Formulation and Pharmacokinetics of Thermosensitive Stealth(®) Liposomes Encapsulating 5-Fluorouracil. Al Sabbagh, C., Tsapis, N., Novell, A., Calleja-Gonzalez, P., Escoffre, J.M, Bouakaz, A., Chacun, H., Denis, S., Vergnaud, J., Gueutin, C., & Fattal, E. Pharmaceutical research, November, 2014. Paper doi abstract bibtex PURPOSE: We optimize the encapsulation and investigate the pharmacokinetics of 5-Fluorouracil (5-FU) delivered by thermosensitive stealth(®) liposomes (TSLs) designed to trigger drug release upon hyperthermia using focused ultrasound (FUS). METHODS: 5-FU was encapsulated into liposomes made of 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine/cholesterol/1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-PEG2000 either as a free molecule or complexed with copper-polyethylenimine. Heat-triggered drug release was evaluated using either a water bath or FUS. Formulation cytotoxicity was assessed on HT-29 cell line by MTS assay. Pharmacokinetics and biodistribution of 5-FU were evaluated in HT-29-tumor bearing mice. RESULTS: 5-FU was easily encapsulated using the lipid hydration method (encapsulation efficacy of 13%) but poorly retained upon dilution. 5-FU complexation with copper-polyethylenimine improved 5-FU retention into liposomes and allowed to obtain an encapsulation efficacy of 37%. At 42°C, heat-triggered 5-FU release from TSLs was 63% using a water bath and 68% using FUS, within 10 min, whereas it remained below 20% for the non-thermosensitive formulation. The MTS assay revealed that formulation toxicity arose from 5-FU and not from the excipients. In addition, 5-FU complex encapsulation into TSLs induces a reduction of the IC50 from 115 down to 49 $μ$M. Pharmacokinetics reveals a longer circulation of encapsulated 5-FU and a more important body exposure, although tumor passive targeting is not significantly higher than free 5-FU. CONCLUSIONS: Complexation of 5-FU with copper-polyethylenimine appears an interesting strategy to improve 5-FU retention into TSLs in vitro and in vivo. TSLs allow heat-triggered release of the drug within 10 min at 42°C, a reasonable time for future in vivo experiments.
@article{ AlSabbagh2014,
abstract = {PURPOSE: We optimize the encapsulation and investigate the pharmacokinetics of 5-Fluorouracil (5-FU) delivered by thermosensitive stealth(®) liposomes (TSLs) designed to trigger drug release upon hyperthermia using focused ultrasound (FUS).
METHODS: 5-FU was encapsulated into liposomes made of 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine/cholesterol/1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-PEG2000 either as a free molecule or complexed with copper-polyethylenimine. Heat-triggered drug release was evaluated using either a water bath or FUS. Formulation cytotoxicity was assessed on HT-29 cell line by MTS assay. Pharmacokinetics and biodistribution of 5-FU were evaluated in HT-29-tumor bearing mice.
RESULTS: 5-FU was easily encapsulated using the lipid hydration method (encapsulation efficacy of 13%) but poorly retained upon dilution. 5-FU complexation with copper-polyethylenimine improved 5-FU retention into liposomes and allowed to obtain an encapsulation efficacy of 37%. At 42°C, heat-triggered 5-FU release from TSLs was 63% using a water bath and 68% using FUS, within 10 min, whereas it remained below 20% for the non-thermosensitive formulation. The MTS assay revealed that formulation toxicity arose from 5-FU and not from the excipients. In addition, 5-FU complex encapsulation into TSLs induces a reduction of the IC50 from 115 down to 49 $μ$M. Pharmacokinetics reveals a longer circulation of encapsulated 5-FU and a more important body exposure, although tumor passive targeting is not significantly higher than free 5-FU.
