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Time-Resolved Small-Angle Neutron Scattering as a Tool for Studying Controlled Release from Liposomes using Polymer-Enzyme Conjugates

Ferguson, Elaine Lesley, De Luca, Edoardo, Heenan, Richard K., King, Stephen M. and Griffiths, Peter Charles 2010. Time-Resolved Small-Angle Neutron Scattering as a Tool for Studying Controlled Release from Liposomes using Polymer-Enzyme Conjugates. Macromolecular Rapid Communications 31 (19) , pp. 1685-1690. 10.1002/marc.201000241

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Abstract

The action of phospholipase A2 (PLA2) on 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes (vesicles) – an integral component in the polymer enzyme liposome therapy (PELT) mechanism (R. Duncan et al., J. Controlled Release2001, 74, 135) for the controlled delivery of poorly soluble therapeutic molecules within liposomes – may be “masked” by conjugation to the biodegradable polymer dextrin and subsequently regenerated by the endogenous enzyme -amylase that degrades the dextrin; that is, incorporating the so-called polymer-unmasked-masked protein therapy (PUMPT) approach (R. Duncan, et al. Biomacromolecules2008, 9, 1146). Small-angle neutron scattering (SANS) has been used to quantify the detailed structure of DPPC liposomes and any perturbation in that structure induced by the presence of PLA2 in native, “masked” (dextrin–PLA2 conjugate) and an in situ -amylase-unmasked form. A time-dependent degradation of the vesicular structure was observed for the two active PLA2 cases, but not for the masked case. This study demonstrates that the PLA2-induced hydrolysis of the DPPC – and the associated rupture of the liposome and the release of the enclosed material – may be controlled through masking with dextrin. Accordingly, the viability of using such a combinatorial nanomedicine approach as a general route for the controlled delivery of poorly soluble therapeutic molecules is shown.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Chemistry
Dentistry
Subjects: Q Science > QD Chemistry
R Medicine > RS Pharmacy and materia medica
Uncontrolled Keywords: controlled release; liposomes; polymer-enzyme conjugates; small-angle neutron scattering; vesicles
Publisher: Wiley
ISSN: 1022-1336
Last Modified: 04 Jun 2017 02:08
URI: http://orca-mwe.cf.ac.uk/id/eprint/9747

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