maintaining the integrity of the pDNA. The nanotechnology process used offers the potential for the incorporation of pDNA nanoparticles into pMDI systems for pulmonary delivery of gene vectors.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Additional Information: Special Issue: BPC Science Abstracts. Abstract 83 for 2007 Royal Pharmaceutical Society of Great Britain
Publisher: Wiley-Blackwell
ISSN: 0022-3573
Last Modified: 04 Jun 2017 01:56
URI: http://orca-mwe.cf.ac.uk/id/eprint/6421

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