title: Preparation and body distribution of freeze-dried powder of ursolic acid phospholipid nanoparticles.
abstract: Ursolic acid (UA) is a poor soluble natural triterpenoid. It has a wide variety of antitumor activities. We extracted it from Crataegus pinnatifida for the first time. To achieve a high bioavailability, targeting effect, stability, and an intravenous (i.v.) administration, the UA phospholipid nanopowders (UA-PL-NP) were prepared, characterized, and evaluated. With soybean phospholipid as the carrier and poloxamer 188 as emulsifier, the UA nanoparticle suspension was prepared by solvent emulsification-evaporation and ultrasonic dispersion. The UA-PL-NP was obtained by freeze drying. The body distribution in mice was studied after i.v. administration of UA-PL-NP and an UA control solution (UA-Sol). The entrapment efficiency (EE) and UA concentration in vitro and in vivo were analyzed by high-performance liquid chromatography (HPLC). The results showed that the UA-PL-NP had an average diameter of 273.8 nm with a zeta potential of -23.2 mV. The EE was up to 86.0%, and the drug loading (DL) was 12.8%. After i.v. administration of UA-PL-NP with low, middle and high doses, UA concentration in the livers of mice obviously increased during tested period and was highest in tested organs at 4 h. The AUC(0-12) ratio of UA-PL-NP in liver to that in plasma was much higher than that of UA-Sol, and the liver AUC(0-12) ratio of UA-PL-NP to UA-Sol was 8.6. These results indicate the UA-PL-NP have a good targeting to the liver after i.v. administration. Therefore, the UA-PL-NP is demonstrated to be available as an i.v. and liver targeting system for lipophilic antitumor triterpenoids.
authors.affiliation: State Key Laboratory of Virology, College of Pharmacy, Wuhan University, Wuhan, P.R., China.
authors.forename: Xiao Ju
authors.initials: XJ
authors.lastname: Zhou
authors.forename: Xian Ming
authors.initials: XM
authors.lastname: Hu
authors.forename: Yi Mu
authors.initials: YM
authors.lastname: Yi
authors.forename: Jing
authors.initials: J
authors.lastname: Wan
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D027825:Crataegus / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D005612:Freeze Drying; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D053758:Nanoparticles; D010743:Phospholipids / Q000737:chemistry; D020442:Poloxamer / Q000737:chemistry; D013025:Glycine max / Q000737:chemistry; D014018:Tissue Distribution; D014315:Triterpenes / Q000302:isolation & purification / Q000493:pharmacokinetics*; D000097245:Ursolic Acid
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D010743:Phospholipids; D020442:Poloxamer; D014315:Triterpenes; D000097245:Ursolic Acid