Cholesterol derivatives based charged liposomes for doxorubicin delivery: preparation, in vitro and in vivo characterization.
Cholesterol derivatives based charged liposomes for doxorubicin delivery: preparation, in vitro and in vivo characterization.
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作者：
Nie Y;Ji L;Ding H;Xie L;Li L;He B;Wu Y;Gu Z
胆固醇在脂质体组成中起关键作用。它对脂质体的体内外行为有很大的影响。为了验证胆固醇的电荷、表面屏蔽和化学性质可能产生的影响，合成了两类带电荷和聚乙二醇化胆固醇的脂质体。分别以胆固醇衍生物中的半琥珀酸酯和赖氨酸为电荷，制备了阴离子脂质体（AL）和阳离子脂质体（CL）。以中性脂质体（NL）为对照，考察了不同处方脂质体包封阿霉素后的特性。结果表明，与NL相比，AL和CL脂质体经PEG修饰后，在保持相似的粒径分布、包封率、低细胞毒性和低溶血性的同时，具有较长的滞留释放曲线。共聚焦激光扫描显微镜和流式细胞术实验证实，在小鼠乳腺癌和黑色素瘤细胞，人上皮癌和肝癌细胞中，AL和CL囊泡的细胞摄取显著高于NL。这与我们相应的载阿霉素脂质体的细胞死亡率研究一致。荷电脂质体的体内抗肿瘤作用实验也显示出比NL脂质体高得多的肿瘤抑制作用（70%vs45%，p < 0.05）。这是第一次报道带/不带PEG化的荷电胆固醇脂质体的抗癌作用。通过对脂质体处方的深入了解，对脂质体相关药物的研究和开发具有重要意义。
Cholesterol plays a critical role in liposome composition. It has great impact on the behavior of liposome in vitro and in vivo. In order to verify the possible effects from cholesterol charge, surface shielding and chemical nature, two catalogs of liposomes with charged and PEGylated cholesterols were synthesized. Anionic liposomes (AL) and cationic liposomes (CL) were prepared, with charges from hemisuccinate and lysine in cholesterol derivatives, respectively. Characteristics of different formulated liposomes were investigated after doxorubicin encapsulation, using neutral liposomes (NL) as control. Results showed that after PEGylation, AL and CL liposomes displayed prolonged retention release profile, while kept similar size distribution, encapsulation efficiency, low cytotoxicity and hemolysis comparing with NL. Confocal laser scanning microscopy and flow cytometry experiments confirmed the significantly higher cell uptake from AL and CL vesicles than the NL in mouse breast carcinoma and melanoma cells, human epithelial carcinoma and hepatoma cells. It was in accordance with our corresponding cellular mortality studies of DOX-loaded liposomes. The in vivo anti-tumor effect experiments from charged liposomes also presented much higher tumor inhibition effect (70% vs 45%, p < 0.05) than NL liposomes. This is the first time reporting anti-cancer effect from charged cholesterol liposome with/without PEGylation. It may give deeper understanding on the liposome formulation which is critical for liposome associated drug research and development.
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影响因子：
3
作者：
Addeo, Raffaele;Faiola, Vincenzo;Del Prete, Salvatore
通讯作者：
Del Prete, Salvatore
影响因子：
5.8
作者：
Gardikis, Konstantinos;Tsimplouli, Chrisiida;Demetzos, Costas
通讯作者：
Demetzos, Costas
影响因子：
3.4
作者：
Hafez, IM;Cullis, PR
通讯作者：
Cullis, PR
DOI：
10.1016/0005-2736(92)90086-2
发表时间：
1992-01-31
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
LEE, KD;HONG, K;PAPAHADJOPOULOS, D
通讯作者：
PAPAHADJOPOULOS, D
影响因子：
2.9
作者：
Miller, CR;Bondurant, B;O'Brien, DF
通讯作者：
O'Brien, DF