5FU

The clinical trial that resulted in FDA approval of bevacizumab (February 2004) was a randomized, double-blind, phase III study in which bevacizumab was administered in combination with bolus-IFL (irinotecan, 5FU, leucovorin) chemotherapy as first-line therapy for previously untreated metastatic colorectal cancer [3]. Median survival was increased from 15.6 months in the bolus-IFL + placebo arm to 20.3 months in the bolus-IFL + bevacizumab arm. 

So, in order to provide a macromolecular prodrug of 5FU with reduced side-effects, having affinity for tumor cells and exhibiting a high antitumor activity, the present paper is concerned with the design of hybrid type conjugates of chitin-... 

FU(1), chitosan-5FU(2), a-l,4-polygalactosamine-5FU(3), partially N-acetylated a-l,4-polygalactosamine-5FU(4), hyaluronic acid-5FU(5), dextran-5FU(6), and 6-0-carboxymethyl chitin(CM-chitin)-5FU(7). 

Scheme I. Preparation route for chitosan-5FU, COS6-5FU and COS3-5FU conjugates.

Scheme II. Preparation routes for a-l,4-polygalactosamine-5FU, GOS5-5FU, GOS3-5FU conjugates and partially N-acetylated-a-1,4-polygalactosamine-5FU conjugates.

Scheme III. Preparation routes for hyaluronic acid-5FU and dextran-5FU conjugates.

Moreover, chitin-5FU, chitosan-5FU, COS-5FU, a-1,4- polygalactosamine-5FU, partially N-acetylated a-1,4- polygalactosamine-5FU, GOS-5FU, hyaluronic... 

Figure 1. Survival effects for chitin-5FU conjugates(l) against p388 leukemia in mice ip/ip. D5FU=8.3mol%, D5FU=llmol%, (°) 5FU.

Figure 5. Survival effects for CM-chitin-5FU conjugate(7) and the hydrochloride salt of 4-[(amino-n-pentyl)ester]methylene-5FU(14) against p3 8 leukemia in mice ip/ip. 7(DCM Omol fc D5FU=35mol%),...

I4, (o) 5FU. aDegree of substitution of carboxymethyl groups based on the number of sugar groups. 

The results obtained suggest that such polysaccharide-5FU conjugates can be utilized as tumor therapeutical agents. 

Fluorouracil (5FU) is 5-fluoropyridrimidine-2,4(1/7, 3H)-dione. Its structure is illustrated in Figure 11. The hydrogen in the naturally occurring pyrimidine, uracil, is substituted by fluorine in the 5 position. The presence of the heteroatoms in the structure imparts hydrophilicity to the compound as they are capable of hydrogen bonding. 

Nanospheres of PLGA were prepared by emulsion-evaporation by employing homogenization and a solvent system consisting of acetone in which both the drug and polymer were dissolved [95], The encapsulation of 5FU in these nanospheres was low compared to the more hydrophobic drug, indomethacin. It was reported that the hydrophilic 5FU leaked to the aqueous phase. PGL nanoparticles were prepared by aldol condensation loading 5FU with an efficiency of 14.32% [50]. 

Alterations to the concentration of 5FU, surfactant concentration, pH, and monomer concentration were also made to effect an increase in the loading. However, in each... 

First generation of topi inhibitors were developed as drugs from camptothecins, a family of compounds derived from wood and bark of the Chinese tree Camptotheca acuminata) [9, 10], Many of these are already in clinical use or clinical trials, including irinotecan, topotecan, exatecan, rubitecan, and lurtotecan. Irinotecan (CPT-11) is bioactivated in liver by carboxylesterase to the active metabolite SN-38, 1000-fold more active [11]. Irinotecan received in 1998 FDA approval for treatment of metastatic colorectal cancer after failure of treatment with 5FU [12],... 

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