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Polymeric Micelles for Combination D...

Zeng, San.

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Polymeric Micelles for Combination Drug Delivery in Cancer Therapy.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Polymeric Micelles for Combination Drug Delivery in Cancer Therapy./
作者:	Zeng, San.
面頁冊數:	104 p.
附註:	Source: Dissertation Abstracts International, Volume: 76-09(E), Section: B.
Contained By:	Dissertation Abstracts International76-09B(E).
標題:	Pharmaceutical sciences. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3701466
ISBN:	9781321721256

Polymeric Micelles for Combination Drug Delivery in Cancer Therapy.
Zeng, San.

Polymeric Micelles for Combination Drug Delivery in Cancer Therapy. - 104 p.

Source: Dissertation Abstracts International, Volume: 76-09(E), Section: B.

Thesis (Ph.D.)--The University of Wisconsin - Madison, 2015.

Single small molecule drug therapy is often hindered by drug resistance that develops in cancer cells. Delivery of small interfering RNA (siRNA) to cells via drug delivery systems (DDS) is one effective approach to silence these resistance genes, often successfully re-sensitizing cancer cells to anticancer drugs. Polymeric nanoparticles have been widely explored to protect and deliver siRNA therapeutically. Combination delivery of siRNA and chemotherapeutic drugs is effective against different molecular targets and can increase the sensitization of cancer cells to chemotherapy, thereby overcoming drug resistance.

ISBN: 9781321721256Subjects--Topical Terms:

3173021
Pharmaceutical sciences.

Polymeric Micelles for Combination Drug Delivery in Cancer Therapy.
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245 1 0 $a Polymeric Micelles for Combination Drug Delivery in Cancer Therapy.
300 $a 104 p.
500 $a Source: Dissertation Abstracts International, Volume: 76-09(E), Section: B.
500 $a Adviser: May P. Xiong.
502 $a Thesis (Ph.D.)--The University of Wisconsin - Madison, 2015.
520 $a Single small molecule drug therapy is often hindered by drug resistance that develops in cancer cells. Delivery of small interfering RNA (siRNA) to cells via drug delivery systems (DDS) is one effective approach to silence these resistance genes, often successfully re-sensitizing cancer cells to anticancer drugs. Polymeric nanoparticles have been widely explored to protect and deliver siRNA therapeutically. Combination delivery of siRNA and chemotherapeutic drugs is effective against different molecular targets and can increase the sensitization of cancer cells to chemotherapy, thereby overcoming drug resistance.
520 $a A three layer (trilayer) polymeric micelle system based on the self-association of the triblock copolymer poly(ethylene glycol)-b-poly{N-[N-(2-aminoethyl)-2-aminoethyl] aspartamide}-b-poly(epsilon-caprolactone) (PEG-b-PAsp(DET)-b-PCL) was synthesized to deliver rapamycin (RAP) and siRNA targeting Y-box binding protein-1 (siYB-1). The trilayer micelle is composed of (a) a hydrophilic poly(ethylene glycol) (PEG) block constituting the outer layer to improve pharmacokinetics, (b) an intermediate compartment composed of the cationic poly{2-[(2-aminoethyl)amino] ethyl aspartamide} (PAsp(DET)) segment for interacting with siYB-1, and (c) an inner hydrophobic poly(epsilon-caprolactone) (PCL) compartment for encapsulation of RAP. PEG and PCL are both approved by the FDA, and PAsp(DET) is a non-toxic pH responsive cationic poly(amino acid)-based polymer. We showed that PCL can encapsulate RAP with high loading efficiencies, and PAsp(DET) interacts with siRNA for efficient transfection/knockdown with negligible cytotoxicity. Enhanced therapeutic efficacy of RAP/siYB-1 micelles was demonstrated in cell cultures and in a PC3 xenograft nude mouse model of human prostate cancer.
520 $a We also developed a micelle formulation based on the self-association of PEG-b-PCL to deliver another anticancer drug, citral. Citral is found in the essential oils of many plants. Although it is composed of a random mixture of the two terpenoid isomers geranial (trans-citral) and neral (cis-citral), few studies have directly compared the in vivo antitumor properties of these isomers.
520 $a The antitumor properties of drug formulations were evaluated on the 4T1 xenograft mouse model. Geranial was found to be the more potent isomer of citral and western blot of tumor tissues confirmed that autophagy and not apoptosis was the major mechanism of tumor growth inhibition in p53-null 4T1 cells.
590 $a School code: 0262.
650 4 $a Pharmaceutical sciences. $3 3173021
650 4 $a Biomedical engineering. $3 535387
650 4 $a Oncology. $3 751006
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710 2 $a The University of Wisconsin - Madison. $b Pharmaceutical Sciences. $3 2096793
773 0 $t Dissertation Abstracts International $g 76-09B(E).
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793 $a English
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