5-氟尿嘧啶PLGA纳米粒的制备及其体内外释药研究

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

目的:以生物可降解材料乳酸-乙醇酸共聚物(PLGA)制备5-氟尿嘧啶(5-FU)纳米粒,并对其进行体内外释药研究。方法:采用复乳-溶剂挥发法结合高压均质法制备5-FU-PLGA纳米粒。用透射电镜观察纳米粒的形态,并对5-FU-PL-GA纳米粒的粒径及其分布、载药量、包封率和体内外释药进行了研究。结果:制得的5-FU-PLGA纳米粒为类球形实体粒子,平均粒径为85.4 nm,载药量为10.6%,包封率为52.7%,体外释药符合Higuchi方程:Q=5.851 6t1/2+8.735(r=0.9923)。5-FU水溶液组在体内半衰期(t1/2)仅为0.36 h,tmax为0.26 h,AUC为18.15μg.h/mL,而同剂量的5-FU-PLGA纳米粒在体内t1/2为2.35 h,tmax为1.13 h,AUC为41.09μg.h/mL。结论:制得的5-FU-PLGA纳米粒可改变5-FU体内的药代动力学行为,延长5-FU在体内的循环时间,具有明显的缓释作用,口服吸收好,生物利用度有明显提高。

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 cartier 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. Rosults：5-fluomuracil 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 = 5.8516t^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 （t1/2）, tmax and AUC of 5-FU solution was 0.36 h, 0.26 h and 18.15μg·h/mL, respectively. Comparing with 5-FU solution, t1/2, tmax and AUC of 5-FU-PLGA-NPs was 2.35 h, 1.13 h and 41.09μg·h/mL, respectively. Gonclusion：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.