Pharmacologic Studies of a Prodrug of Mitomycin C in Pegylated Liposomes (Promitil®): High Stability in Plasma and Rapid Thiolytic Prodrug Activation in Tissues

Pharmaceutical Research

Volumn 33, Issue 3, 2016, Pages 686-700

  Amitay, Yasmine ^a   Shmeeda, Hilary ^b   Patil, Yogita ^c   Gorin, Jenny ^a,b   Tzemach, Dina ^b   Mak, Lidia ^b   Ohana, Patricia ^a   Gabizon, Alberto ^b,c  

^a Lipomedix Pharmaceuticals Ltd   (Israel)

^b SHAARE ZEDEK MEDICAL CENTER   (Israel)

^c HEBREW UNIVERSITY OF JERUSALEM   (Israel)

Author keywords

cancer chemotherapy; dithiothreitol; drug delivery systems; liposome; mitomycin C; pharmacokinetics; prodrug

Indexed keywords

CHOLESTEROL; DITHIOTHREITOL; LIPID; LIPOSOME; MITOMYCIN; PEGYLATED LIPOSOMAL MITOMYCIN C LIPID BASED PRODRUG; PRODRUG; PROMITIL; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG EXCRETION; DRUG HALF LIFE; EX VIVO STUDY; EXPERIMENTAL MODEL; FEMALE; IN VITRO STUDY; IN VIVO STUDY; LIVER; LUNG; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; RAT; SPLEEN; TISSUE HOMOGENATE; TUMOR MODEL; ANIMAL; BAGG ALBINO MOUSE; DRUG STABILITY; HALF LIFE TIME; MEDICINAL CHEMISTRY; METABOLISM; NUDE MOUSE; PIG; PLASMA; PROCEDURES; SPRAGUE DAWLEY RAT; TISSUE DISTRIBUTION;

ANIMALS; CHEMISTRY, PHARMACEUTICAL; CHOLESTEROL; DITHIOTHREITOL; DRUG STABILITY; FEMALE; HALF-LIFE; LIPOSOMES; LIVER; LUNG; MALE; MICE; MICE, INBRED BALB C; MICE, NUDE; MITOMYCIN; PLASMA; PRODRUGS; RATS; RATS, SPRAGUE-DAWLEY; SPLEEN; SWINE; TISSUE DISTRIBUTION;

EID: 84957916714     PISSN: 07248741     EISSN: 1573904X     Source Type: Journal    
DOI: 10.1007/s11095-015-1819-7     Document Type: Article

References (33)

