Innovations and opportunities to improve conventional (deoxy)nucleoside and fluoropyrimidine analogs in cancer

Current Medicinal Chemistry

Volumn 16, Issue 35, 2009, Pages 4632-4643

  Adema, A D ^a   Bijnsdorp, I V ^a   Sandvold, M L ^b   Verheul, H M ^a   Peters, G J ^a  

^a VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^b Clavis Pharma ASA   (Norway)

Author keywords

Deoxynucleoside analogs; Drug targeting; Fluoropyrimidine analogs; Lipophilic prodrugs; Liposomes; Nanoparticles

Indexed keywords

5 (2 BROMOVINYL) 2' DEOXYURIDINE; 5 CHLORO 2,4 DIHYDROXYPYRIDINE PLUS OXONATE POTASSIUM PLUS TEGAFUR; ALPHA INTERFERON; CAMPTOTHECIN; CAPECITABINE; CLORETAZINE; CP 4055; CYTARABINE; CYTARABINE DERIVATIVE; CYTOTOXIC AGENT; DAUNORUBICIN; DEOXYCYTIDINE; DEOXYNUCLEOSIDE DERIVATIVE; DOXORUBICIN; DRUG CARRIER; FLUOROPYRIMIDINE DERIVATIVE; FLUOROURACIL; GEMCITABINE; IDARUBICIN; IMATINIB; IRINOTECAN; LIPOSOME; METHOTREXATE; NANOPARTICLE; NUCLEOSIDE ANALOG; PACLITAXEL; PYRIMIDINE DERIVATIVE; TOPOTECAN; TROXACITABINE; UNCLASSIFIED DRUG; UNINDEXED DRUG; YKN 01;

ACUTE GRANULOCYTIC LEUKEMIA; ANTINEOPLASTIC ACTIVITY; ANTIVIRAL ACTIVITY; BREAST CANCER; CANCER INHIBITION; CHEMICAL MODIFICATION; CHRONIC MYELOID LEUKEMIA; CLINICAL TRIAL; COLORECTAL CANCER; DIARRHEA; DRUG BINDING SITE; DRUG DELIVERY SYSTEM; DRUG MECHANISM; DRUG STABILITY; DRUG STRUCTURE; DRUG TARGETING; DRUG TRANSPORT; ENZYME PHOSPHORYLATION; HAND FOOT SYNDROME; HEAD AND NECK CANCER; HUMAN; HYDROPHILICITY; HYDROPHOBICITY; KAPOSI SARCOMA; LIPOPHILICITY; LIVER TOXICITY; MALIGNANT NEOPLASTIC DISEASE; NANOENCAPSULATION; NONHUMAN; OVARY CANCER; REVIEW; SOLID TUMOR; STRUCTURE ANALYSIS;

ANTINEOPLASTIC AGENTS; DEOXYRIBONUCLEOSIDES; DRUG CARRIERS; LIPOSOMES; NANOPARTICLES; NEOPLASMS; PYRIMIDINES;

EID: 72449181468     PISSN: 09298673     EISSN: None     Source Type: Journal    
DOI: 10.2174/092986709789878229     Document Type: Review

References (102)

1. Bergman, A.M.; Pinedo, H.M.; Peters, G.J. Determinants of resistance to 2′,2′-difluorodeoxycytidine (gemcitabine). Drug Resist. Update, 2002, 5, 19-33.
