Abstract
Nucleoside analogues (NAs) are important agents in the treatment of hematological malignancies. They are prodrugs that require activation by phosphorylation. Their rapid catabolism, cell resistance and overdistribution in the body jeopardize nucleoside analogue chemotherapy. Accordingly, therapeutic doses of NAs are particularly high and regularly have to be increased, resulting in severe toxicity and narrow therapeutic index. The major challenge is to concentrate the drug at the tumour site, avoiding its distribution to normal tissues. New drug carriers and biomaterials are being developed to overcome some of these obstacles. This review highlights novel NA delivery systems and discusses new technologies that could improve NA cancer therapy.
Acknowledgements
We would like to acknowledge the publishers, Elsevier, Springer Netherlands and ACS, as well as the authors who granted their permission to use previously published scientific data and schematics as referenced in the figure captions.
Notes
VAN ROMPY AR, JOHANSSON M, KARLSSON A: Substrate specificity and phosphorylation of antiviral and anticancer nucleosides analogues by human deoxyribonucleoside kinanses and ribonucleoside kinases. Pharmacol. Ther. (2003) 100:119-139. VAN ROMPY AR, JOHANSSON M, KARLSSON A: Substrate specificity and phosphorylation of antiviral and anticancer nucleosides analogues by human deoxyribonucleoside kinanses and ribonucleoside kinases. Pharmacol. Ther. (2003) 100:119-139. MANTRIPRAGADA S: A lipid based depot (DepoFoam1 technology) for sustained release drug delivery. Prog. Lipid Res. (2002) 41: 392-406. MASSING U, FUXIUS S: Liposomal formulations of anticancer drugs: selectivity and effectiveness. Drug Resist. Update (2000) 3:171-177. MANTRIPRAGADA S: A lipid based depot (DepoFoam1 technology) for sustained release drug delivery. Prog. Lipid Res. (2002) 41: 392-406. MOOG R, BURGER AM, BRANDL M et al.: Change in pharmacokinetic and pharmacodynamic behaviour of gemcitabine in human tumor xenografts upon entrapment in vesicular phospholipid gels. Cancer Chemother. Pharmacol. (2002) 49:356-366. GARCIA O, BLANCO MD, MARTIN JA et al.: 5-Fluorouracil trapping in poly (2-hydroxyethyl methacrylate-co-acrylamide) hydrogels: in vitro drug delivery studies. Eur. Polym. J. (2000) 36:111-122. VINOGRADOV SV, ZEMAN AD, BATRAKOVA EV et al.: Polyplex nanogel formulations for drug delivery of cytotoxic nucleoside analogs. J. Control. Rel. (2005) 107:143-157. VINOGRADOV SV, KHOLI E, ZEMAN AD: Cross-linked polymeric nanogel formulations of 5′-triphosphates of nucleoside analogues: role of the cellular membrane in drug release. Mol. Pharm. (2005) 2(6):449-461. BLANCO MD, GÖMEZ C, OLMO R et al.: Chitosan microspheres in PLG films as devices for cytarabine release. Int. J. Pharm. (2000) 202:29-39. LAMPRECHT A, YAMAMOTO H, TAKEUCHI H, KAWASHIMA Y: Microsphere design for the colonic delivery of 5-fluorouracil. J. Control. Rel. (2003) 90:313-322. BOZKIR A, SAKA OM: Formulation and investigation of 5-FU nanoparticles with factorial design-based studies. Il Farmaco (2005) 60:840-846. BHADRA D, BHADRA S, JAIN S, JAIN NK: A PEGylated dendritic nanoparticulate carrier of fluorouracil. Int. J. Pharm. (2003) 257:111-124. JIE P, VENKATRAMAN SS, MIN F, FREDDY BY, HUAT GL: Micelle-like nanoparticles of star-branched PEO-PLA copolymers as chemotherapeutic carrier. J. Control. Rel. (2005) 110:20-33.
![Sample our Bioscience journals, sign in here to start your access, Latest two full volumes FREE to you for 14 days]({"type":"image" , "src" : "/sda/5925/TOC-Subject-Sample-2021-Bioscience.jpg"})