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J Control Release. 2009 May 5;135(3):218-26. doi: 10.1016/j.jconrel.2009.01.009. Epub 2009 Jan 23.

Stimuli responsive liquid crystals provide 'on-demand' drug delivery in vitro and in vivo.

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1
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, Victoria 3052, Australia.

Abstract

Lipid-based liquid crystalline materials have been proposed as controlled drug delivery systems. Differences in liquid crystal nanostructure have previously been shown to change drug diffusion and hence release, however there has been little progress towards the use of in situ changes to nanostructure to control drug release. In this study, phytantriol and glyceryl monooleate-based bicontinuous cubic (Q2) and inverse hexagonal (H2) nanostructures have been designed to allow change to the nanostructure in response to external change in temperature, with a view to controlling drug release rates in vivo. Changes to nanostructure with temperature were confirmed by crossed polarised optical microscopy and small angle X-ray scattering. Phytantriol containing 3% (w/w) vitamin E acetate provided the necessary phase transition behaviour to progress this system to in vitro release and in vivo proof of concept studies. Using glucose as a model hydrophilic drug, drug diffusion was shown to be reversible on switching between the H2 and Q2 nanostructures at temperatures above and below physiological temperature respectively. An in vivo proof of concept study in rats showed that after subcutaneous administration of these materials, the changes in nanostructure induced by application of a heat or cool pack at the injection site stimulated changes in drug release from the matrix anticipated from in vitro release behaviour, thereby demonstrating the potential utility of these systems as 'on demand' drug release delivery vehicles.

PMID:
19331865
DOI:
10.1016/j.jconrel.2009.01.009
[Indexed for MEDLINE]

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