Delivery of fluorescent-labeled cyclodextrin by liposomes: role of transferrin modification and phosphatidylcholine composition

被引:7
作者
Chen, Jun [1 ,2 ]
Yao, Junhong [2 ]
Mae, Zhuyue [2 ]
Peng, Pei [1 ]
Luz, Shanshan [2 ]
Hue, Yudong [2 ]
Xu, Fei [2 ]
Yang, Yang [1 ]
Yang, Xixiong [1 ]
机构
[1] Jingchu Univ Technol, Hubei Collaborat Innovat Ctr Targeted Antitumor D, 33 Xiangshan Rd, Jingmen 448000, Peoples R China
[2] Nanjing Univ Chinese Med, Sch Pharm, Pharmaceut Res Lab, Nanjing, Jiangsu, Peoples R China
关键词
Cellular uptake; hydroxypropyl-beta-cyclodextrin; liposomes; phosphatidylcholine; stability; transferrin modification; DRUG-DELIVERY; IN-VITRO; BETA-CYCLODEXTRIN; LIPID-COMPOSITION; PEGYLATED LIPOSOMES; ANTITUMOR-ACTIVITY; SYSTEMS; COMPLEXES; TUMOR; PHARMACOKINETICS;
D O I
10.3109/08982104.2016.1140184
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Drug-in-CD-in-liposome (DCL) systems which encapsulate the drug/CD inclusion complexes into inner aqueous phase of liposomes have been applied as a novel strategy to improve efficacy of lipophilic antitumor drugs. The aim of this work was to assess the role of transferrin (Tf) modification and phosphatidylcholine (PC) composition on the properties of liposomes containing hydroxypropyl-p-cyclodextrin (HP-beta-CD). Fluorescence dye, FITC, was conjugated with HP-beta-CD to facilitate the analysis. The resulting FITC-HP-beta-CD was further encapsulated into liposomes and then the liposomes were modified with Tf. The FITC-HP-beta-CD-loaded liposomes with different PC compositions were compared in terms of particle size, zeta potential, FITC content, FITC-HP-beta-CD leakage, phase transition temperature (T-m) and cellular uptake. The apparent partition coefficient values of different PCs were also determined. Compared to PEGylated liposomes, FITC-HP-beta-CD-loaded liposomes modified with Tf had been proved to significantly increase vesicle stability and specific cellular uptake. Moreover, PC composition affected the properties of liposomes. Soybean phosphatidylcholine (SPC) liposomes modified with Tf were found to be more easily internalized into tumor cells than 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) and hydrogenated soybean phosphatidylcholine (HSPC) while Tf density on the liposomal surface was similar. And the lipophilicity of SPC was found to be much higher than DPPC and HSPC. Collectively, by the optimization of PC composition, the development of DCL modified with Tf might represent a potential strategy for the antitumor application of lipophilic drugs.
引用
收藏
页码:21 / 31
页数:11
相关论文
共 40 条
[1]   Liposomal drug delivery systems: From concept to clinical applications [J].
Allen, Theresa M. ;
Cullis, Pieter R. .
ADVANCED DRUG DELIVERY REVIEWS, 2013, 65 (01) :36-48
[2]   The effect of different lipid components on the in vitro stability and release kinetics of liposome formulations [J].
Anderson, M ;
Omri, A .
DRUG DELIVERY, 2004, 11 (01) :33-39
[3]   Kinetics of cholesterol extraction from lipid membranes by methyl-β-cyclodextrin -: A surface plasmon resonance approach [J].
Besenicar, Mojca Podlesnik ;
Bavdek, Andrej ;
Kladnik, Ales ;
Macek, Peter ;
Anderluh, Gregor .
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 2008, 1778 (01) :175-184
[4]   Clinical development of liposome-based drugs: formulation, characterization, and therapeutic efficacy [J].
Chang, Hsin-I ;
Yeh, Ming-Kung .
INTERNATIONAL JOURNAL OF NANOMEDICINE, 2012, 7 :49-60
[5]   Lactone stability and tissue distribution of free and liposomal encapsulated 9-nitrocamptothecin in rats following intravenous injection [J].
Chen, Jun ;
Cai, Baochang ;
Ping, Qineng ;
Liu, Minling ;
Guo, Jianxin .
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY, 2008, 34 (08) :853-859
[6]   Characterization of 9-nitrocamptothecin-in-cyclodextrin-in-liposomes modified with transferrin for the treating of tumor [J].
Chen, Jun ;
Lu, Shanshan ;
Gu, Wei ;
Peng, Pei ;
Dong, Jie ;
Xu, Fei ;
Yang, Xueqin ;
Xiong, Zheyun ;
Yang, Xixiong .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2015, 490 (1-2) :219-228
[7]   Drug-in-cyclodextrin-inliposomes: a promising delivery system for hydrophobic drugs [J].
Chen, Jun ;
Lu, Wen-Li ;
Gu, Wei ;
Lu, Shan-Shan ;
Chen, Zhi-Peng ;
Cai, Bao-Chang ;
Yang, Xi-Xiong .
EXPERT OPINION ON DRUG DELIVERY, 2014, 11 (04) :565-577
[8]   Influence of lipid composition on the phase transition temperature of liposomes composed of both DPPC and HSPC [J].
Chen, Jun ;
Cheng, Dong ;
Li, Jun ;
Wang, Yong ;
Guo, Jian-xin ;
Chen, Zhi-peng ;
Cai, Bao-chang ;
Yang, Tao .
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY, 2013, 39 (02) :197-204
[9]  
Chen J, 2010, DRUG DEV IND PHARM, V36, P245, DOI [10.3109/03639040903099736, 10.1080/03639040903099736]
[10]   In vitro and in vivo Antitumor Activity of Doxorubicin-Loaded Alginic-Acid-Based Nanoparticles [J].
Cheng, Yuan ;
Yu, Shuling ;
Wang, Jingjing ;
Qian, Hanqing ;
Wu, Wei ;
Jiang, Xiqun .
MACROMOLECULAR BIOSCIENCE, 2012, 12 (10) :1326-1335