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Functional polymers and dendrimers i...

University of California, Berkeley.

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Functional polymers and dendrimers in therapeutics.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Functional polymers and dendrimers in therapeutics./
作者:	Guillaudeu, Steven Joseph.
面頁冊數:	134 p.
附註:	Adviser: Jean M. J. Frechet.
Contained By:	Dissertation Abstracts International69-09B.
標題:	Chemistry, Organic. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3331617
ISBN:	9780549836858

Functional polymers and dendrimers in therapeutics.
Guillaudeu, Steven Joseph.

Functional polymers and dendrimers in therapeutics. - 134 p.

Adviser: Jean M. J. Frechet.

Thesis (Ph.D.)--University of California, Berkeley, 2008.

PEGylated dendrimers, macromolecules in which polyethylene glycol chains are attached to a dendrimer core, are among the newest class of polymers that have been explored for the delivery of chemotherapeutics. These polymers are unimolecular species in solution that have a core-shell architecture reminiscent of supramolecular micelles and liposomes which have both found great use for the delivery of therapeutics. These branched polymers are capable of greatly increasing the solubility of hydrophobic therapeutics. Additionally, their in vivo circulation and distribution characteristics make them fantastic vehicles for the imaging and treatment of solid tumors.

ISBN: 9780549836858Subjects--Topical Terms:

516206
Chemistry, Organic.

Functional polymers and dendrimers in therapeutics.
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245 1 0 $a Functional polymers and dendrimers in therapeutics.
300 $a 134 p.
500 $a Adviser: Jean M. J. Frechet.
500 $a Source: Dissertation Abstracts International, Volume: 69-09, Section: B, page: 5409.
502 $a Thesis (Ph.D.)--University of California, Berkeley, 2008.
520 $a PEGylated dendrimers, macromolecules in which polyethylene glycol chains are attached to a dendrimer core, are among the newest class of polymers that have been explored for the delivery of chemotherapeutics. These polymers are unimolecular species in solution that have a core-shell architecture reminiscent of supramolecular micelles and liposomes which have both found great use for the delivery of therapeutics. These branched polymers are capable of greatly increasing the solubility of hydrophobic therapeutics. Additionally, their in vivo circulation and distribution characteristics make them fantastic vehicles for the imaging and treatment of solid tumors.
520 $a An introduction to polymer-drug delivery vehicles is presented in Chapter 1. The unique characteristics of polymer drug delivery, as opposed to conventional chemotherapy, are discussed. Then, a discussion of the various architectures and macromolecular classes available for chemotherapeutic drug delivery provides rationale for the use of PEGylated dendrimers in particular is presented.
520 $a In Chapter 2, the syntheses of a large variety of PEGylated ester dendrimers with multiple copies of many different functionalities present on the dendrimers are presented. These are useful for the attachment of biologically relevant moieties such as drugs and imaging agents. The dendrimers chosen are based on the biodegradable polyester backbone. Functionality on these dendrimers includes ketones, carboxylates, phenols, alcohols, and alkynes. The in vitro and in vivo characteristics of the phenolic dendrimer and the carboxylate dendrimer, modified to contain the chemotherapeutic Doxorubicin, are discussed.
520 $a In Chapter 3, a PEGylated lysine dendrimer is conjugated to doxorubicin and used in the effective delivery of the drug to treat the C26 murine colon carcinoma. A detailed description of the synthesis and solution phase characteristics of the PEGylated dendrimer with different drug loadings, up to &sim;20 wt%, is given. The PEGylated lysine dendrimer was evaluated in vivo both with and without drug, and in both cases low levels of polymer concentration in healthy tissue were observed. Favorably long circulation times and accumulation in the tumor tissue by the enhanced permeability and retention effect led to a successful therapeutic regimen using only one dose of the polymer therapeutic.
520 $a In order to expand the utility of PEGylated dendrimers for chemotherapy, we have begun to look at other drugs beside doxorubicin. In particular, many hydroxyl-containing drugs such as paclitaxel and the camptothecins may benefit from delivery using PEGylated dendrimers. In Chapter 4, the attachment of camptothecin to a PEGylated lysine dendrimer and the initial investigations into the carriers solution phase properties and toxicity are discussed. Additionally, initial progress into various acid-sensitive release strategies for hydroxyl-terminated drugs is presented. It was determined that attachment of prodrugs of camptothecin, modified to contain a ketone, through the acid sensitive hydrazone bond may prove useful in future therapeutic settings.
590 $a School code: 0028.
650 4 $a Chemistry, Organic. $3 516206
650 4 $a Chemistry, Pharmaceutical. $3 550957
650 4 $a Chemistry, Polymer. $3 1018428
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791 $a Ph.D.
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