【摘要】：目的制備精氨酸-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)介導(dǎo)的多西紫杉醇(docetaxel,DTX)脂肪乳簡(jiǎn)稱RGDFOC12-DTX脂肪乳,并考察其抗腫瘤活性。方法以抗腫瘤藥物DTX為模型藥物,以海豹油為油相,卵磷脂為乳化劑,兩親性RGDFOC12為新型膜材,通過高壓乳勻法制備RGDFOC12-DTX脂肪乳。并考察其粒徑、Zeta電位、滲透壓、離心率(Ke)、p H、包封率、體外釋藥行為和抗腫瘤作用效果。結(jié)果 RGDFOC12-DTX脂肪乳粒徑在190~250 nm,Zeta電位在-30~-40 m V,滲透壓在280~320 m Osm·L-1,0.50Ke0.70,p H在6.5~8.0,載藥質(zhì)量濃度為1 000 mg/L,包封率在90%以上。電鏡下觀察RGDFOC12-DTX脂肪乳粒子呈均勻球形。體外釋放實(shí)驗(yàn)顯示RGDFOC12-DTX脂肪乳呈緩釋的特點(diǎn),體外抗腫瘤活性實(shí)驗(yàn)顯示,RGDFOC12-DTX脂肪乳對(duì)各細(xì)胞系有明顯的時(shí)間依賴效應(yīng),且呈現(xiàn)出緩釋的特點(diǎn)。體內(nèi)抗腫瘤活性實(shí)驗(yàn)顯示,RGDFOC12-DTX脂肪乳具有更好的抗腫瘤活性。結(jié)論本文報(bào)道了RGDFOC12-DTX脂肪乳的新劑型及制備方法,該劑型可有效增加藥物的穩(wěn)定性,降低注射時(shí)的刺激性,增強(qiáng)機(jī)體依從性且具有緩釋性和更好的抗腫瘤活性。
[Abstract]:Objective to prepare arginine-glycine-aspartic acid-phenylalanine-lauryl fatty alcohol (arginine-glycine-aspartate-phenylalanine-dodecyl alcohols,RGDFOC12)-mediated docetaxel (docetaxel,DTX) fat emulsion for short RGDFOC12-DTX fat emulsion and to investigate its antitumor activity. Methods RGDFOC12-DTX fat emulsion was prepared by high pressure emulsion homogenization with DTX as model drug, seal oil as oil phase, lecithin as emulsifier and Amphiphilic RGDFOC12 as new membrane material. The particle size, Zeta potential, osmotic pressure, eccentricity (Ke), p H, entrapment efficiency, drug release behavior in vitro and antitumor effect were also investigated. Results the particle size of RGDFOC12-DTX fat milk was 190 脳 250 nm,Zeta potential at-30 Osm 路L-1, osmotic pressure was 280? 320 m Osm 路L-1, osmotic pressure was 0.50 Ke0.70, pH was 6.5? 8.0. the entrapment efficiency of 1000 mg/L, was over 90%. Under electron microscope, RGDFOC12-DTX fat emulsion particles were uniformly spherical. In vitro release test showed that RGDFOC12-DTX fat emulsion showed sustained release. In vitro antitumor activity test showed that RGDFOC12-DTX fat emulsion had obvious time-dependent effect on each cell line and showed sustained release. In vivo antitumor activity test showed that RGDFOC12-DTX fat emulsion had better antitumor activity. Conclusion A new dosage form and preparation method of RGDFOC12-DTX fat emulsion are reported in this paper. the dosage form can effectively increase the stability of the drug, reduce the irritation during injection, enhance the compliance of the body, and has sustained release and better antitumor activity.
【作者單位】： 首都醫(yī)科大學(xué)化學(xué)生物學(xué)與藥學(xué)院藥劑系;
【基金】：“十二五”重大新藥創(chuàng)制科技重大專項(xiàng)(2011ZX09302-007-01)~~
【分類號(hào)】：R943;R96

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