Preparation and release characteristics of 5-flourouracil loaded PLGA-nanoparticles

Aim: To prepare 5-fluorouracil (5-FU) loaded nanoparticles using the biodegradable materials-poly (L-lactic-co-glycolic acid) (PLGA), and to study the shape characteristics and in vitro and in vivo release behaviors of the nanoparticles. Methods: 5-FU loaded nanoparticles (NPs) were made by double emulsion (W/ O/W)-solvent evaporation method with PLGA being used as carrier materials. A high pressure homogenizer was used with a view to obtain NPs with a very high grade of monodispersity. The shape of the nanoparticles was observed by TEM. The mean diameter and the size distribution of nanoparticles were determined by photon correlation spectrometry. The drug loading, incorporation efficiency and releasing behavior of 5-FU-PLGA-NPs in vitro were examined by ultraviolet spectrophotometry. The 5-FU releasing characteristics in vivo were investigated by HPLC after ig administration. Results: 5-fluorouracil loaded PLGA nanoparticles were spheric with the mean size of 85.4 nm; and drug loading and encapsulation efficiency were estimated to be 10.6% and 52.7%, respectively. In vitro release behavior could be discribed by the Higuchi equation: Q = 5.851 6t^1/2 + 8.735 (r = 0.992 3). The plasma level profiles of 5-FU solution and 5-FU-PLGA-NPs in vivo were fitted a two-compartment model after ig dosing. In control group, the half life (t_1/2), t_max and AUC of 5-FU solution was 0.36 h, 0.26 h and 18.15 μg·h/mL, respectively. Comparing with 5-FU solution, t_1/2, t_max and AUC of 5-FU-PLGA-NPs was 2.35 h, 1.13 h and 41.09 μg · h/mL, respectively. Conclusion: 5-FU can be encapsuled in PLGA-nanoparticles and the 5-FU-PLGA-NPs showed significant sustained release in vivo. 5-FU-PLGA-NPs could change the pharmacokinetics of 5-FU, prolong the circulation time in vivo and make a slow release.