2. Kroep, J.R.; Loves, W.J.; van der Wilt, C.L.; Alvarez, E.; Talianidis, I.; Boven, E.; Braakhuis, B.J.; van Groeningen, C.J.; Pinedo, H.M.; Peters, G.J. Pretreatment deoxycytidine kinase levels predict in vivo gemcitabine sensitivity. Mol. Cancer Ther., 2002, 1, 371-376
3. Hubeek I., Kaspers G.J., Ossenkoppele G.J., Peters G.J. In Cancer Drug Discovery and Development: Deoxynucleoside Analogs in Cancer Therapy; Peters G.J., Ed.; Humana Press inc.: Totowa, 2006; pp. 119-152
4. Peters G.J., Jansen G. In Principles of Antineoplastic Drug Development and Pharmacology; Schilsky R.L., Milano G.A., Ratain M.J., Ed.; Marcel Dekker, Inc: New York, 1996; pp. 543-585
5. Engelman, J.A.; Janne, P.A. Mechanisms of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in nonsmall cell lung cancer. Clin. Cancer Res., 2008, 14, 2895-2899
6. Bergman, A.M.; Kuiper, C.M.; Voorn, D.A.; Comijn, E.M.; Myhren, F.; Sandvold, M.L.; Hendriks, H.R.; Peters, G.J. Antiproliferative activity and mechanism of action of fatty acid derivatives of arabinofuranosylcytosine in leukemia and solid tumor cell lines. Biochem. Pharmacol., 2004, 67, 503-511 (Pubitemid 38232890)
7. Adams, D.J.; Sandvold, M.L.; Myhren, F.; Jacobsen, T.F.; Giles, F.; Rizzieri, D.A. Anti proliferative activity of ELACYT (CP-4055) in combination with cloretazine (VNP40101M), idarubicin, gemcitabine, irinotecan and topotecan in human leukemia and lymphoma cells. Leuk. Lymphoma, 2008, 49, 786-797
8. Breistol, K.; Balzarini, J.; Sandvold, M.L.; Myhren, F.; Martinsen, M.; De Clercq, E.; Fodstad, O. Antitumor activity of P-4055 (elaidic acid-cytarabine) compared to cytarabine in metastatic and s.c. human tumor xenograft models. Cancer Res., 1999, 59, 2944-2949 (Pubitemid 29283136)
9. Dueland, S.; Aamdal, S.; Lind, M.J.; Thomas, H.; Sandvold, M.L.; Gaullier, J.M.; Rasch, W. Intravenous administration of CP-4055 (ELACYT™) in patients with solid tumours. A phase I study. Acta Oncol., 2008, 48, 1-9.
10. Serova, M.; Galmarini, C.M.; Ghoul, A.; Benhadji, K.; Green, S.R.; Chiao, J.; Faivre, S.; Cvitkovic, E.; Le Tourneau, C.; Calvo, F.; Raymond, E. Antiproliferative effects of sapacitabine (CYC682), a novel 2'-deoxycytidine- derivative, in human cancer cells. Br. J. Cancer, 2007, 97, 628-636 (Pubitemid 47339878)
11. Gilbert, J.; Carducci, M.A.; Baker, S.D.; Dees, E.C.; Donehower, R. A Phase I study of the oral antimetabolite, CS-682, administered once daily 5 days per week in patients with refractory solid tumor malignancies. Invest. New Drugs, 2006, 24, 499-508. (Pubitemid 44273025)
12. Delaunoit, T.; Burch, P.A.; Reid, J.M.; Camoriano, J.K.; Kobayash, T.; Braich, T.A.; Kaur, J.S.; Rubin, J.; Erlichman, C. A phase I clinical and pharmacokinetic study of CS-682 administered orally in advanced malignant solid tumors. Invest. New Drugs, 2006, 24, 327-333
13. Schwendener, R.A.; Schott, H. Treatment of L1210 murine leukemia with liposome-incorporated N4-hexadecyl-1-beta-Darabinofuranosyl cytosine. Int. J. Cancer, 1992, 51, 466-469
14. Schwendener, R.A.; Friedl, K.; Depenbrock, H.; Schott, H.; Hanauske, A.R. In vitro activity of liposomal N4octadecyl-1-beta- D-arabinofuranosylcytosine (NOAC), a new lipophilic derivative of 1-beta-D-arabinofuranocylcytosine on biopsized clonogenic human tumor cells and hematopoietic precursor cells. Invest. New Drugs, 2001, 19, 203-210
15. Koller-Lucae, S.K.; Suter, M.J.; Rentsch, K.M.; Schott, H.; Schwendener, R.A. Metabolism of the new liposomal anticancer drug N4-octadecyl-1-beta-D- arabinofuranosylcytosine in mice. Drug Metab. Dispos., 1999, 27, 342-350
16. Schwendener, R.A.; Horber, D.H.; Ottiger, C.; Schott, H. Preclinical Properties of N-4-Hexadecyl- and N-4-Octadecyl-1-β-D- Arabinofuranosylcytosine in Liposomal Preparations. J. Liposome Res., 1995, 5, 27-47.
