title: 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.affiliation: Università degli Studi di Torino, Facoltà di Farmacia, Dipartimento di Scienza e Tecnologia del Farmaco, Via P. Giuria 9, 10125 Torino, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Stella
authors.forename: Silvia
authors.initials: S
authors.lastname: Arpicco
authors.forename: Flavio
authors.initials: F
authors.lastname: Rocco
authors.forename: Véronique
authors.initials: V
authors.lastname: Marsaud
authors.forename: Jack-Michel
authors.initials: JM
authors.lastname: Renoir
authors.forename: Luigi
authors.initials: L
authors.lastname: Cattel
authors.forename: Patrick
authors.initials: P
authors.lastname: Couvreur
mesh_terms: 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
chemical_list: 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