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-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.
Stella
Barbara
B
Università degli Studi di Torino, Facoltà di Farmacia, Dipartimento di Scienza e Tecnologia del Farmaco, Via P. Giuria 9, 10125 Torino, Italy.
Arpicco
Silvia
S
Rocco
Flavio
F
Marsaud
Véronique
V
Renoir
Jack-Michel
JM
Cattel
Luigi
L
Couvreur
Patrick
P
D000964:Antimetabolites, Antineoplastic / Q000737:chemistry* / Q000494:pharmacology; D002152:Calorimetry, Differential Scanning; D045744:Cell Line, Tumor; D003487:Cyanoacrylates; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004339:Drug Compounding; D016503:Drug Delivery Systems; D006801:Humans; D053769:Nanocapsules; D054118:Nanospheres; D011108:Polymers; D011355:Prodrugs / Q000737:chemistry; D013329:Structure-Activity Relationship; D000093542:Gemcitabine
C525761:4-(N)-stearoylgemcitabine; D000964:Antimetabolites, Antineoplastic; D003487:Cyanoacrylates; D053769:Nanocapsules; D011108:Polymers; D011355:Prodrugs; C519809:poly(aminopoly(ethylene glycol) cyanoacrylate-co-hexadecyl cyanoacrylate); D003841:Deoxycytidine; D000093542:Gemcitabine