17. Horber, D.H.; von Ballmoos P.; Schott, H.; Schwendener, R.A. Cell cycle-dependent cytotoxicity and induction of apoptosis by liposomal N4-hexadecyl-1-beta-D-arabinofuranosylcytosine. Br. J. Cancer, 1995, 72, 1067-1073
18. Horber, D.H.; Cattaneo-Pangrazzi, R.M.; von Ballmoos, P.; Schott, H.; Ludwig, P.S.; Eriksson, S.; Fichtner, I.; Schwendener, R.A. Cytotoxicity, cell-cycle perturbations and apoptosis in human tumor cells by lipophilic N4-alkyl-1-beta-D-arabinofuranosylcytosine derivatives and the new heteronucleoside phosphate dimer arabinocytidylyl-(5′-->5′)-N4- octadecyl-1-beta-D-arabinofuranosylcytosine. J. Cancer Res. Clin. Oncol., 2000, 126, 311-319
19. Radi, M.; Adema, A.D.; Daft, J.R.; Cho, J.H.; Hoebe, E.K.; Alexander, L.E.; Peters, G.J.; Chu, C.K. In vitro optimization of non-small cell lung cancer activity with troxacitabine, L-1,3-dioxolane-cytidine, prodrugs. J. Med. Chem., 2007, 50, 2249-2253
20. Adema, A.D.; Radi, M.; Daft, J.; Narayanasamy, J.; Hoebe, E.K.; Alexander, L.E.; Chu, C.K.; Peters, G.J. Troxacitabine prodrugs for pancreatic cancer. Nucleosides Nucleotides Nucleic Acids, 2007, 26, 1073-1077
21. Miwa, M.; Ura, M.; Nishida, M.; Sawada, N.; Ishikawa, T.; Mori, K.; Shimma, N.; Umeda, I.; Ishitsuka, H. Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue. Eur. J. Cancer, 1998, 34, 1274-1281 (Pubitemid 28342121)
22. Ishikawa, T.; Utoh, M.; Sawada, N.; Nishida, M.; Fukase, Y.; Sekiguchi, F.; Ishitsuka, H. Tumor selective delivery of 5- fluorouracil by capecitabine, a new oral fluoropyrimidine carbamate, in human cancer xenografts. Biochem. Pharmacol., 1998, 55, 1091-1097 (Pubitemid 28167730)
23. Ishikawa, T.; Sekiguchi, F.; Fukase, Y.; Sawada, N.; Ishitsuka, H. Positive correlation between the efficacy of capecitabine and doxifluridine and the ratio of thymidine phosphorylase to dihydropyrimidine dehydrogenase activities in tumors in human cancer xenografts. Cancer Res., 1998, 58, 685-690 (Pubitemid 28099478)
24. Schoffski, P. The modulated oral fluoropyrimidine prodrug S-1, and its use in gastrointestinal cancer and other solid tumors. Anticancer Drugs, 2004, 15, 85-106. (Pubitemid 38316741)
25. Alexander, R.L.; Greene, B.T.; Torti, S.V.; Kucera, G.L. A novel phospholipid gemcitabine conjugate is able to bypass three drug-resistance mechanisms. Cancer Chemother. Pharmacol., 2005, 56, 15-21.
26. Saneyoshi, M.; Morozumi, M.; Kodama, K.; Machida, H.; Kuninaka, A.; Yoshino, H. Synthetic nucleosides and nucleotides. XVI. Synthesis and biological evaluations of a series of 1-beta-D-arabinofuranosylcytosine 5′-alkyl or arylphosphates. Chem. Pharm. Bull. (Tokyo), 1980, 28, 2915-2923
27. Kodama, K.; Morozumi, M.; Saitoh, K.; Kuninaka, A.; Yoshino, H.; Saneyoshi, M. Antitumor activity and pharmacology of 1-beta-D- arabinofuranosylcytosine-5′-stearylphosphate: an orally active derivative of 1-beta-D-arabinofuranosylcytosine. Jpn. J. Cancer Res., 1989, 80, 679-685 (Pubitemid 20036009)
28. Mollee, P.; Arthur, C.; Hughes, T.; Januszewicz, H.; Grigg, A.; Bradstock, K.; Wolf, M.; Gibson, J.; Schwarer, A.P.; Spencer, A.; Browett, P.; Hawkins, T.; Seldon, M.; Herrmann, R.; Watson, A.; Seymour, J.F.; Martin, N.; Shina, S.; Low, C.; Wright, S.; Rodwell, R.; Coulston, J.; Morton, J.; Blacklock, H.; Taylor, D.; Taylor, K.M. Interferon-alpha-2b and oral cytarabine ocfosfate for newly diagnosed chronic myeloid leukaemia. Ann. Oncol., 2004, 15, 1810-1815
