Doxorubicin biodistribution

Veronese FM, Schiavon O, Pasut G, Mendichi R, Andersson L, Tsirk A, Ford J, Wu G, Kneller S, Davies J, Duncan R (2005) PEG-doxorubicin conjugates influence of polymer structure on drug release, in vitro cytotoxicity, biodistribution, and antitumor activity. Bioconjug Chem 16 775-784... 

Bibby DC, Talmadge JE, Dalai MK, Kurz SG, Chytil KM, Barry SE, Shand DG, Steiert M (2005) Pharmacokinetics and biodistribution of RGD-targeted doxorubicin-loaded nanoparticles in tumor-bearing mice. International Journal of Pharmaceutics 293 281-290. 

Charrois GJ, Allen TM. Drug release rate influences the pharmacokinetics, biodistribution, therapeutic activity, and toxicity of pegylated liposomal doxorubicin formulations in murine breast cancer. Biochim Biophys Acta 2004 1663(1-2) 167. 

Chemotherapy refers to drug administration with highly serious side effects, such as nausea, hand and foot rashes, mouth sores, and increased risk of infection, easy bruising, and so on. Therefore, liposomal carriers have been used in order to improve the drug s biodistribution and protect the patient from those side effects. The main anticancer drugs used to treat ovarian cancer are carboplatin and cisplatin, paclitaxel, topotecan, and lurtotecan. PEGylated liposomal doxorubicin has been approved as a regimen for patients with metastatic ovarian cancer refractory to both paclitaxel and platinum based-therapy [449],... 

Siegal, T., Horowitz, A., and Gabizon, A. (1995), Doxorubicin encapsulated in sterically stabilized liposomes for the treatment of a brain tumor model Biodistribution and therapeutic efficacy,/. Neurosurg., 83,1029-1037. 

Arnold, R. D., Mager, D. E., Slack, J. E., and Straubinger, R. M. (2005), Effect of repetitive administration of Doxorubicin-containing liposomes on plasma pharmacokinetics and drug biodistribution in a rat brain tumor model, Clin. Cancer Res., 11, 8856-8865. 

However, the administration of free doxorubicin often leads to dose-limiting side effects such as cardiotoxicity and myelosu-pression. This toxicity can be reduced by liposomal encapsulation of doxorubicin because of the modified biodistribution of the drug (1). Additionally, the efficiency of the drug is improved due to the passive targeting effect of liposomes. 

However, Caelyx has still some side effects like stomatitis, hand-foot syndrome, mild myelosuppression and vomiting, which is due to uncontrolled biodistribution of Caelyx to healthy organs (3,4). Hence, there is a continued need of targeted delivery systems for doxorubicin and other drugs. 

Seo, S.B. Park, C.R. Jeong, S.Y. Biodistribution and anti-tumor efficacy of doxorubicin loaded glycol-chitosan nanoaggregates by EPR effect. J. Control. Release 2003, 91, 135-145. 

Hyung Park J, Kwon S, Lee M (2006). Self-assembled nanoparticles based on glycol chitosan bearing hydrophobic moieties as carriers for doxorubicin In vivo biodistribution and anti-tumor activity. Biomaterials. 27 119-126. 

Pimm M, Perkins AC, Strohalm J, Ulbrich K, Duncan R. Gamma scintigraphy of the biodistribution of I-labelled N-(2-hydroxypropyl)methacrylamide copolymer-doxorubicin conjugates in mice with transplanted melanoma and mammary carcinoma. J Drug Target 1996 3 375-383. 

Shiah J-G, Dvorak M, Kopeckova P, Sun Y, Peterson CM, Kopecek J. Biodistribution and antitumour efficacy of long-circulating N-(2-hydroxypropyl)methacryl unide copolymer-doxorubicin conjugates in nude mice. Eur J Cancer 2001 37 131-139. 

Ambruosi A, Khalansky AS, Yamamoto H et al (2(X)6) Biodistribution of polysorbate 80-coated doxorubicin-loaded [14C]-poly(butyl cyanoacrylate) nanoparticles after intravenous administration to gUoblastoma-bearing rats. J Drug Target 14 97-105... 

Soininen SK, Lehtolainen-DaUdlic P, Karppinen T, Puustinen T, Dragneva G, Kaikkonen MU, et al. Targeted delivery via avidin fusion protein intracellular fate of biotinylated doxorubicin derivative and cellular uptake kinetics and biodistribution of biotinylated liposomes. EurJ Pharm Sci 2012 47 848-56. 

Shiah, J. G., Dvorak, M., Kopeckova, P., et al. (2001) Biodistribution and Antitumour Efficacy of Long-Circulating N- (2-Hydroxypropyl)Methacrylamide Copolymer-Doxorubicin Conjugates in Nude Mice, Eur. J. Cancer, 37, 131-9. 

HPMA copolymer-doxorubicin has been widely evaluated in preclinical and clinical studies. It demonstrates marked advantages over free doxombidn control of biodistribution and accumulation via molecular weight restrictions [10,16,35,37,45], biodegradability [16-19,24,25,39,42], minimal immunogenicity [17-19, 25,38-44], subcellular localization [15-20], anticancer activity [33-36,43-46,54,55,57], enhanced permeability and retention [9,14,57,58], increased apoptosis [36], lipid peroxidation [57], DNA damage [57], and reduced nonspecific toxicity [14,33-35,43-46]. Recent cKnical trials in the UK provide proof of principle of the enhanced permeability and retention effect for solid tumors and the unique advantages of this novel drug delivery system for the treatment of ovarian cancer. [35,43-46]... 

Pimm, M. V., Perkins, A. C., Strohalm, J., Ulbrich, K., Duncan, R., 1996, Ganuna Scintigraphy of the Biodistribution of I-Labelied N-(2-Hydroxypropyl) Methacryllamide Copolymer-Doxorubicin Conjugates in Mice with Transplanted Melanoma and Mammary Carcinoma J. Drug Targeting 3 375-383. 

Raoul JL, Heresbach D, Bretagne JF, Ferrer DB, Duvauferrier R, Bourguet P, Messner M, Gosselin M (1992) Chemoembolization of hepatocellular carcinomas. A study of the biodistribution and pharmacokinetics of doxorubicin. Cancer 70 585-590... 

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