- Drug delivery to tumours using a novel 5-FU derivative encapsulated into lipid nanocapsules
-
In this work, a novel lipophilic 5-fluorouracil (5-FU) derivative was synthesised and encapsulated into lipid nanocapsules (LNC). 5-FU was modified with lauric acid to give a lipophilic mono-lauroyl-derivative (5-FU-C12, MW of about 342 g/mol, yield of reaction 70%). 5-FU-C12 obtained was efficiently encapsulated into LNC (encapsulation efficiency above 90%) without altering the physico-chemical characteristics of LNC. The encapsulation of 5-FU-C12 led to an increased stability of the drug when in contact with plasma being the drug detectable until 3 h following incubation. Cytotoxicity assay carried out using MTS on 2D cell culture showed that 5-FU-C12-loaded LNC had an enhanced cytotoxic effect on glioma (9L) and human colorectal (HTC-116) cancer cell line in comparison with 5-FU or 5-FU-C12. Then, HCT-116 tumour spheroids were cultivated and the reduction of spheroid volume was measured following treatment with drug-loaded LNC and drugs alone. Similar reduction on spheroids volume was observed following the treatment with drug-loaded LNC, 5-FU-C12 and 5-FU alone, while blank LNC displayed a reduction in cell viability only at high concentration. Globally, our data suggest that the encapsulation increased the activity of the 5-FU-C12. However, in-depth evaluations of LNC permeability into spheroids are needed to disclose the potential of these nanosystems for cancer treatment.
- Lollo, Giovanna,Matha, Kevin,Bocchiardo, Martina,Bejaud, Jér?me,Marigo, Ilaria,Virgone-Carlotta, Angelique,Dehoux, Thomas,Rivière, Charlotte,Rieu, Jean-Paul,Brian?on, Stephanie,Perrier, Thomas,Meyer, Olivier,Benoit, Jean-Pierre
-
-
Read Online
- Synthesis and bioevaluation of 5-fluorouracil derivatives
-
A series of six novel 5-fluorouracil derivatives 1-6 were synthesized and their structures confirmed by 1H- and 13C-NMR, MS and elemental analysis. The preliminary in vitro antitumor activities against B16, K562 and CHO cells and the in vivo inhibitions of liver cancer H22 demonstrated that some of these compounds effectively inhibit the growth of tumor cells, but the in vivo trials in mice revealed that the compounds also exhibited serious liver and lung tissue toxicity. The hydrolysis experiments indicated that this type of compound did not readily liberate 5-fluorouracil, as expected.
- Tian, Zhi-Yong,Du, Gang-Jun,Xie, Song-Qiang,Zhao, Jin,Gao, Wen-Yuan,Wang, Chao-Jie
-
-
Read Online
- DRUG FORMULATIONS FOR CANCER TREATMENT
-
Compounds and pharmaceutical formulations containing these compounds are described. Also described are methods of making and using the compounds. The compounds include nucleobases, nucleobase analogues, or combinations thereof. In one embodiment, a nucleobase analogue is combined with doxorubicin and encapsulated within a liposome for use in inhibiting or preventing the growth of cancer cells. Further described are pharmaceutical compositions containing two or more therapeutically active agents encapsulated within a vesicle, such as a liposome, wherein the molar ratio of the agents provides a synergistic therapeutic effect.
- -
-
Page/Page column 46; 47
(2017/07/27)
-
- Synthesis of allyloxycarbonyloxymethyl-5-fluorouracil and copolymerizations with N-vinylpyrrolidinone
-
Poly(N-vinylpyrrolidinone) (PNVP) bearing 5-fluorouracil (5-FU) moieties was synthesised via a three-step method. Firstly, 5-FU reacted with formaldehyde to form a mixture of mono- and disubstituted hydroxymethyl-5-FUs. The mixture was then treated with allyl chloroformate to afford allyloxycarbonyloxymethyl-5-FUs. This reaction showed site-specificity: the hydroxymethyl goup at the N-I position readily reacted with chloroformate whereas the N-3 hydroxymethyl group partially decomposed into formaldehyde and the amide group. 1-Allyloxycarbonyloxymethyl-5-FU (4) and NVP were copolymerized in dioxane using azobisisobutyronitrile as an initiator. The monomer reactivity ratios, r4= 0.32 and r(NVP)= 0.97, were evaluated by both linear and non-linear methods.
- Liu,Fullwood,Rimmer
-
p. 1771 - 1775
(2007/10/03)
-