CAJ | 학술논문

目的：制备精氨酸-甘氨酸-天冬氨酸-苯丙氨酸-十二烷基脂肪醇( arginine-glycine-aspartate-phenylalanine-dodecyl alcohols,RGDFOC12)介导的多西紫杉醇( docetaxel,DTX)脂肪乳简称RGDFOC12-DTX脂肪乳,并考察其抗肿瘤活性。方法以抗肿瘤药物DTX为模型药物,以海豹油为油相,卵磷脂为乳化剂,两亲性RGDFOC12为新型膜材,通过高压乳匀法制备RGDFOC12-DTX脂肪乳。并考察其粒径、Zeta电位、渗透压、离心率( Ke)、pH、包封率、体外释药行为和抗肿瘤作用效果。结果 RGDFOC12-DTX脂肪乳粒径在190~250 nm,Zeta电位在-30~-40 mV ,渗透压在280~320 mOsm·L-1,0.50<Ke<0.70,pH在6.5~8.0,载药质量浓度为1000 mg/L,包封率在90%以上。电镜下观察 RGDFOC12-DTX 脂肪乳粒子呈均匀球形。体外释放实验显示RGDFOC12-DTX脂肪乳呈缓释的特点,体外抗肿瘤活性实验显示,RGDFOC12-DTX脂肪乳对各细胞系有明显的时间依赖效应,且呈现出缓释的特点。体内抗肿瘤活性实验显示,RGDFOC12-DTX脂肪乳具有更好的抗肿瘤活性。结论本文报道了RGDFOC12-DTX脂肪乳的新剂型及制备方法,该剂型可有效增加药物的稳定性,降低注射时的刺激性,增强机体依从性且具有缓释性和更好的抗肿瘤活性。
목적：제비정안산-감안산-천동안산-분병안산-십이완기지방순( arginine-glycine-aspartate-phenylalanine-dodecyl alcohols,RGDFOC12)개도적다서자삼순( docetaxel,DTX)지방유간칭RGDFOC12-DTX지방유,병고찰기항종류활성。방법이항종류약물DTX위모형약물,이해표유위유상,란린지위유화제,량친성RGDFOC12위신형막재,통과고압유균법제비RGDFOC12-DTX지방유。병고찰기립경、Zeta전위、삼투압、리심솔( Ke)、pH、포봉솔、체외석약행위화항종류작용효과。결과 RGDFOC12-DTX지방유립경재190~250 nm,Zeta전위재-30~-40 mV ,삼투압재280~320 mOsm·L-1,0.50<Ke<0.70,pH재6.5~8.0,재약질량농도위1000 mg/L,포봉솔재90%이상。전경하관찰 RGDFOC12-DTX 지방유입자정균균구형。체외석방실험현시RGDFOC12-DTX지방유정완석적특점,체외항종류활성실험현시,RGDFOC12-DTX지방유대각세포계유명현적시간의뢰효응,차정현출완석적특점。체내항종류활성실험현시,RGDFOC12-DTX지방유구유경호적항종류활성。결론본문보도료RGDFOC12-DTX지방유적신제형급제비방법,해제형가유효증가약물적은정성,강저주사시적자격성,증강궤체의종성차구유완석성화경호적항종류활성。
Objective To design arginine-glycine-aspartate-phenylalanine-dodecyl alcohols mediated docetaxel lipid emulsion [ RGDFOC12-DTX-LE] and investigate its anti-tumor activity. Methods DTX a broadly used anti-cancer drug, was tested as the model drug. The RGDFOC12-DTX-LE was made of seal oil, lecithin, RGDFOC12 and glycerol. The formulation was obtained by high pressured homogenization. Results The physicochemical property of RGDFOC12-DTX-LE was evaluated by measuring mean particle size(190 nm~250 nm), Zeta potential(-30 mV to -40 mV), eccentricity constants(Ke<0. 7), pH(6. 5~8. 0). Drug entrapment efficiency was greater than 90%. Transmission electron microscopy( TEM) and scanning electron microscopy( SEM) indicated that RGDFOC12-DTX-LEs appeared to be homogeneous and spherical particles. The result of dynamic dialysis method demonstrated that the drug was released from the emulsion slowly. Cytotoxicity studies in HepG2, A375, SH-sy5y, HeLa, MCF-7 cell lines were explored and DTX mixed suspension is the positive control. RGDFOC12-DTX-LE for each cell line had obvious time-dependent effect and presents the characteristics of slow releasing. The in vivo anti-tumor activity experiments showed that RGDFOC12-DTX-LE exhibited better anti-tumor activity. Conclusion In this work RGDF-mediated docetaxel lipid emulsion preparation, had a good in vitro stability, lower injection irritation, enhanced compliance, sustained release property and better anti-tumor effect.