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Design challenges in nanoparticle-ba...

Mullen, Douglas Gurnett.

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Design challenges in nanoparticle-based platforms: Implications for targeted drug delivery systems.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Design challenges in nanoparticle-based platforms: Implications for targeted drug delivery systems./
Author:	Mullen, Douglas Gurnett.
Description:	190 p.
Notes:	Source: Dissertation Abstracts International, Volume: 71-11, Section: B, page: .
Contained By:	Dissertation Abstracts International71-11B.
Subject:	Chemistry, Polymer. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3429464
ISBN:	9781124285122

Design challenges in nanoparticle-based platforms: Implications for targeted drug delivery systems.
Mullen, Douglas Gurnett.

Design challenges in nanoparticle-based platforms: Implications for targeted drug delivery systems. - 190 p.

Source: Dissertation Abstracts International, Volume: 71-11, Section: B, page: .

Thesis (Ph.D.)--University of Michigan, 2010.

Characterization and control of heterogeneous distributions of nanoparticle-ligand components are major design challenges for nanoparticle-based platforms. This dissertation begins with an examination of poly(amidoamine) (PAMAM) dendrimer-based targeted delivery platform. A folic acid targeted modular platform was developed to target human epithelial cancer cells. Although active targeting was observed in vitro, active targeting was not found in vivo using a mouse tumor model. A major flaw of this platform design was that it did not provide for characterization or control of the component distribution.

ISBN: 9781124285122Subjects--Topical Terms:

1018428
Chemistry, Polymer.

Design challenges in nanoparticle-based platforms: Implications for targeted drug delivery systems.
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100 1 $a Mullen, Douglas Gurnett. $3 1671128
245 1 0 $a Design challenges in nanoparticle-based platforms: Implications for targeted drug delivery systems.
300 $a 190 p.
500 $a Source: Dissertation Abstracts International, Volume: 71-11, Section: B, page: .
500 $a Adviser: Mark M. Banaszak Holl.
502 $a Thesis (Ph.D.)--University of Michigan, 2010.
520 $a Characterization and control of heterogeneous distributions of nanoparticle-ligand components are major design challenges for nanoparticle-based platforms. This dissertation begins with an examination of poly(amidoamine) (PAMAM) dendrimer-based targeted delivery platform. A folic acid targeted modular platform was developed to target human epithelial cancer cells. Although active targeting was observed in vitro, active targeting was not found in vivo using a mouse tumor model. A major flaw of this platform design was that it did not provide for characterization or control of the component distribution.
520 $a Motivated by the problems experienced with the modular design, the actual composition of nanoparticle-ligand distributions were examined using a model dendrimer-ligand system. High Pressure Liquid Chromatography (HPLC) resolved the distribution of components in samples with mean ligand/dendrimer ratios ranging from 0.4 to 13. A peak fitting analysis enabled the quantification of the component distribution. Quantified distributions were found to be significantly more heterogeneous than commonly expected and standard analytical parameters, namely the mean ligand/nanoparticle ratio, failed to adequately represent the component heterogeneity. The distribution of components was also found to be sensitive to particle modifications that preceded the ligand conjugation.
520 $a With the knowledge gained from this detailed distribution analysis, a new platform design was developed to provide a system with dramatically improved control over the number of components and with improved batch reproducibility. Using semi-preparative HPLC, individual dendrimer-ligand components were isolated. The isolated dendrimer with precise numbers of ligands were characterized by NMR and analytical HPLC. In total, nine different dendrimer-ligand components were obtained with degrees of purity ≥80%. This system has the potential to serve as a platform to which a precise number of functional molecules can be attached and has the potential to dramatically improve platform efficacy.
520 $a An additional investigation of reproducibility challenges for current dendrimer-based platform designs is also described. The mass transport quality during the partial acetylation reaction of the dendrimer was found to have a major impact on subsequent dendrimer-ligand distributions that cannot be detected by standard analytical techniques. Consequently, this reaction should be eliminated from the platform design. Finally, optimized protocols for purification and characterization of PAMAM dendrimer were detailed.
590 $a School code: 0127.
650 4 $a Chemistry, Polymer. $3 1018428
650 4 $a Engineering, Biomedical. $3 1017684
650 4 $a Engineering, Materials Science. $3 1017759
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690 $a 0541
690 $a 0794
710 2 $a University of Michigan. $3 777416
773 0 $t Dissertation Abstracts International $g 71-11B.
790 1 0 $a Holl, Mark M. Banaszak, $e advisor
790 $a 0127
791 $a Ph.D.
792 $a 2010
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3429464