29. Rosti, G.; Bonifazi, F.; Trabacchi, E.; De Vivo A.; Bassi, S.; Martinelli, G.; Testoni, N.; Russo, D.; Baccarani, M. A phase II study of alpha-interferon and oral arabinosyl cytosine (YNK01) in chronic myeloid leukemia. Leukemia, 2003, 17, 554-559 (Pubitemid 36395649)
30. Maloisel, F.; Guerci, A.; Guyotat, D.; Ifrah, N.; Michallet, M.; Reiffers, J.; Tertain, G.; Blanc, M.; Bauduer, F.; Briere, J.; Abgrall, J.F.; Pegourie-Bandelier, B.; Solary, E.; Cambier, N.; Coso, D.; Vilque, J.P.; Delain, M.; Harousseau, J.L.; Rousselot, P.; Belhadj, K.; Morice, P.; Attal, J.; Chabin, M.; Chastang, C.; Guilhot, J.; Guilhot, F. Results of a phase II trial of a combination of oral cytarabine ocfosfate (YNK01) and interferon alpha-2b for the treatment of chronic myelogenous leukemia patients in chronic phase. Leukemia, 2002, 16, 573-580 (Pubitemid 34449736)
31. Boyer, S.H.; Sun, Z.; Jiang, H.; Esterbrook, J.; Gomez-Galeno, J.E.; Craigo, W.; Reddy, K.R.; Ugarkar, B.G.; MacKenna, D.A.; Erion, M.D. Synthesis and characterization of a novel liver-targeted prodrug of cytosine-1-beta-D- arabinofuranoside monophosphate for the treatment of hepatocellular carcinoma. J. Med. Chem., 2006, 49, 7711-7720
32. Meier, C.; Balzarini, J. Application of the cycloSal-prodrug approach for improving the biological potential of phosphorylated biomolecules. Antiviral. Res., 2006, 71, 282-292 (Pubitemid 44223763)
33. Jessen, H.J.; Balzarini, J.; Meier, C. Intracellular Trapping of cycloSal-Pronucleotides: modification of prodrugs with amino acid esters. J. Med. Chem., 2008, 51, 6592-6598
34. Gisch, N.; Balzarini, J.; Meier, C. Studies on Enzyme-Cleavable Dialkoxymethyl-cycloSaligenyl-2′,3′-dideoxy-2′, 3′-didehydrothymidine Monophosphates. J. Med. Chem., 2008, 51, 6752-6760.
35. Cahard, D.; McGuigan, C.; Balzarini, J. Aryloxy phosphoramidate triesters as pro-tides. Mini Rev. Med. Chem., 2004, 4, 371-381
36. McGuigan, C.; Pathirana, R.N.; Balzarini, J.; De Clercq E. Intracellular delivery of bioactive AZT nucleotides by aryl phosphate derivatives of AZT. J. Med. Chem., 1993, 36, 1048-1052 (Pubitemid 23143618)
37. McGuigan, C.; Cahard, D.; Sheeka, H.M.; De Clercq E.; Balzarini, J. Aryl phosphoramidate derivatives of d4T have improved anti-HIV efficacy in tissue culture and may act by the generation of a novel intracellular metabolite. J. Med. Chem., 1996, 39, 1748-1753 (Pubitemid 26124246)
38. Perrone, P.; Luoni, G.M.; Kelleher, M.R.; Daverio, F.; Angell, A.; Mulready, S.; Congiatu, C.; Rajyaguru, S.; Martin, J.A.; Leveque, V.; Le Pogam, S.; Najera, I.; Klumpp, K.; Smith, D.B.; McGuigan, C. Application of the phosphoramidate ProTide approach to 4′-azidouridine confers sub-micromolar potency versus hepatitis C virus on an inactive nucleoside. J. Med. Chem., 2007, 50, 1840-1849 (Pubitemid 46626594)
39. McGuigan, C.; Derudas, M.; Bugert, J.J.; Andrei, G.; Snoeck, R.; Balzarini, J. Successful kinase bypass with new acyclovir phosphoramidate prodrugs. Bioorg. Med. Chem. Lett., 2008, 18, 4364-4367
40. Tobias, S.C.; Borch, R.F. Synthesis and biological studies of novel nucleoside phosphoramidate prodrugs. J. Med. Chem., 2001, 44, 4475-4480 (Pubitemid 33131672)
41. Tobias, S.C.; Borch, R.F. Synthesis and biological evaluation of a cytarabine phosphoramidate prodrug. Mol. Pharm., 2004, 1, 112-116
