Cytotoxic and antitumor activity of liposome-incorporated sclareol against cancer cell lines and human colon cancer xenografts.
The aim of this study was to design and prepare liposome-incorporated sclareol--a highly lipophilic natural product-to overcome its water insolubility and develop suitable formulations for in vivo administration. The bioactive labdane-type diterpene sclareol was incorporated into liposomes composed of egg phosphatidylcholine and dipalmitoylphosphatidylglycerol prepared by the thin-film hydration method followed by sonication. A formulation of egg phosphatidylcholine/dipalmitoylphosphatidylglycerol/sclareol (9:0.1:5 molar ratio) was developed and characterized. The lipid recovery and the sclareol to lipid molar ratio were measured using high-performance thin-layer chromatography/flame ionization detection. In vitro drug release was measured in supplemented RPMI-1640 at 37 degrees C. The liposomal and the free sclareol were initially tested in vitro for their activity against human cancer cell lines using the sulphorhodamine B assay. Liposomes incorporating sclareol at a drug to lipid molar ratio of 0:43, suggesting an incorporation efficiency of almost 80%, showed reduced growth rate of human colon cancer tumors (HCT116) developed in SCID mice, without any significant side effects.
Hatziantoniou
Sophia
S
Department of Pharmaceutical Technology, School of Pharmacy, Panepistimiopolis, University of Athens, Greece.
Dimas
Konstantinos
K
Georgopoulos
Aristidis
A
Sotiriadou
Nektaria
N
Demetzos
Costas
C
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use / Q000633:toxicity; D045744:Cell Line, Tumor; D029758:Cistus; D003110:Colonic Neoplasms / Q000188:drug therapy; D004224:Diterpenes / Q000008:administration & dosage* / Q000627:therapeutic use / Q000633:toxicity; D045325:HCT116 Cells; D006801:Humans; D008081:Liposomes; D008297:Male; D051379:Mice; D008517:Phytotherapy; D012116:Resins, Plant / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D004224:Diterpenes; D008081:Liposomes; D012116:Resins, Plant; C070760:sclareol