Cellular uptake of solid lipid nanoparticles and cytotoxicity of encapsulated paclitaxel in A549 cancer cells.
The aim of this study was to investigate the cellular uptake of solid lipid nanoparticles (SLN) and cytotoxicity of its paclitaxel delivery system. The conjugate of octadecylamine-fluorescein isothiocyanate (ODA-FITC) was synthesized, and used as a marker to prepare fluorescent SLN. The cellular uptakes of fluorescent SLN with different lipid material were evaluated by fluorescence microscopy and the measurement of fluorescence intensity. The order of cellular uptake ability was glycerol tristearate SLN>monostearin SLN>stearic acid SLN>Compritol 888 ATO SLN (ATO888 SLN). The cellular cytotoxicities of paclitaxel were highly enhanced by the encapsulation of lipid matrix. Due to the lower drug entrapment efficiency of glycerol tristearate SLN, monostearin SLN was considered as the best lipid material to improve the cytotoxicity of drug. The polyethylene glycol monostearate (PEG-SA) and the synthesized conjugate of folic acid-stearic acid (FA-SA) were further introduced into monostearin SLN, respectively. The PEG and folate modified SLN could enhance the cellular uptake of SLN and the cellular cytotoxicity of drug by the membrane disturb ability of PEG chains on the SLN surface and the improved endocytosis mediated by folate receptor.
Yuan
Hong
H
College of Pharmaceutical Science, Zhejiang University, 388 Yuhangtang Road, Hangzhou 310058, People's Republic of China.
Miao
Jing
J
Du
Yong-Zhong
YZ
You
Jian
J
Hu
Fu-Qiang
FQ
Zeng
Su
S
D000588:Amines / Q000737:chemistry; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D005227:Fatty Acids / Q000737:chemistry; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D005492:Folic Acid / Q000737:chemistry; D005989:Glycerides / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D008055:Lipids / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D017239:Paclitaxel / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D055672:Static Electricity; D013228:Stearates / Q000737:chemistry; D013229:Stearic Acids / Q000737:chemistry; D013499:Surface Properties; D014280:Triglycerides / Q000737:chemistry
D000588:Amines; D000972:Antineoplastic Agents, Phytogenic; D005227:Fatty Acids; D005989:Glycerides; D008055:Lipids; D013228:Stearates; D013229:Stearic Acids; D014280:Triglycerides; C086409:glyceryl behenate; C048159:glyceryl monostearate; D011092:Polyethylene Glycols; C031183:stearic acid; C009314:polyethylene glycol monostearate; D005492:Folic Acid; C009317:stearylamine; D016650:Fluorescein-5-isothiocyanate; D017239:Paclitaxel