Preparation and body distribution of freeze-dried powder of ursolic acid phospholipid nanoparticles.
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.
Zhou
Xiao Ju
XJ
State Key Laboratory of Virology, College of Pharmacy, Wuhan University, Wuhan, P.R., China.
Hu
Xian Ming
XM
Yi
Yi Mu
YM
Wan
Jing
J
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
D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D010743:Phospholipids; D020442:Poloxamer; D014315:Triterpenes; D000097245:Ursolic Acid