CONCLUSIONS: Complexation of 5-FU with copper-polyethylenimine appears an interesting strategy to improve 5-FU retention into TSLs in vitro and in vivo. TSLs allow heat-triggered release of the drug within 10 min at 42°C, a reasonable time for future in vivo experiments.},
author = {{Al Sabbagh}, Chantal and Tsapis, Nicolas and Novell, Anthony and Calleja-Gonzalez, Patricia and Escoffre, Jean-Michel and Bouakaz, Ayache and Chacun, Hélène and Denis, Stéphanie and Vergnaud, Juliette and Gueutin, Claire and Fattal, Elias},
doi = {10.1007/s11095-014-1559-0},
issn = {1573-904X},
journal = {Pharmaceutical research},
month = {November},
pmid = {25416027},
title = {{Formulation and Pharmacokinetics of Thermosensitive Stealth(®) Liposomes Encapsulating 5-Fluorouracil.}},
url = {http://www.ncbi.nlm.nih.gov/pubmed/25416027},
year = {2014}
}
Downloads: 0
{"_id":"RhF3aY3yLWWhSroA2","authorIDs":[],"author_short":["Al Sabbagh, C.","Tsapis, N.","Novell, A.","Calleja-Gonzalez, P.","Escoffre, J.M","Bouakaz, A.","Chacun, H.","Denis, S.","Vergnaud, J.","Gueutin, C.","Fattal, E."],"bibbaseid":"alsabbagh-tsapis-novell-callejagonzalez-escoffre-bouakaz-chacun-denis-vergnaud-gueutin-fattal-formulationandpharmacokineticsofthermosensitivestealthliposomesencapsulating5fluorouracil-2014","bibdata":{"abstract":"PURPOSE: We optimize the encapsulation and investigate the pharmacokinetics of 5-Fluorouracil (5-FU) delivered by thermosensitive stealth(®) liposomes (TSLs) designed to trigger drug release upon hyperthermia using focused ultrasound (FUS). METHODS: 5-FU was encapsulated into liposomes made of 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine/cholesterol/1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-PEG2000 either as a free molecule or complexed with copper-polyethylenimine. Heat-triggered drug release was evaluated using either a water bath or FUS. Formulation cytotoxicity was assessed on HT-29 cell line by MTS assay. Pharmacokinetics and biodistribution of 5-FU were evaluated in HT-29-tumor bearing mice. RESULTS: 5-FU was easily encapsulated using the lipid hydration method (encapsulation efficacy of 13%) but poorly retained upon dilution. 5-FU complexation with copper-polyethylenimine improved 5-FU retention into liposomes and allowed to obtain an encapsulation efficacy of 37%. At 42°C, heat-triggered 5-FU release from TSLs was 63% using a water bath and 68% using FUS, within 10 min, whereas it remained below 20% for the non-thermosensitive formulation. The MTS assay revealed that formulation toxicity arose from 5-FU and not from the excipients. In addition, 5-FU complex encapsulation into TSLs induces a reduction of the IC50 from 115 down to 49 $μ$M. Pharmacokinetics reveals a longer circulation of encapsulated 5-FU and a more important body exposure, although tumor passive targeting is not significantly higher than free 5-FU. CONCLUSIONS: Complexation of 5-FU with copper-polyethylenimine appears an interesting strategy to improve 5-FU retention into TSLs in vitro and in vivo. TSLs allow heat-triggered release of the drug within 10 min at 42°C, a reasonable time for future in vivo experiments.","author":["Al Sabbagh, Chantal","Tsapis, Nicolas","Novell, Anthony","Calleja-Gonzalez, Patricia","Escoffre, Jean-Michel","Bouakaz, Ayache","Chacun, Hélène","Denis, Stéphanie","Vergnaud, Juliette","Gueutin, Claire","Fattal, Elias"],"author_short":["Al Sabbagh, C.","Tsapis, N.","Novell, A.","Calleja-Gonzalez, P.","Escoffre, J.M","Bouakaz, A.","Chacun, H.","Denis, S.","Vergnaud, J.","Gueutin, C.","Fattal, E."],"bibtex":"@article{ AlSabbagh2014,\n abstract = {PURPOSE: We optimize the encapsulation and investigate the pharmacokinetics of 5-Fluorouracil (5-FU) delivered by thermosensitive stealth(®) liposomes (TSLs) designed to trigger drug release upon hyperthermia using focused ultrasound (FUS).