42. De Clercq E. (E)-5-(2-bromovinyl)-2′-deoxyuridine (BVDU). Med. Res. Rev., 2005, 25, 1-20.
43. Li, Q.; Boyer, C.; Lee, J.Y.; Shepard, H.M. A novel approach to thymidylate synthase as a target for cancer chemotherapy. Mol. Pharmacol., 2001, 59, 446-452 (Pubitemid 32179922)
44. McGuigan, C.; Thiery, J.C.; Daverio, F.; Jiang, W.G.; Davies, G.; Mason, M. Anti-cancer ProTides: tuning the activity of BVDU phosphoramidates related to thymectacin. Bioorg. Med. Chem., 2005, 13, 3219-3227
45. Congiatu, C.; Brancale, A.; Mason, M.D.; Jiang, W.G.; McGuigan, C. Novel potential anticancer naphthyl phosphoramidates of BVdU: separation of diastereoisomers and assignment of the absolute configuration of the phosphorus center. J. Med. Chem., 2006, 49, 452-455 (Pubitemid 43157476)
46. Wu, W.; Sigmond, J.; Peters, G.J.; Borch, R.F. Synthesis and biological activity of a gemcitabine phosphoramidate prodrug. J. Med. Chem., 2007, 50, 3743-3746
47. Reiser, H.; Wang, J.; Chong, L.; Watkins, W.J.; Ray, A.S.; Shibata, R.; Birkus, G.; Cihlar, T.; Wu, S.; Li, B.; Liu, X.; Henne, I.N.; Wolfgang, G.H.; Desai, M.; Rhodes, G.R.; Fridland, A.; Lee, W.A.; Plunkett, W.; Vail, D.; Thamm, D.H.; Jeraj, R.; Tumas, D.B. GS-9219 - a novel acyclic nucleotide analogue with potent antineoplastic activity in dogs with spontaneous non-Hodgkin's lymphoma. Clin. Cancer Res., 2008, 14, 2824-2832
48. Saiko, P.; Horvath, Z.; Illmer, C.; Madlener, S.; Bauer, W.; Hoechtl, T.; Erlach, N.; Grusch, M.; Krupitza, G.; Mader, R.M.; Jaeger, W.; Schott, H.; Agarwal, R.P.; Fritzer-Szekeres, M.; Szekeres, T. Cytotoxic effects of novel amphiphilic dimers consisting of 5-fluorodeoxyuridine and arabinofuranosylcytosine in cross-resistant H9 human lymphoma cells. Leuk. Res., 2005, 29, 785-791 (Pubitemid 40779485)
49. Bijnsdorp, I.V.; Schwendener, R.A.; Schott, H.; Fichtner, I.; Smid, K.; Schott, S.; Laan, A.C.; Peters, G.J. In vivo and in vitro activity and mechanism of action of the multidrug cytarabine-L-glycerylyl-fluorodeoxyuridine. Nucleosides Nucleotides Nucleic Acids, 2007, 26, 1619-1624 (Pubitemid 350240793)
50. Cattaneo-Pangrazzi, R.M.; Schott, H.; Schwendener, R.A. The novel heterodinucleoside dimer 5-FdU-NOAC is a potent cytotoxic drug and a p53-independent inducer of apoptosis in the androgen-independent human prostate cancer cell lines PC-3 and DU-145. Prostate, 2000, 45, 8-18.
51. Cattaneo-Pangrazzi, R.M.; Schott, H.; Wunderli-Allenspach, H.; Rothen-Rutishauser, B.; Guenthert, M.; Schwendener, R.A. Cell-cycle arrest and p53-independent induction of apoptosis in vitro by the new anticancer drugs 5-FdUrd-P-FdCydOct and dCydPam-P-FdUrd in DU-145 human prostate cancer cells. J. Cancer Res. Clin. Oncol., 2000, 126, 247-256
52. Gmeiner, W.H.; Skradis, A.; Pon, R.T.; Liu, J. Cytotoxicity and invivo tolerance of FdUMP[10]: a novel pro-drug of the TS inhibitory nucleotide FdUMP. Nucleosides Nucleotides, 1999, 18, 1729-1730
53. Liu, J.; Skradis, A.; Kolar, C.; Kolath, J.; Anderson, J.; Lawson, T.; Talmadge, J.; Gmeiner, W.H. Increased cytotoxicity and decreased in vivo toxicity of FdUMP[10] relative to 5-FU. Nucleosides Nucleotides, 1999, 18, 1789-1802
54. Liu, J.; Kolar, C.; Lawson, T.A.; Gmeiner, W.H. Targeted drug delivery to chemoresistant cells: folic acid derivatization of FdUMP[10] enhances cytotoxicity toward 5-FU-resistant human colorectal tumor cells. J. Org. Chem., 2001, 66, 5655-5663
55. Bijnsdorp, I.V.; Comijn, E.M.; Padron, J.M.; Gmeiner, W.H.; Peters, G.J. Mechanisms of action of FdUMP[10]: metabolite activation and thymidylate synthase inhibition. Oncol. Rep., 2007, 18, 287-291
