Delivery tumoral

Tumor 25% of the total mass of the liver by CT scan = use 2 GBq whole liver delivery Tumor > 25% but < 50% of liver mass by CT scan = use 2.5 GBq whole liver delivery Tumor > 50% of liver mass by CT scan = 3 GBq for whole liver delivery... 

Liposomal encapsulation of DOX or DNR Preferred anthracycline delivery to the tumor Breast cancer, ovarian cancer, AIDS-related Kaposi s sarcoma, multiple myeloma (pegylated liposomal DOX). Breast cancer (uncoated liposomal DOX). AIDS-related Kaposi s sarcoma, acute mye-loblastic leukemia, multiple myeloma, non-Hodgkin s lymphomas (uncoated liposomal DNR)... 

DOX, as EPI seems to form fewer amounts of ROS and secondary alcohol metabolite, (ii) encapsulation of anthracyclines in uncoated or pegylated liposomes that ensure a good drug delivery to the tumor but not to the heart, (iii) conjugation of anthracyclines with chemical moieties that are selectively recognized by the tumor cells, (iv) coadministration of dexrazoxane, an iron chelator that diminishes the disturbances of iron metabolism and free radical formation in the heart, and (v) administration of anthracyclines by slow infusion rather than 5-10 min bolus (Table 1). Pharmacological interventions with antioxidants have also been considered, but the available clinical studies do not attest to an efficacy of this strategy. 

Arap W, Pasqualini R, Ruoslahti E (1998) Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. Science 279 377-380... 

Strobel et al. (101) reported a unique approach to delivery of anticancer agents from lactide/glycolide polymers. The concept is based on the combination of misonidazole or adriamycin-releasing devices with radiation therapy or hyperthermia. Prototype devices consisted of orthodontic wire or sutures dip-coated with drug and polymeric excipient. The device was designed to be inserted through a catheter directly into a brain tumor. In vitro release studies showed the expected first-order release kinetics on the monolithic devices. 

W. E., Long-acting delivery systems for polypeptides. Inhibition of rat prostate tumors by controlled release of [D-Trp ]-LHRH from injectable microcapsules, Proc. Natl. Acad. Sci. 

Intraperitoneal administration of chemotherapeutic agents has been used for many years as a way of increasing the delivery of drugs to tumors (e.g., ovarian carcinoma) located in the peritoneal cavity (Markman, 1986 Howell and Zimra, 1988). Cisplatin (Casper et al., 1983 Markman et al., 1985), cytosine arabinoside (Ara-C) (King et al., 1984 Markman et al., 1985, 1986), and bleomycin (Markman et al., 1986) are examples of intraperitoneally administered drugs which were already successfully applied in clinical settings. 

Yatvin, M. B., Miihlensiepen, H., Porschen, W., Weinstein, J. N., and Feinendegen, L. E. (1981). Selective delivery of liposome-associated cis-dichlorodiammineplatinum(II) by heat and its influence on tumor drug uptake and growth. Cancer Res.. 41. 1602-1607. 

Micellar nanocarriers have already been applied successfully for delivery of hydro-phobic drugs [86]. These carriers are usually the product of self-assembled block copolymers, consisting of a hydrophilic block and a hydrophobic block. Generally, an ELP with a transition temperature below body temperature is used as hydrophobic block and the hydrophilic block can be an ELP with a transition temperature above body temperature or another peptide or protein. The EPR effect also directs these types of carriers towards tumor tissue. 

The Chilkoti group applied the local injection approach for intratumoral dmg delivery. ELP[V-120], with a transition at 27°C, was designed and labeled with C, 1 or 1 for radiotherapy. The first two labels were used to monitor tumor retention of the ELP and the last label was addressed to equip the ELP with antitumor activity. It was found that mice treated with 1-labeled ELP[V-120] experienced a significantly prolonged survival over those treated with saline [97]. 

Upadhyay KK, Bhatt AN, Mishra AK, Dwarakanath BS, Jain S, Schatz C, Le Meins JE, Earooque A, Chandraiah G, Jain AK, Misra A, Lecommandoux S (2010) The intracellular drug delivery and anti tumor activity of doxorubicin loaded poly(y-benzyl L-glutamate)-b-hyaluronan polymersomes. Biomaterials 31(10) 2882... 

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