Title

trans-2-Aminocyclohexanol-based lipids as pH-sensitive conformational switches in liposomes for drug delivery

Document Type

Conference Presentation

Conference Title/Conference Publication

244th National Meeting and Exposition of American Chemical Society (ACS)

Organization

American Chemical Society (ACS)

Location

Philadelphia, PA

Conference Dates

August 19-23, 2012

Date of Presentation

8-21-2012

ISSN

2572-6803

Abstract

We developed a novel strategy to render liposomes pH-sensitive: a protonation-induced conformational switch of lipid tails, using trans-2-aminocyclohexanol moiety (TACH) as a molecular trigger. Amino and hydroxy groups of a TACH-lipid are in axial positions at pH 7.4 while both lipidic groups COOCnH(2n+1) adopt equatorial positions (A ). At lower pH relevant to many physiological/pathological scenarios, the amine nitrogen is protonated to form a strong hydrogen bond with the hydroxy group, forcing both groups into equatorial position. Such switch is mechanically transmitted via the conformational flip of the ring to turn both ester groups into axial position (B H+), thereby drastically increasing the spatial separation of the lipid tails. In lipid membranes, TACH-lipids of this type produce liposomes with extraordinary characteristics: an instant release of their cargo in response to a weakly acidic medium combined with high stability in storage and in serum.

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