摘要
目的制备洛莫司汀热敏脂质体并考察其体外抗肿瘤活性。方法以二棕榈酰-D,L-α磷脂酰胆碱(DPPC)和胆固醇为载体,采用薄膜分散法制备洛莫司汀热敏脂质体,以甘露醇为赋形剂将其制成冻干脂质体;透射电镜观察冻干前后脂质体的形态,激光散射法测定脂质体的粒径分布及Zeta电位;Sephadex G-50柱分离脂质体与未包封药物,HPLC测定脂质体包封率;并考察脂质体的体外释药特性和体外抗肿瘤活性。结果脂质体为多层圆形或椭圆型小囊,无粘连,大小均匀,冷冻干燥前后平均粒径分别为189.8和274.9 nm;ζ电位分别为-19.13和-0.83 mV,包封率分别为68.28%和60.32%(n=3)。在pH7.4 PBS介质、相变温度42℃时30 min累积释药88.64%。相同剂量洛莫司汀溶液与洛莫司汀热敏脂质体比较,37℃时肿瘤抑制率分别为33.04%和35.35%,两者无明显差异(P>0.05);加热到42℃时肿瘤抑制率明显增加,加热10 min肿瘤抑制率分别为36.75%和58.87%;加热30 min肿瘤抑制率分别为50.52%和71.69%。结论洛莫司汀热敏脂质体在相变温度时,体外释药明显增加,体外抑瘤效果明显提高。
OBJECTIVE To prepare Lomustine thermo-sensitive liposomes（CCNU-TSL） and investigate the anti-tumor activity in vitro. METHODS The CCNU-TSL were prepared by film dispersion method using L-α- Dipalmitoyl-rae-glyeero-3-phosphoeholine （DPPC） and cholesterin as carrier materials, and then to freeze drying using Mannitol as eryoproteetant. The morphologies of CCNUTSL before and after eryodesieeation were observed by transmission electron microscope. The Zeta potential and the particle size distribution were evaluated by the laser scattering technique. The liposomes and the free drug were separated by sephadex G -50 column and the entrapment effieieneies were determined by HPLC. The release characteristics and anti-tumor activities of CCNU-TSL in vitro were investigated. RESULTS The CCNU-TSL was multi-player spherical or ellipsoidal shape with uniform sizes. The mean diameters （D50） of CCNU-TSL before and after eryodesieeation were 189. 8 and 274. 9 nm, respectively. The Zeta potentials were - 19. 13 and -0. 83 mV, respectively. The average entrapment effieiencies were 68.28% and 60. 32% , respectively. The accumulative drug release percent was 88. 64% in PBS（pH 7. 4） at 42 ℃. The tumor inhibition rate of the CCNU-TSL and lomustine solution at the same doses were 35.35 % and 33.04% at 37 ℃, respectively （P 〉 0. 05 ）, and the tumor inhibition rates were increased dramatically at 42 ℃. The tumor inhibition rate of Lomustine solution and CCNU-TSL were 36. 75% and 58.87% at 42 ℃ for 10 min,respeetively. And the tumor inhibition rate were 50. 52% and 71.69% at 42 ℃ for 30 min, respectively. CONCLUSION The drug release percents and the tumor control rates of CCNU-TSL are improved significantly compared with lomustine solution in vitro.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2007年第12期914-918,共5页
Chinese Pharmaceutical Journal
