title: Novel Long-Circulating Liposomes Consisting of PEG Modified β-Sitosterol for Gambogic Acid Delivery.
abstract: Long-circulating liposome is an effective formulation in field of cancer treatment. However, high expenditure of formulation and high dose of cholesterol severely restrict its application. In this paper, we developed a method by grafting polyethylene glycol 2000 on β-sitosterol succinic anhydride ester to obtain relatively cheap polyethylene glycol-β-sitosterol conjugates, which were used to prepare long-circulating liposome without cholesterol. Gambogic acid which is an effective antitumor ingredient with very short half-life, was used as a model drug to prepare long-circulating liposome in this research. Meanwhile, the characteristics, pharmacokinetics and distribution of this novel long-circulating liposome were also investigated in comparison with other gambogic acid formulations. Polyethylene glycol-β-sitosterol conjugates were synthesized, different liposomal formulations were also prepared by ethanol injection method, and the obtained nanoparticles were characterized by dynamic light scattering and transmission electron microscope. The long-circulating effect, pharmacokinetics and distribution of gambogic acid in rats were also explored. 1HNMR confirmed that polyethylene glycol-β-sitosterol conjugates were synthesized successfully. Novel long-circulating liposome was successfully prepared by ethanol injection method attaining a entrapment efficiency of 89.4%, exhibiting a homogeneous particle size of 245.2 nm and -24.3 mV zeta potential with smooth continuous surface. This novel long-circulating liposome demonstrated better long-circulating effect than ordinary long-circulating liposome. The novel long-circulating liposome as-prepared not only could reduce cost of grafting polyethylene glycol on macromolecular phospholipid, but also no cholestrol in preparation was applied, expanding the application of liposome as a formulation in the field of lowering blood lipid. Therefore, polyethylene glycol-β-sitosterol conjugates are recommended substitute for polyethylene glycol modified phospholipid to prepare long-circulating liposomes.
authors.forename: Fan
authors.initials: F
authors.lastname: Yu
authors.forename: Xinhui
authors.initials: X
authors.lastname: Tang
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D008081:Liposomes; D046529:Microscopy, Electron, Transmission; D011092:Polyethylene Glycols / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012855:Sitosterols / Q000737:chemistry*; D014018:Tissue Distribution; D044004:Xanthones / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D008081:Liposomes; D012855:Sitosterols; D044004:Xanthones; D011092:Polyethylene Glycols; C025473:gamma-sitosterol; C052659:gambogic acid