1. Doll DC, Weiss RB, Issell BF. Mitomycin: ten years after approval for marketing. J Clin Oncol. 1985;3:276-86.
2. Sartorelli AC, Hodnick WF, Belcourt MF, Tomasz M, Haffty B, Fischer JJ, et al. Mitomycin C: a prototype bioreductive agent. Oncol Res. 1994;6:501-8.
3. Paz MM, Zhang X, Lu J, Holmgren A. A new mechanism of action for the anticancer drug mitomycin C: mechanism-based inhibition of thioredoxin reductase. Chem Res Toxicol. 2012;25:1502-11.
4. Tomasz M. Mitomycin C: small, fast and deadly (but very selective). Chem Biol. 1995;2:575-9.
5. Villarroel MC, Rajeshkumar NV, Garrido-Laguna I, De Jesus-Acosta A, Jones S, Maitra A, et al. Personalizing cancer treatment in the age of global genomic analyses: PALB2 gene mutations and the response to DNA damaging agents in pancreatic cancer. Mol Cancer Ther. 2011;10:3-8.
6. Valavaaraand R, Nordman E. Renal complications of mitomycin C therapy with special reference to the total dose. Cancer. 1985;55:47-50.
7. Ihnat MA, Nervi AM, Anthony SP, Kaltreider RC, Warren AJ, Pesce CA, et al. Effects of mitomycin C and carboplatin pretreatment on multidrug resistance-associated P-glycoprotein expression and on subsequent suppression of tumor growth by doxorubicin and paclitaxel in human metastatic breast cancer xenografted nude mice. Oncol Res. 1999;11:303-10.
8. Bass PD, Gubler DA, Judd TC, Williams RM. Mitomycinoid alkaloids: mechanism of action, biosynthesis, total syntheses, and synthetic approaches. Chem Rev. 2013;113:6816-63.
9. Gabizon AA, Tzemach D, Horowitz AT, Shmeeda H, Yeh J, Zalipsky S. Reduced toxicity and superior therapeutic activity of a mitomycin C lipid-based prodrug incorporated in pegylated liposomes. Clin Cancer Res. 2006;12:1913-20.
10. Zalipsky S, Saad M, Kiwan R, Ber E, Yu N, Minko T. Antitumor activity of new liposomal prodrug of mitomycin C in multidrug resistant solid tumor: insights of the mechanism of action. J Drug Target. 2007;15:518-30.
11. Nguyen P, Awwad RT, Smart DD, Spitz DR, Gius D. Thioredoxin reductase as a novel molecular target for cancer therapy. Cancer Lett. 2006;236:164-74.
12. Biaglowand JE, Miller RA. The thioredoxin reductase/thioredoxin system: novel redox targets for cancer therapy. Cancer Biol Ther. 2005;4:6-13.
13. Lincoln DT, Ali Emadi EM, Tonissen KF, Clarke FM. The thioredoxin-thioredoxin reductase system: over-expression in human cancer. Anticancer Res. 2003;23:2425-33.
14. Powisand G, Kirkpatrick DL. Thioredoxin signaling as a target for cancer therapy. Curr Opin Pharmacol. 2007;7:392-7.
15. Powis G, Mustacich D, Coon A. The role of the redox protein thioredoxin in cell growth and cancer. Free Radic Biol Med. 2000;29:312-22.
16. Gabizon A, Amitay Y, Tzemach D, Gorin J, Shmeeda H, Zalipsky S. Therapeutic efficacy of a lipid-based prodrug of mitomycin C in pegylated liposomes: studies with human gastro-entero-pancreatic ectopic tumor models. J Control Release. 2012;160:245-53.
17. Golan T, Grenader T, Ohana P, Amitay Y, Shmeeda H, La-Beck NM, et al. Pegylated liposomal mitomycin C prodrug enhances tolerance of mitomycin C: a phase 1 study in advanced solid tumor patients. Cancer Med. 2015;4:1472-83.
18. Shmeeda H, Even-Chen S, Honen R, Cohen R, Weintraub C, Barenholz Y. Enzymatic assays for quality control and pharmacokinetics of liposome formulations: comparison with nonenzymatic conventional methodologies. Methods Enzymol. 2003;367:272-92.
19. Shmeeda H, Amitay Y, Gorin J, Tzemach D, Mak L, Ogorka J, et al. Delivery of zoledronic acid encapsulated in folate-targeted liposome results in potent in vitro cytotoxic activity on tumor cells. J Control Release. 2010;146:76-83.
20. Derksen JT, Morselt HW, Scherphof GL. Uptake and processing of immunoglobulin-coated liposomes by subpopulations of rat liver macrophages. Biochim Biophys Acta. 1988;971:127-36.
21. Paz MM. Cross-linking of dithiols by mitomycin C. Chem Res Toxicol. 2010;23:1384-92.
22. Verweijand J, Pinedo HM. Mitomycin C: mechanism of action, usefulness and limitations. Anticancer Drugs. 1990;1:5-13.
23. Adler-Mooreand J, Proffitt RT. AmBisome: liposomal formulation, structure, mechanism of action and pre-clinical experience. J Antimicrob Chemother. 2002;49 Suppl 1:21-30.
24. Kratz F, Warnecke A, Scheuermann K, Stockmar C, Schwab J, Lazar P, et al. Probing the cysteine-34 position of endogenous serum albumin with thiol-binding doxorubicin derivatives. Improved efficacy of an acid-sensitive doxorubicin derivative with specific albumin-binding properties compared to that of the parent compound. J Med Chem. 2002;45:5523-33.
25. Gabizon A, Shmeeda H, Barenholz Y. Pharmacokinetics of pegylated liposomal Doxorubicin: review of animal and human studies. Clin Pharmacokinet. 2003;42:419-36.
26. Toy R, Hayden E, Shoup C, Baskaran H, Karathanasis E. The effects of particle size, density and shape on margination of nanoparticles in microcirculation. Nanotechnology. 2011;22:115101.
27. Ali Khanand H, Mutus B. Protein disulfide isomerase a multifunctional protein with multiple physiological roles. Front Chem. 2014;2:70.
28. Paz MM. Reductive activation of mitomycin C by thiols: kinetics, mechanism, and biological implications. Chem Res Toxicol. 2009;22:1663-8.
29. Lang W, Mao J, Doyle TW, Almassian B. Isolation and identification of urinary metabolites of porfiromycin in dogs and humans. Drug Metab Dispos. 2000;28:899-904.
30. Maeda H, Nakamura H, Fang J. The EPR effect for macromolecular drug delivery to solid tumors: Improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo. Adv Drug Deliv Rev. 2013;65:71-9.
31. Gabizon A, Shmeeda H, Grenader T. Pharmacological basis of pegylated liposomal doxorubicin: impact on cancer therapy. Eur J Pharm Sci. 2012;45:388-98.
32. Pennington JD, Jacobs KM, Sun L, Bar-Sela G, Mishra M, Gius D. Thioredoxin and thioredoxin reductase as redox-sensitive molecular targets for cancer therapy. Curr Pharm Des. 2007;13:3368-77.
33. Arnerand ES, Holmgren A. The thioredoxin system in cancer. Semin Cancer Biol. 2006;16:420-6.