Bipolar tetraether lipids derived from thermoacidophilic archaeon Sulfolobus acidocaldarius for membrane stabilization of chlorin e6 based liposomes for photodynamic therapy.
The initial burst release of water-soluble photosensitizers is one of the major problems encountered the development of controlled release formulations. In this study, the freely water soluble chlorin e6 (Ce6) was assembled with cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) to improve its loading efficiency in the liposomal bilayer. Tetraether lipids (TELs) derived from Sulfolobus acidocaldarius were added to DOTAP:Ce6 assembly in a concentration range of 2.5×10(-4)-1.6×10(-3)M to stabilize the membrane rigidity of the liposomes and to provide controlled release system. From the comparative spectroscopic experiments, it has been shown that the assembled DOTAP:Ce6 along with addition of TELs have improved the loading efficiency of Ce6 in TELs-liposomes and obviously modified the release profile of Ce6. The in vitro cell viability of Ce6 in mouse neuro-blastoma (Neuro-2a) and ovarian cell carcinoma (SK-OV-3) confirmed neglected dark cytotoxicity and presented potential photo-induced cytotoxicity with the effect was being more pronounced in Neuro 2a than in SK-OV-3. In-situ IV-injection of chick chorioallantoic membrane (CAM) showed hemorrhage and necrosis 30 min post irradiation at 1.8 mol% TELs (19.9J/cm(2)). Higher TELs of 2.2 and 3.7 mol% in particular demonstrated localized vascular destruction within the irradiated area. Our results suggest that TELs favored slower release rates of Ce6. This, in turn, tetraether lipids can be considered as a versatile class of lipids for photodynamic modality for destruction of cancer cells and tumor vasculature while sparing the quiescent ones.
Department of Pharmaceutical Technology and Biopharmaceutics, Marburg University, Ketzerbach 63, 35037 Marburg, Germany; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Helwan University, Ain Helwan, 11795 Cairo, Egypt.
Gihan
G
Mahmoud
Department of Pharmaceutical Technology and Biopharmaceutics, Marburg University, Ketzerbach 63, 35037 Marburg, Germany.
Jarmila
J
Jedelská
Department of Pharmaceutical Technology and Biopharmaceutics, Marburg University, Ketzerbach 63, 35037 Marburg, Germany.
Boris
B
Strehlow
Department of Pharmaceutical Technology and Biopharmaceutics, Marburg University, Ketzerbach 63, 35037 Marburg, Germany. Electronic address: ubakowsky@aol.com.
Udo
U
Bakowsky
D000818:Animals; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000737:chemistry* / Q000187:drug effects; D002642:Chick Embryo; D002645:Chickens; D002735:Chlorophyllides; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D008055:Lipids / Q000008:administration & dosage / Q000737:chemistry*; D008081:Liposomes; D051379:Mice; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000737:chemistry*; D011166:Porphyrins / Q000008:administration & dosage / Q000737:chemistry*; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage / Q000737:chemistry; D016945:Sulfolobus acidocaldarius
D002735:Chlorophyllides; D005229:Fatty Acids, Monounsaturated; D008055:Lipids; D008081:Liposomes; D017319:Photosensitizing Agents; D011166:Porphyrins; D000644:Quaternary Ammonium Compounds; C062985:phytochlorin; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane
Chlorin e6; Liposomes; Photodynamic therapy; Photosensitizer; Tetraether lipids