Encapsulation of gemcitabine lipophilic derivatives into polycyanoacrylate nanospheres and nanocapsules.

Abstract

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(2)NPEGCA-co-HDCA) nanospheres and nanocapsules. Nanoparticles were prepared by nanoprecipitation of the poly(H(2)NPEGCA-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.

• Authors: Barbara Stella, Silvia Arpicco, Flavio Rocco, Véronique Marsaud, Jack-Michel Renoir, Luigi Cattel, Patrick Couvreur
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 344 Issue 1-2 Pg. 71-7 (Nov 01 2007) ISSN: 0378-5173 [Print] Netherlands
• PMID: 17651931 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 4-(N)-stearoylgemcitabine
• Antimetabolites, Antineoplastic
• Cyanoacrylates
• Nanocapsules
• Polymers
• Prodrugs
• poly(aminopoly(ethylene glycol) cyanoacrylate-co-hexadecyl cyanoacrylate)
• Deoxycytidine
• Gemcitabine

Topics

• Antimetabolites, Antineoplastic (chemistry, pharmacology)
• Calorimetry, Differential Scanning
• Cell Line, Tumor
• Cyanoacrylates
• Deoxycytidine (analogs & derivatives, chemistry, pharmacology)
• Drug Compounding
• Drug Delivery Systems
• Humans
• Nanocapsules
• Nanospheres
• Polymers
• Prodrugs (chemistry)
• Structure-Activity Relationship
• Gemcitabine