Background: Gemcitabine is a deoxycytidine analogue that exhibits antitumoral activity against adenocarcinomas of the colon, lung and pancreas. After intravenous injection, gemcitabine is rapidly converted to the inactive metabolite 2'-deoxy-2,2'-difluorouridine by cytidine deaminase. Materials and Methods: To improve the pharmacokinetic behavior and the antitumor activity of the drug, the gemcitabine prodrug, 4-(N)-stearoylgemcitabine (C18gem) was incorporated in liposomes and both the pharmacokinetic and the in vivo activity of this formulation intravenously or peritumorally administered in nude female CR1:Nu/Nu(CD-1)BR mice grafted with HT-29 and KB 396p cells were studied. Results: The C18gem-liposomes showed both higher plasma half life and tumor regression than control and gemcitabine. Conclusion: The incorporation of C18gem-prodrug in liposomes increased the plasma half life of the drug resulting in increased accumulation in the tumor cells and a higher level of antitumoral efficacy. The results obtained with different tumors sensitive to gemcitabine support the efficacy of this proposed drug delivery system.

Antitumor activity and pharmacokinetics of liposomes containing lipophilic gemcitabine prodrugs

BRUSA, Paola;IMMORDINO, Maria Laura;ROCCO, Flavio;CATTEL, Luigi
2007-01-01

Abstract

Background: Gemcitabine is a deoxycytidine analogue that exhibits antitumoral activity against adenocarcinomas of the colon, lung and pancreas. After intravenous injection, gemcitabine is rapidly converted to the inactive metabolite 2'-deoxy-2,2'-difluorouridine by cytidine deaminase. Materials and Methods: To improve the pharmacokinetic behavior and the antitumor activity of the drug, the gemcitabine prodrug, 4-(N)-stearoylgemcitabine (C18gem) was incorporated in liposomes and both the pharmacokinetic and the in vivo activity of this formulation intravenously or peritumorally administered in nude female CR1:Nu/Nu(CD-1)BR mice grafted with HT-29 and KB 396p cells were studied. Results: The C18gem-liposomes showed both higher plasma half life and tumor regression than control and gemcitabine. Conclusion: The incorporation of C18gem-prodrug in liposomes increased the plasma half life of the drug resulting in increased accumulation in the tumor cells and a higher level of antitumoral efficacy. The results obtained with different tumors sensitive to gemcitabine support the efficacy of this proposed drug delivery system.
2007
27
195
199
Gemcitabine; gemcitabine prodrugs; liposomes; in vivo activity
BRUSA P; IMMORDINO ML; ROCCO F; CATTEL L
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/27413
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