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Chemically tailored polymeric micell...

Adams, Monica Lynne.

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Chemically tailored polymeric micelles for drug delivery.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Chemically tailored polymeric micelles for drug delivery./
Author:	Adams, Monica Lynne.
Description:	139 p.
Notes:	Source: Dissertation Abstracts International, Volume: 64-05, Section: B, page: 2201.
Contained By:	Dissertation Abstracts International64-05B.
Subject:	Chemistry, Pharmaceutical. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3089629

Chemically tailored polymeric micelles for drug delivery.
Adams, Monica Lynne.

Chemically tailored polymeric micelles for drug delivery. - 139 p.

Source: Dissertation Abstracts International, Volume: 64-05, Section: B, page: 2201.

Thesis (Ph.D.)--The University of Wisconsin - Madison, 2003.

A principal objective of this research is the rational design of polymeric micelle drug carriers. To improve compatibility between the micelle and the solubilizate, structure-property relationships were explored based on parameters applicable to drug delivery. This work focuses on amphiphilic block copolymers (ABCs) derived from poly(ethylene oxide)-<italic>block</italic>-poly(<smcap> L</smcap>-aspartate), PEO-<italic>b</italic>-p(<smcap>L</smcap>-Asp). PEO-<italic> b</italic>-p(<smcap>L</smcap>-Asp) was chosen as a starting material for several reasons, including possible biocompatibility and the versatility imparted by the poly(carboxylate) block. To aid in building structure-property relationships, a model system has been developed. Within the constraints of the model, we can explore several possibilities for the chemical alteration of ABCs. The model allows variation of the degree of polymerization of the core-forming block, the chemical composition of a spacer group, the composition of an acyl side chain, and the extent of side chain attachment.Subjects--Topical Terms:

550957
Chemistry, Pharmaceutical.

Chemically tailored polymeric micelles for drug delivery.
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035 $a (UnM)AAI3089629
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040 $a UnM $c UnM
100 1 $a Adams, Monica Lynne. $3 1947023
245 1 0 $a Chemically tailored polymeric micelles for drug delivery.
300 $a 139 p.
500 $a Source: Dissertation Abstracts International, Volume: 64-05, Section: B, page: 2201.
500 $a Supervisor: Glen S. Kwon.
502 $a Thesis (Ph.D.)--The University of Wisconsin - Madison, 2003.
520 $a A principal objective of this research is the rational design of polymeric micelle drug carriers. To improve compatibility between the micelle and the solubilizate, structure-property relationships were explored based on parameters applicable to drug delivery. This work focuses on amphiphilic block copolymers (ABCs) derived from poly(ethylene oxide)-<italic>block</italic>-poly(<smcap> L</smcap>-aspartate), PEO-<italic>b</italic>-p(<smcap>L</smcap>-Asp). PEO-<italic> b</italic>-p(<smcap>L</smcap>-Asp) was chosen as a starting material for several reasons, including possible biocompatibility and the versatility imparted by the poly(carboxylate) block. To aid in building structure-property relationships, a model system has been developed. Within the constraints of the model, we can explore several possibilities for the chemical alteration of ABCs. The model allows variation of the degree of polymerization of the core-forming block, the chemical composition of a spacer group, the composition of an acyl side chain, and the extent of side chain attachment.
520 $a To satisfy the structural requirements of the model, an ABC series based on acyl esters of methoxypoly(ethylene oxide)-<italic>block</italic>-poly(<italic> N</italic>-hexyl-<smcap>L</smcap>-aspartamide), PEO-<italic>b</italic>-p(<italic> N</italic>-HA), was prepared. The polymer series was prepared by polymerization of β-benzyl-<smcap>L</smcap>-aspartate-<italic>N</italic>-carboxyanhydride using an amine-terminated initiator, α-methoxy-ω-poly(ethylene oxide). The product was then reacted with 6-amino-1-hexanol to prepare an intermediate containing a hydroxyl-functionalized core-forming block. The hydroxyl groups were then acylated using carboxylic acids or acid anhydrides.
520 $a Above the critical micelle concentration, the PEO-<italic>b</italic>-p(<italic> N</italic>-HA)-acyl esters associate to form nanoscopic structures with core/shell architecture. The basic properties of the micelles were studied as a function of acyl chain length and relative stearate attachment. The polymer series was then used for encapsulation of amphotericin B (AmB), a potent and clinically important antifungal agent.
520 $a Both the length of the acyl side chain and the extent of attachment impact micellar properties. Through “chemical tailoring”, it is possible to alter the aggregation state of encapsulated AmB, which may lead to increased selectively for fungal over mammalian cells. The onset of hemolytic activity is delayed upon AmB encapsulation in PEO-<italic>b</italic>-p(<italic>N</italic>-HA)-acyl ester micelles. In particular, highly substituted poly(ethylene oxide)-<italic> block</italic>-poly(<italic>N</italic>-hexyl-<smcap>L</smcap>-aspartamide)-stearic acid, PEO-<italic>b</italic>-p(HASA), ester micelles resulted in a reduction in the self-aggregation state of AmB and a delay in hemolytic activity. In addition, we have demonstrated retained potency of AmB encapsulated by micelles composed of PEO-<italic>b</italic>-p(HASA) esters in a neutropenic murine model of systemic fungal infection.
590 $a School code: 0262.
650 4 $a Chemistry, Pharmaceutical. $3 550957
650 4 $a Health Sciences, Pharmacy. $3 1017737
650 4 $a Chemistry, Polymer. $3 1018428
690 $a 0491
690 $a 0572
690 $a 0495
710 2 0 $a The University of Wisconsin - Madison. $3 626640
773 0 $t Dissertation Abstracts International $g 64-05B.
790 1 0 $a Kwon, Glen S., $e advisor
790 $a 0262
791 $a Ph.D.
792 $a 2003
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3089629