Preparation and Body Distribution of Freeze-Dried Powder of Ursolic Acid Phospholipid Nanoparticles
- 1 March 2009
- journal article
- research article
- Published by Taylor & Francis Ltd in Drug Development and Industrial Pharmacy
- Vol. 35 (3), 305-310
- https://doi.org/10.1080/03639040802302165
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 AUC0–12 ratio of UA-PL-NP in liver to that in plasma was much higher than that of UA-Sol, and the liver AUC0–12 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.Keywords
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