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Transferrin and its oligomer: Intrac...

Lim, Ching-Jou.

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Transferrin and its oligomer: Intracellular processing and applications as drug carriers.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Transferrin and its oligomer: Intracellular processing and applications as drug carriers./
作者:	Lim, Ching-Jou.
面頁冊數:	182 p.
附註:	Source: Dissertation Abstracts International, Volume: 67-05, Section: B, page: 2499.
Contained By:	Dissertation Abstracts International67-05B.
標題:	Health Sciences, Pharmacy. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3220124
ISBN:	9780542713309

Transferrin and its oligomer: Intracellular processing and applications as drug carriers.
Lim, Ching-Jou.

Transferrin and its oligomer: Intracellular processing and applications as drug carriers. - 182 p.

Source: Dissertation Abstracts International, Volume: 67-05, Section: B, page: 2499.

Thesis (Ph.D.)--University of Southern California, 2005.

To investigate if the cross-linking of transferrin receptor (TfR) induced by Tf-oligomers can alter the endocytosis of receptor-ligand complexes and hence increases intracellular drug release. Pulse chase and cellular uptake studies have demonstrated that the intracellular retention and degradation of Tf-oligomers were significantly higher than that of monomeric Tf in cultured tumor cells. To further demonstrate that this alteration of TfR-trafficking can facilitate the intracellular release of the drug from the Tf-conjugated form, methotrexate (MTX) was conjugated to Tf-oligomer (Agg-Tf-MTX) or monomeric-Tf (Mono-Tf-MTX). Agg-Tf-MTX was 2- to 3-fold more potent than that of Mono-Tf-MTX in tumor cell lines. In addition, Agg-Tf-MTX was more potent than Mono-Tf-MTX in overcoming the drug resistance. Therefore, Tf-oligomers are potentially effective TfR-targeting carriers for intracellular delivery of anti-cancer drugs.

ISBN: 9780542713309Subjects--Topical Terms:

1017737
Health Sciences, Pharmacy.

Transferrin and its oligomer: Intracellular processing and applications as drug carriers.
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245 1 0 $a Transferrin and its oligomer: Intracellular processing and applications as drug carriers.
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500 $a Source: Dissertation Abstracts International, Volume: 67-05, Section: B, page: 2499.
500 $a Adviser: Wei-Chiang Shen.
502 $a Thesis (Ph.D.)--University of Southern California, 2005.
520 $a To investigate if the cross-linking of transferrin receptor (TfR) induced by Tf-oligomers can alter the endocytosis of receptor-ligand complexes and hence increases intracellular drug release. Pulse chase and cellular uptake studies have demonstrated that the intracellular retention and degradation of Tf-oligomers were significantly higher than that of monomeric Tf in cultured tumor cells. To further demonstrate that this alteration of TfR-trafficking can facilitate the intracellular release of the drug from the Tf-conjugated form, methotrexate (MTX) was conjugated to Tf-oligomer (Agg-Tf-MTX) or monomeric-Tf (Mono-Tf-MTX). Agg-Tf-MTX was 2- to 3-fold more potent than that of Mono-Tf-MTX in tumor cell lines. In addition, Agg-Tf-MTX was more potent than Mono-Tf-MTX in overcoming the drug resistance. Therefore, Tf-oligomers are potentially effective TfR-targeting carriers for intracellular delivery of anti-cancer drugs.
520 $a Tf-oligomer was also used to investigate the effect that cross-linking of TfR has on intracellular trafficking of the Tf-TfR complex in epithelial cells and to determine whether or not the Tf-oligomer would be a better carrier than monomeric Tf for the oral delivery of protein drugs. The intracellular retention of the Tf-oligomer was higher than that of monomeric Tf. In vivo studies in CF-1 mice showed that the plasma concentrations of Tf from orally administered Tf-oligomer were higher than that of monomeric Tf. Insulin (In), when conjugated to the Tf-oligomer (Agg-Tf-S-S-In), was more effective than monomeric-Tf-In conjugate (Mono-Tf-S-S-In) in reducing blood glucose levels when orally administered to streptozotocin (STZ)-induced diabetic rats. Post oral administration of Agg-Tf-S-S-In, a delayed onset and prolonged hypoglycemic effect were observed. These results demonstrate that the cross-linking of TfR induced by binding of the oligomeric Tf increases the intracellular retention of Tf-TfR complexes in polarized Caco-2 cells and alters the TfR-trafficking which could conceivably have caused the increase of insulin transport across the intestinal barrier when Agg-Tf-S-S-In was administered orally to STZ-induced diabetic rats. The delayed onset and prolonged effect of Agg-Tf-S-S-In in hypoglycemia strongly suggests that the Tf-oligomer can act as a sustained release carrier in the oral delivery of protein and peptide drugs.
590 $a School code: 0208.
650 4 $a Health Sciences, Pharmacy. $3 1017737
650 4 $a Biology, Cell. $3 1017686
650 4 $a Chemistry, Pharmaceutical. $3 550957
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