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doi:10.1016/j.bbamem.2006.01.002    
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Copyright © 2006 Elsevier B.V. All rights reserved.

Effects of trehalose on the phase behavior of DPPC–cholesterol unilamellar vesicles

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Satoshi Ohtakea, Carolina Scheborb, 1 and Juan J. de Pabloa, Corresponding Author Contact Information, E-mail The Corresponding Author

aChemical and Biological Engineering Department, University of Wisconsin, 1415 Engineering Drive, Madison, WI 53706, USA

bDepartamento de Industrias, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, (1428) Ciudad Autónoma de Buenos Aires, Argentina


Received 12 August 2005; 
revised 6 January 2006; 
accepted 6 January 2006. 
Available online 27 January 2006.

Abstract

A systematic study is presented of the effects of trehalose on the physical properties of extruded DPPC–cholesterol unilamellar vesicles. Particular emphasis is placed on examining how the interactions present in the hydrated state translate into those in the dehydrated state. Observations from HSDSC and DSC are used to examine the phase behavior of hydrated and dehydrated vesicles, respectively. The concentration of trehalose inside and outside the vesicles is manipulated, and is shown to affect the relative stability of the membranes. Our results show for the first time that a combination of high inner and low outer trehalose concentration is able to decrease the gel-to-liquid crystalline phase temperature (Tm), while any other combination will not. Upon dehydration, the Tm of all lipid mixtures increases. The extent of the increase depends on the trehalose distribution across the bilayer. The Tm changes in the same direction with trehalose concentration for both freeze-dried and fully hydrated samples, suggesting that the trehalose distribution across the vesicle membrane, as well as the trehalose–phospholipid interaction, is maintained upon lyophilization. The results presented in this work may aid in the formulation of systems to be used in the lyophilization of liposomes for drug delivery applications.

Keywords: Trehalose; DPPC; Cholesterol; Liposome

Article Outline

1. Introduction
2. Materials and methods
2.1. Chemicals
2.2. Sample preparation
2.3. Differential scanning calorimetry
2.4. Water content analysis
2.5. Vesicle size determination
3. Results and discussion
3.1. Effects of Trehalose on the Phase Transitions of Hydrated DPPC Vesicles
3.2. Effects of trehalose on the phase transitions of hydrated DPPC–cholesterol vesicles
3.3. Effects of trehalose on the phase transitions of freeze-dried DPPC–cholesterol vesicles
4. Conclusions
Acknowledgements
References






Corresponding Author Contact InformationCorresponding author. Tel.: +1 608 262 7727; fax: +1 608 262 5434.
1 Member of CONICET, Argentina.

 
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