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1.
Chem Pharm Bull (Tokyo) ; 55(7): 1006-10, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17603190

ABSTRACT

Increase of lipophilicity of cationic doxorubicin (DOX) by its association with a fatty acid ion is of interest for pharmaceutical formulations and could have an impact on the drug delivery into cancer cells. On the basis of spectroscopic analysis of intrinsic DOX fluorescence, this study provides an experimental evidence of DOX-oleate interactions as function of ion/drug molar ratio (R) and pH. An electrostatic attraction to oleates is dominant for the cationic form of DOX (pH 6.5) and a hydrophobic interaction is characteristic of the molecular form of DOX (pH 8.6). A high content of sodium oleate vesicles ([oleate]>/=0.2 mM, R>/=20) limits the electrostatic and hydrophobic interactions at pH 6.5 while favoring the hydrophobic interactions at pH 8.6. The influence of these interactions on the lipophilicity of the cationic form of DOX is analyzed by measuring the apparent partition coefficient (aqueous buffer pH 6.5/methylene chloride). The results show a lipophilicity gain for the cationic form of DOX in presence of 10 : 1 ion/drug molar ratio, while no lipophilicity increase is observed at 50 : 1 molar ratio.


Subject(s)
Doxorubicin/chemistry , Oleic Acid/chemistry , Antibiotics, Antineoplastic/chemistry , Cations , Hydrogen-Ion Concentration , Lipids/chemistry , Models, Biological , Molecular Structure , Solubility , Spectrometry, Fluorescence , Water/chemistry
2.
Eur J Pharm Biopharm ; 67(1): 31-8, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17289360

ABSTRACT

This work describes a method for preparation of sub-micron poly(d,l-lactide-co-glycolide) (PLGA) particles loaded with magnetite/maghemite nanoparticles to be used as magnetically-controlled drug delivery systems. The methodology of simple emulsion/evaporation technique has been optimized to provide greater iron oxide loading rates. The surface of iron oxide nanoparticles was coated with oleic acid (OA) for better compatibility with organic phase containing the polymer. To increase their loading into polymeric sub-micron particles, we added dried iron oxide nanoparticles in variable ferrite/polymer ratio of 1:1; 1:1.5 and 1:2 w/w. Composition and surface properties of obtained composite sub-micron particles have been studied in comparison with those of ferrite-free PLGA sub-micron particles. Presence of magnetite/maghemite was qualitatively confirmed by characteristic bands in the FT-IR spectra of composite sub-micron particles. Quantification of the incorporated iron was achieved by AAS. The highest incorporation rates of ferrite (up to 13.5% w/w) were observed with initial ferrite/polymer ratio of 1:1 w/w. TEM images indicate that the composite sub-micron particles are nearly spherical. According to laser granulometry data, average hydrodynamic diameter of the composite sub-micron particles is close to 280nm, independently of ferrite presence. Electrophoretic properties (zeta potential) were very similar for both composite and ferrite-free PLGA sub-micron particles, thus indicating that the polymeric coating should mask the surface of ferrite nanoparticles buried inside. Finally, composite sub-micron particles exhibit superparamagnetic property.


Subject(s)
Ferric Compounds/chemistry , Nanoparticles/chemistry , Chemical Phenomena , Chemistry, Physical , Drug Compounding , Electrochemistry , Hydrogen-Ion Concentration , Lactic Acid , Microscopy, Electron, Transmission , Oleic Acid/chemistry , Particle Size , Polyglycolic Acid , Polylactic Acid-Polyglycolic Acid Copolymer , Polymers , Spectroscopy, Fourier Transform Infrared , Surface Properties
3.
Int J Nanomedicine ; 2(4): 541-50, 2007.
Article in English | MEDLINE | ID: mdl-18203422

ABSTRACT

During the last decade, the application of nanotechnologies for anticancer drug delivery has been extensively explored, hoping to improve the efficacy and to reduce side effects of chemotherapy. The present review is dedicated to a certain kind of anticancer drug nanovectors developed to target tumors with the help of an external magnetic field. More particularly, this work treats anticancer drug nanoformulations based on superparamagnetic iron oxide nanoparticles coated with biocompatible polymers. The major purpose is to focus on the specific requirements and technological difficulties related to controlled delivery of antitumoral agents. We attempt to state the problem and its possible perspectives by considering the three major constituents of the magnetic therapeutic vectors: iron oxide nanoparticles, polymeric coating and anticancer drug.


Subject(s)
Antineoplastic Agents/administration & dosage , Antineoplastic Agents/chemistry , Drug Carriers/chemistry , Iron/chemistry , Nanomedicine/methods , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Oxides/chemistry , Dextrans , Ferrosoferric Oxide , Magnetite Nanoparticles
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