Drug delivery anticancer

Brown SD, Nativo P, Smith JA, Stirling D, Edwards PR, Venugopal B, Flint DJ, Plumb JA, Graham D, Wheate NJ (2010) Gold nanoparticles for the improved anticancer drug delivery of the active component of oxaliplatin. J Am Chem Soc 132 4678-4684... 

Dufes, C., J. M. Muller, W. Couet, J. C. Olivier, I. F. Uchegbu, and A. G. Schatzlein. 2004. Anticancer drug delivery with transferrin targeted polymeric chitosan vesicles. Pharm Res 21(l) 101-7. 

HPMA copolymers are water-soluble biocompatible polymers, widely used in anticancer drug delivery (reviewed in Reference [22]). HPMA copolymers containing reactive groups at side-chain termini were previously used for the modification of trypsin [23], chymotrypsin [23,24], and acetylcholinesterase [25]. The modification dramatically increased the acetylcholinesterase survival in the blood stream of mice and the thermostability of modified enzymes when compared to the native proteins. However, the modification involved multipoint attachment of the copolymers to the substrates, which may cause crosslinking. To modify proteins or biomedical surfaces by one point attachment, semitelechelic polymers should be used. 

Sun A, Shoji M, Lu YJ, Liotta DC, Snyder JP. 2006. Synthesis of EF24-tripeptide chloromethyl ketone A novel curcumin-related anticancer drug delivery system. J Med Chem 49 3153-3158. 

Patterns of Anticancer Drug Delivery by Simulations of a Cell Cycle Automaton. Chapter 10 in this book. 

Optimizing Temporal Patterns of Anticancer Drug Delivery... 

The cases of peak delivery at 10 a.m. (Fig. 10.5b) or 10 p.m. (Fig. 10.5d) are intermediate between the two preceding cases. Overlap between the peak of 5-FU and the peak of cells in S phase is only partial, but it is still greater in the case of the peak at 10 a.m., so that this pattern is the second most toxic, followed by the circadian delivery centered around 10 p.m. The comparison of the four panels Fig. 10.5a-d explains the results of Fig. 10.4a on the marked differences in cytotoxic effects of the four 5-FU circadian delivery schedules. The use of the cell cycle automaton helps clarify the dynamic bases that underlie the distinctive effects of the peak time in the circadian pattern of anticancer drug delivery. 

Numerical simulations therefore indicate that the least damage to the cells occurs when the peak of 5-FU circadian delivery is at 4 a.m., and when cells are well synchronized, i.e., when cell cycle variability V is lowest. In contrast, when the peak of 5-FU circadian delivery is at 4 p.m., cytotoxicity is enhanced when cells are well synchronized. The cytotoxic effect of the drug, therefore, can be enhanced or diminished by increased cell cycle synchronization, depending on the relative phases of the circadian schedule of drug delivery and the cell cycle entrained by the circadian clock. Continuous infusion of 5-FU is nearly as toxic as the most cytotoxic circadian pattern of anticancer drug delivery. 

The results presented here point to the interest of measuring, both in normal and tumor cell populations, parameters such as the duration of the cell cycle phases and their variability, as well as the presence or absence of entrainment by the circadian clock. As shown by the results obtained with the cell cycle automaton model, these data are crucial for using the model to predict the differential outcome of various anticancer drug delivery schedules on normal and tumor cell populations. In a sub-... 

Altinok, A., Levi, F., Goldbeter, A. A cell cycle automaton model for probing circadian patterns of anticancer drug delivery. Adv. Drug Deliv. Rev. 2007,... 

Applications of Liposomes in Therapeutics 5.3.4.1 Anticancer Drug Delivery References... 

Ikehara Y, Kojima N (2007) Development of a novel oligomarmose-coated liposome-based anticancer drug-delivery system for intraperitoneal cancer. Curr Opin Mol Ther 9 53-61... 

Dharap, S.S., Wang, Y., Chandna, P., Khandare, J.J., Qiu, B., Gunaseelan, S., Sinko, P.J., Stein, S., Farmanfarmaian, A. and Minko, T. (2005) Tumor-specific targeting of an anticancer drug delivery system by LHRH peptide. Proc. Natl. Acad. Sci. USA, 102, 12962-12967. 

The second discovery that enabled liposomes to be developed into efficacious anticancer drug delivery systems was the development of an efficient loading procedure that resulted in liposomes with high drug concentrations. This in turn permitted a reduction in the amount of phospholipid to be administered concomitantly with a given drug dose. This advanced technique was developed during formulation studies on doxorubicin that eventually led to a liposomal formulation that is now licensed as Caelyx for the treatment of Kaposi s sarcoma and ovarian cancer. 

Figure 24 (a) A proposed new carrier for switching the release of an anticancer drug by early endosomal pH from polymeric micelles and (b) the polymeric micelles for effective anticancer drug delivery to MDR cells with receptor-mediated endocytosis, switching release rate, and fusogenic activity of polymeric micelle components. 

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