Triggering Stealth Liposomes by pH-Sensitive Conformational Switch of Lipid Tails

Document Type

Poster

Department

Chemistry

Conference Title

American Association for Pharmacutics (AAPS)

Organization

American Association for Pharmacutics (AAPS)

Location

Los Angeles, CA

Conference Dates

November 8-12, 2009

Date of Presentation

11-8-2009

Abstract

Purpose. To characterize the ability of a novel pH-sensitive lipid to trigger the release of PEG-grafted liposomes as potential drug delivery systems.

Methods. A number of liposomes were constructed by freeze-thawing and extrusion. The liposomes comprised PEG-lipid conjugates, phospholipids, and the pH-sensitive lipid carrying a trans-2-aminocyclohexanol headgroup as a pH-sensitive conformational switch of lipid tails. The liposomes also contained the fluorescent dyes ANT/DPX so that liposome permeation can be monitored by the release of the dyes, which de-quenches their fluorescence. The liposomes were incubated in buffers of different pHs at 37 C and the change of the fluorescence of the samples were monitored on a QuataMaster Fluorometer. The data were then converted into the Rich Text format and processed by Microsoft Excel to give the percentage of liposome leakage over time.

Results. At pH 7.4, most of the constructed liposomes carried homogenous size and near-zero Zeta potential. The liposomes can be stored at pH 7.4, 4 C for months. Upon exposure to pH 5.5, the liposomes released their encapsulated dyes. The extend of liposome contents release at the lowered pH depended on the percentage of the pH-sensitive lipid and the nature of the phospholipids.

Conclusion. Conformational switch of the lipid tails has been validated as a versatile approach to render PEG-grafted liposomes pHsensitive. Such pH-sensitive and yet "stealth" liposomes may be used as more effective anticancer drug delivery systems compared to traditional stealth liposomes.

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