56. Liao, Z.Y.; Sordet, O.; Zhang, H.L.; Kohlhagen, G.; Antony, S.; Gmeiner, W.H.; Pommier, Y. A novel polypyrimidine antitumor agent FdUMP[10] induces thymineless death with topoisomerase I-DNA complexes. Cancer Res., 2005, 65, 4844-4851 (Pubitemid 40740823)
57. Cho, K.; Wang, X.; Nie, S.; Chen, Z.G.; Shin, D.M. Therapeutic nanoparticles for drug delivery in cancer. Clin. Cancer Res., 2008, 14, 1310-1316
58. Lammers, T.; Hennink, W.E.; Storm, G. Tumour-targeted nanomedicines: principles and practice. Br. J. Cancer, 2008, 99, 392-397
59. Patra, C.R.; Bhattacharya, R.; Wang, E.; Katarya, A.; Lau, J.S.; Dutta, S.; Muders, M.; Wang, S.; Buhrow, S.A.; Safgren, S.L.; Yaszemski, M.J.; Reid, J.M.; Ames, M.M.; Mukherjee, P.; Mukhopadhyay, D. Targeted delivery of gemcitabine to pancreatic adenocarcinoma using cetuximab as a targeting agent. Cancer Res., 2008, 68, 1970-1978
60. Couvreur, P.; Reddy, L.H.; Mangenot, S.; Poupaert, J.H.; Desmaele, D.; Lepetre-Mouelhi, S.; Pili, B.; Bourgaux, C.; Amenitsch, H.; Ollivon, M. Discovery of new hexagonal supramolecular nanostructures formed by squalenoylation of an anticancer nucleoside analogue. Small, 2008, 4, 247-253 (Pubitemid 351271158)
61. Couvreur, P.; Stella, B.; Reddy, L.H.; Hillaireau, H.; Dubernet, C.; Desmaele, D.; Lepetre-Mouelhi, S.; Rocco, F.; reuddre-Bosquet, N.; Clayette, P.; Rosilio, V.; Marsaud, V.; Renoir, J.M.; Cattel, L. Squalenoyl nanomedicines as potential therapeutics. Nano. Lett., 2006, 6, 2544-2548
62. Reddy, L.H.; Dubernet, C.; Mouelhi, S.L.; Marque, P.E.; Desmaele, D.; Couvreur, P. A new nanomedicine of gemcitabine displays enhanced anticancer activity in sensitive and resistant leukemia types. J. Control Release, 2007, 124, 20-27 (Pubitemid 350103730)
63. Reddy, L.H.; Couvreur, P. Novel approaches to deliver gemcitabine to cancers. Curr. Pharm. Des., 2008, 14, 1124-1137 (Pubitemid 351982559)
64. Reddy, L.H.; Marque, P.E.; Dubernet, C.; Mouelhi, S.L.; Desmaele, D.; Couvreur, P. Preclinical toxicology (subacute and acute) and efficacy of a new squalenoyl gemcitabine anticancer nanomedicine. J. Pharmacol. Exp. Ther., 2008, 325, 484-490 (Pubitemid 351574820)
65. Reddy, L.H.; Khoury, H.; Paci, A.; Deroussent, A.; Ferreira, H.; Dubernet, C.; Decleves, X.; Besnard, M.; Chacun, H.; Lepetre-Mouelhi, S.; Desmaele, D.; Rousseau, B.; Laugier, C.; Cintrat, J.C.; Vassal, G.; Couvreur, P. Squalenoylation favorably modifies the in vivo pharmacokinetics and biodistribution of gemcitabine in mice. Drug Metab. Dispos., 2008, 36, 1570-1577
66. Reddy, L.H.; Ferreira, H.; Dubernet, C.; Mouelhi, S.L.; Desmaele, D.; Rousseau, B.; Couvreur, P. Squalenoyl nanomedicine of gemcitabine is more potent after oral administration in leukemia-bearing rats: study of mechanisms. Anticancer Drugs, 2008, 19, 999-1006.
67. Stella, B.; Arpicco, S.; Rocco, F.; Marsaud, V.; Renoir, J.M.; Cattel, L.; Couvreur, P. Encapsulation of gemcitabine lipophilic derivatives into polycyanoacrylate nanospheres and nanocapsules. Int. J. Pharm., 2007, 344, 71-77 (Pubitemid 47464827)
68. Duncan, R. The dawning era of polymer therapeutics. Nat. Rev. Drug Discov., 2003, 2, 347-360
69. Duncan, R. Polymer conjugates as anticancer nanomedicines. Nat. Rev. Cancer, 2006, 6, 688-701.
70. Schiavon, O.; Pasut, G.; Moro, S.; Orsolini, P.; Guiotto, A.; Veronese, F.M. PEG-Ara-C conjugates for controlled release. Eur. J. Med. Chem., 2004, 39, 123-133
71. Pasut, G.; Canal, F.; Dalla, V.L.; Arpicco, S.; Veronese, F.M.; Schiavon, O. Antitumoral activity of PEG-gemcitabine prodrugs targeted by folic acid. J. Control Release, 2008, 127, 239-248
72. Bharali, D.J.; Khalil, M.; Gurbuz, M.; Simone, T.M.; Mousa, S.A. Nanoparticles and cancer therapy: a concise review with emphasis on dendrimers. Int. J. Nanomed., 2009, 4, 1-7.