\n\nMETHODS: 5-FU was encapsulated into liposomes made of 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine/cholesterol/1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-PEG2000 either as a free molecule or complexed with copper-polyethylenimine. Heat-triggered drug release was evaluated using either a water bath or FUS. Formulation cytotoxicity was assessed on HT-29 cell line by MTS assay. Pharmacokinetics and biodistribution of 5-FU were evaluated in HT-29-tumor bearing mice.\n\nRESULTS: 5-FU was easily encapsulated using the lipid hydration method (encapsulation efficacy of 13%) but poorly retained upon dilution. 5-FU complexation with copper-polyethylenimine improved 5-FU retention into liposomes and allowed to obtain an encapsulation efficacy of 37%. At 42°C, heat-triggered 5-FU release from TSLs was 63% using a water bath and 68% using FUS, within 10 min, whereas it remained below 20% for the non-thermosensitive formulation. The MTS assay revealed that formulation toxicity arose from 5-FU and not from the excipients. In addition, 5-FU complex encapsulation into TSLs induces a reduction of the IC50 from 115 down to 49 $μ$M. Pharmacokinetics reveals a longer circulation of encapsulated 5-FU and a more important body exposure, although tumor passive targeting is not significantly higher than free 5-FU.\n\nCONCLUSIONS: Complexation of 5-FU with copper-polyethylenimine appears an interesting strategy to improve 5-FU retention into TSLs in vitro and in vivo. TSLs allow heat-triggered release of the drug within 10 min at 42°C, a reasonable time for future in vivo experiments.},\n author = {{Al Sabbagh}, Chantal and Tsapis, Nicolas and Novell, Anthony and Calleja-Gonzalez, Patricia and Escoffre, Jean-Michel and Bouakaz, Ayache and Chacun, Hélène and Denis, Stéphanie and Vergnaud, Juliette and Gueutin, Claire and Fattal, Elias},\n doi = {10.1007/s11095-014-1559-0},\n issn = {1573-904X},\n journal = {Pharmaceutical research},\n month = {November},\n pmid = {25416027},\n title = {{Formulation and Pharmacokinetics of Thermosensitive Stealth(®) Liposomes Encapsulating 5-Fluorouracil.}},\n url = {http://www.ncbi.nlm.nih.gov/pubmed/25416027},\n year = {2014}\n}","bibtype":"article","doi":"10.1007/s11095-014-1559-0","id":"AlSabbagh2014","issn":"1573-904X","journal":"Pharmaceutical research","key":"AlSabbagh2014","month":"November","pmid":"25416027","title":"Formulation and Pharmacokinetics of Thermosensitive Stealth(®) Liposomes Encapsulating 5-Fluorouracil.","type":"article","url":"http://www.ncbi.nlm.nih.gov/pubmed/25416027","year":"2014","bibbaseid":"alsabbagh-tsapis-novell-callejagonzalez-escoffre-bouakaz-chacun-denis-vergnaud-gueutin-fattal-formulationandpharmacokineticsofthermosensitivestealthliposomesencapsulating5fluorouracil-2014","role":"author","urls":{"Paper":"http://www.ncbi.nlm.nih.gov/pubmed/25416027"},"downloads":0},"bibtype":"article","biburl":"https://docs.google.com/uc?authuser=0&id=0B2xmYAQCJf7AaGJqTVhlWVNoMjQ&export=download","creationDate":"2014-12-04T15:14:13.160Z","downloads":0,"keywords":[],"search_terms":["formulation","pharmacokinetics","thermosensitive","stealth","liposomes","encapsulating","fluorouracil","al sabbagh","tsapis","novell","calleja-gonzalez","escoffre","bouakaz","chacun","denis","vergnaud","gueutin","fattal"],"title":"Formulation and Pharmacokinetics of Thermosensitive Stealth(®) Liposomes Encapsulating 5-Fluorouracil.","year":2014,"dataSources":["EtjZYJPqwuNhYrhrE"]}