Labdane-type diterpenes: thermal effects on phospholipid bilayers, incorporation into liposomes and biological activity.
Labd-13(E)-ene-8alpha,15-diol (1) and its derivative labd-13(E)-ene-8alpha-ol-15-yl-acetate (2) are water insoluble biological active molecules and their structures were elucidated using NMR and X-ray techniques. Differential scanning calorimetry (DSC) was applied to study the thermal effects of 1 and 2 on DPPC bilayers. Liposomes composed of egg phosphatidylcholine/dipalmytoylphosphatidylglycerol (9:0.1 molar ratio) were prepared by the thin-film hydration method and were used for incorporating 1 and 2. Free and liposomal 1 and 2 were tested for their activity against human cancer cell lines using the sulphorhodamine B assay. The effect of 1 and 2 on DPPC bilayers caused abolition of the pre-transition temperature, lowering of the main phase transition and reduction of the transition enthalpy only in the presence of cholesterol. The liposomes that have been designed and developed offer high incorporation efficiency; 62.4% (0.369 drug/lipid molar ratio) and 99.7% (0.661 drug/lipid molar ratio) for 1 and 2, respectively. Liposomal 2 showed growth-inhibiting activity against the majority of the tested cell lines.
Matsingou
Christina
C
Department of Pharmaceutical Technology, School of Pharmacy, Panepistimiopolis, Zografou 15771, University of Athens, Athens, Greece.
Hatziantoniou
Sophia
S
Georgopoulos
Aristidis
A
Dimas
Kostas
K
Terzis
Aris
A
Demetzos
Costas
C
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D002152:Calorimetry, Differential Scanning; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000737:chemistry; D018360:Crystallography, X-Ray; D004224:Diterpenes / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes; D044367:Phase Transition; D010743:Phospholipids / Q000737:chemistry*; D012995:Solubility; D013816:Thermodynamics
D000970:Antineoplastic Agents; D004224:Diterpenes; D008051:Lipid Bilayers; D008081:Liposomes; D010743:Phospholipids; D015060:1,2-Dipalmitoylphosphatidylcholine; D002784:Cholesterol