73. Svenson, S. Dendrimers as versatile platform in drug delivery applications. Eur. J. Pharm. Biopharm., 2009, 71, 445-462
74. Bhadra, D.; Bhadra, S.; Jain, S.; Jain, N.K. A PEGylated dendritic nanoparticulate carrier of fluorouracil. Int. J. Pharm., 2003, 257, 111-124
75. Vinogradov, S.V. Polymeric nanogel formulations of nucleoside analogs. Expert Opin. Drug Deliv., 2007, 4, 5-17.
76. Vinogradov, S.V.; Zeman, A.D.; Batrakova, E.V.; Kabanov, A.V. Polyplex Nanogel formulations for drug delivery of cytotoxic nucleoside analogs. J. Control Release, 2005, 107, 143-157
77. Galmarini, C.M.; Warren, G.; Kohli, E.; Zeman, A.; Mitin, A.; Vinogradov, S.V. Polymeric nanogels containing the triphosphate form of cytotoxic nucleoside analogues show antitumor activity against breast and colorectal cancer cell lines. Mol. Cancer Ther., 2008, 7, 3373-3380
78. Ibrahim, N.K.; Desai, N.; Legha, S.; Soon-Shiong, P.; Theriault, R.L.; Rivera, E.; Esmaeli, B.; Ring, S.E.; Bedikian, A.; Hortobagyi, G.N.; Ellerhorst, J.A. Phase I and pharmacokinetic study of ABI-007, a Cremophor-free, protein-stabilized, nanoparticle formulation of paclitaxel. Clin. Cancer Res., 2002, 8, 1038-1044
79. Foote, M. Using nanotechnology to improve the characteristics of antineoplastic drugs: improved characteristics of nab-paclitaxel compared with solvent-based paclitaxel. Biotechnol. Annu. Rev., 2007, 13, 345-357 (Pubitemid 47387129)
80. Hawkins, M.J.; Soon-Shiong, P.; Desai, N. Protein nanoparticles as drug carriers in clinical medicine. Adv. Drug Deliv. Rev., 2008, 60, 876-885
81. Wosikowski, K.; Biedermann, E.; Rattel, B.; Breiter, N.; Jank, P.; Loser, R.; Jansen, G.; Peters, G.J. In vitro and in vivo antitumor activity of methotrexate conjugated to human serum albumin in human cancer cells. Clin. Cancer Res., 2003, 9, 1917-1926
82. Bolling, C.; Graefe, T.; Lubbing, C.; Jankevicius, F.; Uktveris, S.; Cesas, A.; Meyer-Moldenhauer, W.H.; Starkmann, H.; Weigel, M.; Burk, K.; Hanauske, A.R. Phase II study of MTX-HSA in combination with cisplatin as first line treatment in patients with advanced or metastatic transitional cell carcinoma. Invest. New Drugs, 2006, 24, 521-527 (Pubitemid 44273028)
83. Torchilin, V.P. Recent advances with liposomes as pharmaceutical carriers. Nat. Rev. Drug Discov., 2005, 4, 145-160
84. Drummond, D.C.; Meyer, O.; Hong, K.; Kirpotin, D.B.; Papahadjopoulos, D. Optimizing liposomes for delivery of chemotherapeutic agents to solid tumors. Pharmacol. Rev., 1999, 51, 691-743.
85. Lasic, D.D. Mixed micelles in drug delivery. Nature, 1992, 355, 279-280
86. Barenholz, Y. Relevancy of drug loading to liposomal formulation therapeutic efficacy. J. Liposome Res., 2003, 13, 1-8. (Pubitemid 36378121)
87. Allen, T.M.; Hansen, C.; Martin, F.; Redemann, C.; Yau-Young, A. Liposomes containing synthetic lipid derivatives of poly(ethylene glycol) show prolonged circulation half-lives in vivo. Biochim. Biophys. Acta, 1991, 1066, 29-36.
88. Allen, T.M.; Martin, F.J. Advantages of liposomal delivery systems for anthracyclines. Semin. Oncol., 2004, 31, 5-15.
