TY - JOUR

T1 - Anticancer double lipid prodrugs

T2 - liposomal preparation and characterization

AU - Arouri, Ahmad

AU - Mouritsen, Ole G.

PY - 2011

Y1 - 2011

N2 - The escape of encapsulated anticancer drugs from liposomes by passive diffusion often leads to suboptimal drug concentrations in the cancer tissue, therefore calling for effective trigger mechanisms to release the drug at the target. We investigated mixtures of lipid components that not only form stable liposomes, but also can be turned into active drugs by secretory phospholipase A2 (sPLA2), an enzyme that is upregulated in various cancer cells, without the necessity for conventional liposome drug loading. The liposomes are composed of a novel lipid-based retinoid prodrug premixed with saturated phospholipids. The prodrug is found to be miscible with phospholipids, and the lipid mixtures are shown to form liposomes with the desired size distribution. The preparation procedure, phase behavior, and physicochemical properties of the formed liposomes are described as a function of lipid composition. We show that the premixing of the prodrug with phospholipids can be used to modify the physicochemical properties of liposomal formulations. The results should prove useful for further exploration of the potential for using these novel lipid prodrugs in liposomal formulations for cancer treatment.

AB - The escape of encapsulated anticancer drugs from liposomes by passive diffusion often leads to suboptimal drug concentrations in the cancer tissue, therefore calling for effective trigger mechanisms to release the drug at the target. We investigated mixtures of lipid components that not only form stable liposomes, but also can be turned into active drugs by secretory phospholipase A2 (sPLA2), an enzyme that is upregulated in various cancer cells, without the necessity for conventional liposome drug loading. The liposomes are composed of a novel lipid-based retinoid prodrug premixed with saturated phospholipids. The prodrug is found to be miscible with phospholipids, and the lipid mixtures are shown to form liposomes with the desired size distribution. The preparation procedure, phase behavior, and physicochemical properties of the formed liposomes are described as a function of lipid composition. We show that the premixing of the prodrug with phospholipids can be used to modify the physicochemical properties of liposomal formulations. The results should prove useful for further exploration of the potential for using these novel lipid prodrugs in liposomal formulations for cancer treatment.

KW - Anticancer prodrug

KW - Lipid mixture

KW - NBDdithionite interaction

KW - Secretory phospholipase A2 (sPLA2)

KW - Triggered drug release

U2 - 10.3109/08982104.2011.563365

DO - 10.3109/08982104.2011.563365

M3 - Journal article

C2 - 21438721

AN - SCOPUS:80054699811

VL - 21

SP - 296

EP - 305

JO - Journal of Liposome Research

JF - Journal of Liposome Research

SN - 0898-2104

IS - 4

ER -