Novel Approaches to Deliver Gemcitabine to Cancers
L. Harivardhan Reddy and Patrick Couvreur
Affiliation: Univ. Paris-Sud XI, Faculte de Pharmacie, UMR CNRS 8612, 92296 Chatenay-Malabry Cedex, France.
The objective of this review is to discuss the strategies adopted to improve the delivery of gemcitabine to tumors. Concomitant research in this area has implemented a wide variety of approaches such as, aerosolized formulations, prodrug conjugates, liposomes, nanoparticles and beads. Some of these strategies were also aimed at overcoming the rapid metabolization and drug resistance associated with gemcitabine. Aerosolized formulations were employed to treat the local tumors, while other approaches were aimed at the systemic therapy of cancers. The liposomal formulations considerably increased the half-life and the area under the curve (AUC) of gemcitabine, and simultaneously caused a marked improvement in the anticancer activity against experimental solid tumors developed orthotopically or at subcutaneous site. Alternatively, the prodrug conjugates of gemcitabine displayed considerable activity in vivo against various tumors. Especially, in the case of leukemia in which gemcitabine was demonstrated to be inactive, the lipidic conjugates displayed marked efficiency following systemic and oral administration. These conjugates induced greater apoptosis and also caused resistance reversal in the resistant leukemia types. Altogether, the delivery strategies adopted for gemcitabine led to a considerable improvement in the treatment of cancers at the preclinical stage, and some of them are potential candidates for clinical trials.
Keywords: Gemcitabine, cancer, drug delivery, nanoparticles, liposomes, lipid prodrugs, resistant cancer
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