5-Fluorouracil, poly

Fluorouracil Poly(caprolactone) Dispersions, [FUPC] Monolithic dispersions of 5-FU in poly(caprolactone) were prepared by melting the polymer on a hotplate at about 70 C and then mixing the 5-FU into this molten mass. After solidification, the sample was pulverized in a Waring Blendor prior to use. 

Ai-Zheng, C., Xi-Ming, R, Yun-Qing, K., Li, L., Ya-Dong, Y., Guang-Fu, Y. (2006). Preparation of 5-fluorouracil-poly(L-lactide) microparticles using solution-enhanced dispersion by supercritical CO2, MacromoL Rapid Commun., 27,1254-1259. 

Biodegradable poly(phosphoester-urethanes) containing bisglycophosphite as the chain extender were synthesized. Methylene bis-4-phenyl isocyanate (MDI) and toluene diisocyanate (TDI) were initially used as diisocyanates. Since there was a concern that the degradation products could be toxic, the ethyl 2,6-diisocyanatohexanoate (LDI) was synthesized and replaced the MDI (or TDI). The hydrolytic stability and solubility of these polymers were tested. Preliminary release studies of 5-fluorouracil from MDI based poly(phosphoester-urethane) and methotrexate from LDI based poly(phosphoester-urethane) are also reported. 

However, in many cases the structure of the drug does not match the structure of the reactive groups on the polymeric carrier. In this case, the structure of at least one reactant has to be modified before conjugation. Derivatives of 5-fluorouracil, namely l-(3-bromopropionyl)-5-fluorouracil, 1-chlorocarbonyl-5-fluorouracil, and l-(4-bromobutyl)-5-fluorouracil were synthesized to permit the drug attachment to poly(L-cysteine) [146] (Fig. 6). 

Fig. 6. Examples of attachment of 5-fluorouracil to cysteine residues in poly(amino acid) carriers (according to [146])...

Einmahl, S., Zignani, M., Varesio, E., Heller, J., Veuthey, J.L., Tabatabay, C., and Gumy, R. (1999). Concomitant and controlled release of dexamethasone and 5-fluorouracil from poly(ortho ester). Int. J. Pharmaceut., 185, 189-198. 

Maa, Y., and Heller, J. Controlled release of 5-fluorouracil from linear poly(ortho... 

V. Corbrion, et al., Precipitation of fluorouracil in elastomeric infusers with a poly-isoprene and in polypropylene syringes with elastomeric joint. Am. J. Health Sys. Pharmacol. 54 1845-1848, 1997. 

As in the case of electrochemical reduction, the photochemical transformation of 5-fluorouracil derivatives differs from that of the other 5-halogeno uracils. The primary photoproduct of 5-fluorouracil, its glycosides and poly(5-FU) is the photohydrate. However, at shorter wavelengths of irradiation, e.g. 254 nm where the photohydrate exhibits absorption, there is elimination of HF from the 5,6 bond and formation of barbituric acid 129 13I>. There is also some evidence for acetone photosensitized formation of cyclobutane dimers of 5-fluorouracil132), as well as dimer formation in irradiated poly(5-FU)133>. 

Garcia, O. Trigo, R.M. Blanco, M.D. Teijon, J.M. Influence of degree of crosslinking on 5-fluorouracil release from poly(2-hydroxyethyl methacrylate) hydrogels. Biomaterials 1994, 15, 689-694. 

Blanco, M.D. Garcia, O. Gomez, C. Sastre, R.L. Teij6n, J.M. In vivo drug delivery of 5-fluorouracil using poly-(2-hydroxyethyl methacrylate-co-acrylamide) hydrogels. J. Pharm. Pharmacol. 2000, 52, 1319-1325. 

Ouchi, T., H. Yuyama, and O. Yogi, Synthesis of poly(ethylene glycol)-bound 3-(5-fluorouracil-l-yl)propanoic acid, its hydrolysis reactivity and antitmnor activity. Makromol. Chem., Rapid Commun., 1985, 6, 815-819. 

Figure 9.17 Release of anticancer drugs from poly(HEMAF-collagen hydrogels. Controlled release of 5-fluorouracil 130), mitomycin C (M, 334), and bleomycin Ml 1,417) into phosphate-buffered water at 37 °C from p(HEMA) polymerized in the presence of drug and 5% eoUagen. The hydrogels were hydrated ( 40% water) throughout the experiment. Adapted from [57].

Seymour LW, Duncan R, Duffy J, Ng SY, Heller J. Poly(ortho ester) matrices for controlled-release of the antitumor agent 5-fluorouracil. J Control Release 1994 31 201 206. 

Rejinold, N. S., Chennazhi, K. P., Nair, S. V., Tamura, H., Jayakumar, R. (2011). Biodegradable and thermo-sensitive chitosan-g-poly (N-vinylcaprolactam) nanoparticles as a 5-fluorouracil carrier,... 

Grafts of poly(NIPAAm) have also been used to impart temperature responsive behavior to natural biomaterials for drug delivery, converting them into physically crosslinking hydrogels above the LCST of the poly(NIPAAm) portions. For example, poly(NIPAAm) grafted onto hyaluronic acid formed a gel upon injection which had a 12-hour burst release of riboflavin followed by sustained release (Ha et al. 2006). Similarly, chitosan with grafted poly(NIPAAm) was shown to release 5-fluorouracil at a controlled rate (J.W. Bae et al. 2006). 

Figure 6.10 Synthesis of a 5-Fluorouracil Bonded to Poly(phosphoester) (32)...

A pol mer-drug conjugate is obtained by the reaction of a chlorinated poly(phosphoester) with the 5-fluorouracil derivative in the... 

Chaturvedi, K., Kulkarni, A.R., and Aminabhavi, T.M. (2011) Blend microspheres of poly (3-hydroxybutyrate) and cellulose acetate phthalate for colon delivery of 5-fluorouracil. Ind. Eng. 

Rejinold NS, Chennazhi KP, Nair SV et al (2011) Biodegradable and thermo-responsive chitosan-g-poly(N-vinylcaprolactum) nanoparticles as a 5-fluorouracil carrier. Carbohydr Polym 83 776-786... 

Wang G, Tucker IG, Roberts MS et al (1996) In vitro and in vivo evaluation in rabbits of a controlled release 5-fluorouracil subconjunctival implant based on poly (d, L-lactide-co-glycolide). Pharm Res 13 1059-1064... 

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