Preparation And Pharmacokinetics Characterization Of 5-Fluorouracil Loaded PLGA Nanoparticles

5-Fluorouracil(5-FU) is a classical anti-metabolite chemotherapy to cancer which is one of the most useful drugs in clinical application, and it is useful to many kinds of neoplasm and effective to original or transfer liver cancer. However, 5-FU leads to serious adverse effect, for example Gastrointestinal tract irritation and bone marrow inhibition, the half-life time of 5-FU in vivo is only 10~20 minutes and its bioavailability is very low. Continuous infusion was commonly used to maintain long-time steady concentration. So it is necessary to exploit new slow-release system for 5-FU.This paper was designed to prepare 5-FU loaded nanoparticles(NP) using poly (L-lactic-co-glycolic acid)(PLGA) as the biodegradable materials, and to study the shape characteristics, stability and releasing behavior of the NP in vitro and in vivo. 5-FU loaded PLGA-NP were prepared by double emulsion(W/O/W)-solvent evaporation method. In order to reach submicron size, we used a high pressure homogenizer with a view to obtaining PLGA-NP with a very high grade of monodispersity. The drug loading, encapsulation efficiency were examined by ultraviolet spectrophotometry. In order to gain the best parameters for preparing PLGA-NP, the influences of different factors on average drug loading and incorporation efficiency of PLGA-NP were evaluated and the optimal preparation parameters were selected by orthogonal-designing method using L9(34) table.The shape of the PLGA-NP was observed by transmission electron microscopy (TEM). The mean diameter and the size distribution of NP were determined by photon correlation spectrometry. The results showed that 5-FU loaded PLGA-NP were spherical in shape and the mean size of PLGA-NP was about 85.4 nm, and the encapsulation efficiency of 5-FU loaded PLGA-NP was (64.1±5.3)% and the drug loading was(12.4±0.7)%. In vitro release profiles of 5-FU from the PLGA-NP were obtained by a dissolution test in phosphate buffer solution (PBS, release medium, pH 7.4). The release behavior of the 5-FU loaded PLGA-NP in vitro was fitted to Higuchi's equation: Q=0.0585t1/2+0.0874 (r=0.9923). The release mechanism were erosion and diffusion. The cumulated amount of 5-FU released from PLGA-NP was about 87.3% after 12 days. Experiment in vitro...