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.
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.
Authors: Brian R Sloat; Michael A Sandoval; Dong Li; Woon-Gye Chung; Dharmika S P Lansakara-P; Philip J Proteau; Kaoru Kiguchi; John DiGiovanni; Zhengrong Cui Journal: Int J Pharm Date: 2011-03-01 Impact factor: 5.875
Authors: Eric M Mastria; Mingnan Chen; Jonathan R McDaniel; Xinghai Li; Jinho Hyun; Mark W Dewhirst; Ashutosh Chilkoti Journal: J Control Release Date: 2015-01-28 Impact factor: 9.776
Authors: Jayanta Bhattacharyya; Isaac Weitzhandler; Shihan Bryan Ho; Jonathan R McDaniel; Xinghai Li; Lei Tang; Jinyao Liu; Mark Dewhirst; Ashutosh Chilkoti Journal: Adv Funct Mater Date: 2017-02-07 Impact factor: 18.808