Encapsulation of gemcitabine lipophilic derivatives into polycyanoacrylate nanospheres and nanocapsules

The aim of this study was to develop both a physical and a chemical protection of the anticancer drug gemcitabine, which suffers from a rapid plasmatic metabolization. For this purpose, we used a series of lipophilic derivatives of gemcitabine in which an acyl chain is covalently coupled to the 4-am...

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Bibliographic Details
Published in:International journal of pharmaceutics 2007-11, Vol.344 (1), p.71-77
Main Authors: Stella, Barbara, Arpicco, Silvia, Rocco, Flavio, Marsaud, Véronique, Renoir, Jack-Michel, Cattel, Luigi, Couvreur, Patrick
Format: Article
Language:English
Subjects:
Antimetabolites, Antineoplastic - chemistry
Antimetabolites, Antineoplastic - pharmacology
Biological and medical sciences
Calorimetry, Differential Scanning
Cell Line, Tumor
Cyanoacrylates
Cytotoxicity
Deoxycytidine - analogs & derivatives
Deoxycytidine - chemistry
Deoxycytidine - pharmacology
Drug Compounding
Drug Delivery Systems
Gemcitabine
General pharmacology
Humans
Medical sciences
Nanocapsules
Nanospheres
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Polycyanoacrylate
Polymers
Prodrugs - chemistry
Structure-Activity Relationship
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Summary:The aim of this study was to develop both a physical and a chemical protection of the anticancer drug gemcitabine, which suffers from a rapid plasmatic metabolization. For this purpose, we used a series of lipophilic derivatives of gemcitabine in which an acyl chain is covalently coupled to the 4-amino group of gemcitabine; moreover, a physical protection of the drug was attempted by incorporating these lipophilic derivatives into poly(H 2NPEGCA- co-HDCA) nanospheres and nanocapsules. Nanoparticles were prepared by nanoprecipitation of the poly(H 2NPEGCA- co-HDCA) copolymer and their size, zeta potential and encapsulation efficiency were further characterized. These results have been relied on lipophilicity and flexibility studies. Data showed that only the more lipophilic derivative, 4-( N)-stearoylgemcitabine, was incorporated with a high yield. Thus, 4-( N)-stearoylgemcitabine-containing nanospheres and nanocapsules were further analyzed by differential scanning calorimetry. Their cytotoxicity was tested on two human cancer cell lines and compared to that of gemcitabine and free 4-( N)-stearoylgemcitabine.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2007.06.006