title: The efficacy and safety of bufadienolides-loaded nanostructured lipid carriers.
abstract: 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.
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Weng
authors.forename: Lihui
authors.initials: L
authors.lastname: Wang
authors.forename: Haibing
authors.initials: H
authors.lastname: He
authors.forename: Jingyu
authors.initials: J
authors.lastname: Yang
authors.forename: Xing
authors.initials: X
authors.lastname: Tang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D002018:Bufanolides / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003840:Deoxycholic Acid / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding; D005079:Excipients / Q000737:chemistry; D005260:Female; D005989:Glycerides / Q000737:chemistry; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D007275:Injections, Intravenous; D007928:Lethal Dose 50; D008055:Lipids / Q000737:chemistry*; D008297:Male; D051379:Mice; D049329:Nanostructures; D019301:Oleic Acid / Q000737:chemistry; D020442:Poloxamer / Q000737:chemistry; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D012510:Sarcoma 180 / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013678:Technology, Pharmaceutical / Q000379:methods; D014018:Tissue Distribution; D014280:Triglycerides / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D002018:Bufanolides; D004337:Drug Carriers; D005079:Excipients; D005989:Glycerides; D008055:Lipids; D014280:Triglycerides; D003840:Deoxycholic Acid; D020442:Poloxamer; C048159:glyceryl monostearate; D019301:Oleic Acid