deoxycholic-acid and Sarcoma-180

Bufadienolides-loaded nanostructured lipid carriers (BU-NLC) were prepared for parenteral application using glyceryl monostearate as solid core, medium-chain triglyceride and oleic acid as liquid lipid material, and Lipoid E-80, sodium deoxycholate and pluronic F68 as stabilizers. In this study, the in vitro cytotoxicity, pharmacokinetics, biodistribution, antitumor efficacy and safety of BU-NLC were evaluated. Against human astrocytoma cell line (U87-MG) and human gastric carcinoma cell line (HGC-27) BU-NLC exhibited cytotoxicity that was similar to that of the free drug, and superior to that of the commercially available fluorouracil injection. BU-NLC exhibited a linear pharmacokinetic behavior at doses ranging from 0.25 to 1.0 mg/kg. The improved pharmacokinetic profile of bufadienolides when formulated in BU-NLC resulted in a higher plasma concentration and lower clearance after intravenous administration compared with bufadienolides solution (BU-S). A biodistribution study indicated that bufadienolides were mainly distributed in the lung, spleen, brain and kidney, and the longest retention was observed in the brain. A sarcoma-180 tumor model further confirmed the advantages of BU-NLC versus BU-S. Hemolysis and acute toxicity investigations showed that BU-NLC was safe when given by intravenous injection with reduced toxicity. In conclusion, the NLC system is a promising approach for the intravenous delivery of bufadienolides.

Topics: Animals; Antineoplastic Agents; Bufanolides; Cell Line, Tumor; Cell Proliferation; Chemistry, Pharmaceutical; Deoxycholic Acid; Dose-Response Relationship, Drug; Drug Carriers; Drug Compounding; Excipients; Female; Glycerides; Hemolysis; Humans; Inhibitory Concentration 50; Injections, Intravenous; Lethal Dose 50; Lipids; Male; Mice; Nanostructures; Oleic Acid; Poloxamer; Rabbits; Rats; Rats, Wistar; Sarcoma 180; Technology, Pharmaceutical; Tissue Distribution; Triglycerides