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.

Preparation and distribution of 5-fluorouracil (125)I sodium alginate-bovine serum albumin nanoparticles.

AIM:To prepare 5-FU sodium alginate(125)I bovine serum albumin nanoparticles (BSA NP), to determine the radioactive count in different organs of rats at different time points after oral administration of 5-FU (125)I sodium alginate-BSA NP and to calculate the kinetic parameters of its metabolism.METHODS:Emulsion solidification method was used to prepare 5-FU (125)I sodium alginate-BSA NP, and to determine its diameter under transmission electronic microscope (TEM). Then the rate of NP and external drug releasing velocity were measured. Radioactive counting in different organs of rats was made after oral administration of the NP by GAMA Counter, and the kinetic parameters of drug metabolism were calculated by handling the data with the two-department model.RESULTS:The average arithmatic diameter of the NP was 166nm ± 34nm, the rate of 5-FU was 32.8% and the cumulative external releasing ratio amounted to 84.0% within 72 hours. The NP was mainly distributed in the liver, spleen, lungs and kidneys after NP oral administration to rats. The micro-radioautographic experiment showed that NP was distributed in the Kupffers cells of liver, liver parenchymal cells and the phagocytes of spleen and lungs. The kinetic parameters of matabolism were: T(1/2) = 9.42h, C(max) = 2.45X10(7)Bq,T(max) = 2.18h, AUC = 148X10(9)Bq.CONCLUSION:NP is difficult to pass through the blood-cerebral barrier,and (125)I sodium alginate-BSA NP enters the body-circulation by gastroin testinal passage.