Principles of rational design of thermally targeted liposomes for local drug delivery

Abstract

Drug release from 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes occurs close to the main transition temperature Tm=41°C. The exact release temperature can be adjusted by additional lipids, which shift Tm. A major issue is drug leakage at 37°C. We here describe a novel approach with improved drug retention yet rapid release. To obtain spherical, smooth liposomes we included: i) 2mol% cholesterol, to soften bilayers (Lemmich et al 1997), ii) lipids, which due to their spontaneous curvature stabilize the negative and positive curvatures of the inner and outer leaflets of unilamellar liposomes. In addition to differential scanning calorimetry (DSC) and fluorescence spectroscopy, the lipid mixtures were analyzed by a Langmuir balance for their elastic properties and lipid packing, aiming at high elasticity modulus CS(-1). Maxima in CS(-1) coincided with minima in the free energy of lateral mixing. These liposomes have reduced drug leakage, yet retain rapid release.

From the clinical editor: This paper reports the development of optimized DPPC liposomes for drug delivery, with reduced drug leakage but maintained rapid release.

Keywords: Controlled drug release; Doxorubicin; Elasticity; Liposomes; Phase transition.