89. Jehn, C.F.; Boulikas, T.; Kourvetaris, A.; Possinger, K.; Luftner, D. Pharmacokinetics of liposomal cisplatin (lipoplatin) in combination with 5-FU in patients with advanced head and neck cancer: first results of a phase III study. Anticancer Res., 2007, 27, 471-475 (Pubitemid 46363368)
90. Meerum Terwogt, J.M.; Groenewegen, G.; Pluim, D.; Maliepaard, M.; Tibben, M.M.; Huisman, A.; ten Bokkel Huinink, W.W.; Schot, M.; Welbank, H.; Voest, E.E.; Beijnen, J.H.; Schellens, J.M. Phase I and pharmacokinetic study of SPI-77, a liposomal encapsulated dosage form of cisplatin. Cancer Chemother. Pharmacol., 2002, 49, 201-210
91. Wittgen, B.P.; Kunst, P.W.; van der Born K.; van Wijk, A.W.; Perkins, W.; Pilkiewicz, F.G.; Perez-Soler, R.; Nicholson, S.; Peters, G.J.; Postmus, P.E. Phase I study of aerosolized SLIT cisplatin in the treatment of patients with carcinoma of the lung. Clin. Cancer Res., 2007, 13, 2414-2421 (Pubitemid 46698592)
92. Howell, S.B. Clinical applications of a novel sustained-release injectable drug delivery system: DepoFoam technology. Cancer J., 2001, 7, 219-227 (Pubitemid 33759108)
93. Angst, M.S.; Drover, D.R. Pharmacology of drugs formulated with DepoFoam: a sustained release drug delivery system for parenteral administration using multivesicular liposome technology. Clin. Pharmacokinet., 2006, 45, 1153-1176
94. Phuphanich, S.; Maria, B.; Braeckman, R.; Chamberlain, M. A pharmacokinetic study of intra-CSF administered encapsulated cytarabine (DepoCyt) for the treatment of neoplastic meningitis in patients with leukemia, lymphoma, or solid tumors as part of a phase III study. J. Neuroncol., 2007, 81, 201-208 (Pubitemid 44963980)
95. Chamberlain, M.C.; Kormanik, P.; Howell, S.B.; Kim, S. Pharmacokinetics of intralumbar DTC-101 for the treatment of leptomeningeal metastases. Arch. Neurol., 1995, 52, 912-917
96. Bomgaars, L.; Geyer, J.R.; Franklin, J.; Dahl, G.; Park, J.; Winick, N.J.; Klenke, R.; Berg, S.L.; Blaney, S.M. Phase I trial of intrathecal liposomal cytarabine in children with neoplastic meningitis. J. Clin. Oncol., 2004, 22, 3916-3921
97. Kim, S.; Chatelut, E.; Kim, J.C.; Howell, S.B.; Cates, C.; Kormanik, P.A.; Chamberlain, M.C. Extended CSF cytarabine exposure following intrathecal administration of DTC 101. J. Clin. Oncol., 1993, 11, 2186-2193
98. Glas, M.; Stuplich, M.; Tschampa, H.; Urbach, H.; Rasch, K.; Herrlinger, U. Liposomal cytarabine given concomitantly with radiotherapy in a patient with leptomeningeal metastasis from breast cancer. J. Neurol., 2008, 255, 1838-1839.
99. Celano, M.; Calvagno, M.G.; Bulotta, S.; Paolino, D.; Arturi, F.; Rotiroti, D.; Filetti, S.; Fresta, M.; Russo, D. Cytotoxic effects of gemcitabine-loaded liposomes in human anaplastic thyroid carcinoma cells. BMC Cancer, 2004, 4, 63. (Pubitemid 40180291)
100. Bornmann, C.; Graeser, R.; Esser, N.; Ziroli, V.; Jantscheff, P.; Keck, T.; Unger, C.; Hopt, U.T.; Adam, U.; Schaechtele, C.; Massing, U.; von, D.E. A new liposomal formulation of Gemcitabine is active in an orthotopic mouse model of pancreatic cancer accessible to bioluminescence imaging. Cancer Chemother. Pharmacol., 2008, 61, 395-405.
101. Paolino, D.; Cosco, D.; Licciardi, M.; Giammona, G.; Fresta, M.; Cavallaro, G. Polyaspartylhydrazide copolymer-based supramolecular vesicular aggregates as delivery devices for anticancer drugs. Biomacromolecules, 2008, 9, 1117-1130 (Pubitemid 351639563)
102. Celia, C.; Malara, N.; Terracciano, R.; Cosco, D.; Paolino, D.; Fresta, M.; Savino, R. Liposomal delivery improves the growth-inhibitory and apoptotic activity of low doses of gemcitabine in multiple myeloma cancer cells. Nanomedicine, 2008, 4, 155-166