X-ray diffraction from paclitaxel-loaded zwitterionic and cationic model membranes

被引:15
作者
Cavalcanti, Leide P.
Konovalov, Oleg
Haas, Heinrich
机构
[1] European Synchrotron Radiat Facil, F-38043 Grenoble, France
[2] Formulat Dev, Medigence AG, D-82152 Martinsried, Germany
关键词
paclitaxel; lipid membranes; cationic liposomes; targeted drug delivery; nanoparticles; cancer; x-ray diffraction;
D O I
10.1016/j.chemphyslip.2007.06.219
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
We studied the incorporation of the hydrophobic anticancer drug paclitaxel (PXL), into a variety of lipid matrices by X-ray diffraction (XRD) measurements. Liposome suspensions from cationic and zwitterionic lipids, containing different molar fractions of paclitaxel were made and deposited on planar glass substrates. After drying at controlled relative humidity, aligned multilayer stacks were obtained. The structure perpendicular to the substrate plane was investigated by X-ray diffraction measurements. Bragg peaks to several orders were detected, indicative of well-ordered multilamellar lipid layers. The drug induced a modification of the bilayer spacing, which was the characteristic for a given type of lipid matrix. With an excess of the drug, Bragg peaks of drug crystals could be observed. The results provide insight into the solubility of paclitaxel in the different lipid membranes. Astructural model of the organization of the drug in the membrane was discussed. (C) 2007 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:58 / 65
页数:8
相关论文
共 33 条
[21]  
SEYDEL JK, 2002, METHODS PRINCIPLES M, V15
[22]   NOVEL TAXOL FORMULATIONS - PREPARATION AND CHARACTERIZATION OF TAXOL-CONTAINING LIPOSOMES [J].
SHARMA, A ;
STRAUBINGER, RM .
PHARMACEUTICAL RESEARCH, 1994, 11 (06) :889-896
[23]   Paclitaxel and its formulations [J].
Singla, AK ;
Garg, A ;
Aggarwal, D .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2002, 235 (1-2) :179-192
[24]   Troika II: a versatile beamline for the study of liquid and solid interfaces [J].
Smilgies, DM ;
Boudet, N ;
Struth, B ;
Konovalov, O .
JOURNAL OF SYNCHROTRON RADIATION, 2005, 12 :329-339
[25]   Preparation and characterization of taxane-containing liposomes [J].
Straubinger, RM ;
Balasubramanian, SV .
LIPOSOMES, PT E, 2005, 391 :97-117
[26]   Cationic liposomes target angiogenic endothelial cells in tumors and chronic inflammation in mice [J].
Thurston, G ;
McLean, JW ;
Rizen, M ;
Baluk, P ;
Haskell, A ;
Murphy, TJ ;
Hanahan, D ;
McDonald, DM .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 101 (07) :1401-1413
[27]   Recent advances with liposomes as pharmaceutical carriers [J].
Torchilin, VP .
NATURE REVIEWS DRUG DISCOVERY, 2005, 4 (02) :145-160
[28]   Role of formulation vehicles in taxane pharmacology [J].
van Zuylen, L ;
Verweij, J ;
Sparreboom, A .
INVESTIGATIONAL NEW DRUGS, 2001, 19 (02) :125-141
[29]   Paclitaxel partitioning into lipid bilayers [J].
Wenk, MR ;
Fahr, A ;
Reszka, R ;
Seelig, J .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1996, 85 (02) :228-231
[30]   STRUCTURE OF A FLUID DIOLEOYLPHOSPHATIDYLCHOLINE BILAYER DETERMINED BY JOINT REFINEMENT OF X-RAY AND NEUTRON-DIFFRACTION DATA .2. DISTRIBUTION AND PACKING OF TERMINAL METHYL-GROUPS [J].
WIENER, MC ;
WHITE, SH .
BIOPHYSICAL JOURNAL, 1992, 61 (02) :428-433