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Modular approach toward multifunctio...

Gindy, Marian E.

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Modular approach toward multifunctional nanoparticles for integrated drug delivery, targeting, and diagnostics: Synthetic methods and practical applications.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Modular approach toward multifunctional nanoparticles for integrated drug delivery, targeting, and diagnostics: Synthetic methods and practical applications./
作者:	Gindy, Marian E.
面頁冊數:	286 p.
附註:	Advisers: Robert K. Prud'homme; Athanassios Z. Panagiotopoulos.
Contained By:	Dissertation Abstracts International69-03B.
標題:	Chemistry, Pharmaceutical. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3305759
ISBN:	9780549524410

Modular approach toward multifunctional nanoparticles for integrated drug delivery, targeting, and diagnostics: Synthetic methods and practical applications.
Gindy, Marian E.

Modular approach toward multifunctional nanoparticles for integrated drug delivery, targeting, and diagnostics: Synthetic methods and practical applications. - 286 p.

Advisers: Robert K. Prud'homme; Athanassios Z. Panagiotopoulos.

Thesis (Ph.D.)--Princeton University, 2008.

This thesis details methods for the controlled synthesis and characterization of multifunctional nanoparticulate carriers combining the capacity to deliver organic and inorganic drugs and/or imaging contrast agents. The combination of properties characteristic of each component into a single integrated system is expected to result in more effective therapeutic regimens, earlier and more accurate disease detection, and non-invasive assessment of responses to therapies. The common requirements of such systems are biocompatibility of components, high payload of encapsulated agents, control of particle size and component compositions, and the ability to selectively functionalize the carrier surfaces for ligand-directed delivery.

ISBN: 9780549524410Subjects--Topical Terms:

550957
Chemistry, Pharmaceutical.

Modular approach toward multifunctional nanoparticles for integrated drug delivery, targeting, and diagnostics: Synthetic methods and practical applications.
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245 1 0 $a Modular approach toward multifunctional nanoparticles for integrated drug delivery, targeting, and diagnostics: Synthetic methods and practical applications.
300 $a 286 p.
500 $a Advisers: Robert K. Prud'homme; Athanassios Z. Panagiotopoulos.
500 $a Source: Dissertation Abstracts International, Volume: 69-03, Section: B, page: 1779.
502 $a Thesis (Ph.D.)--Princeton University, 2008.
520 $a This thesis details methods for the controlled synthesis and characterization of multifunctional nanoparticulate carriers combining the capacity to deliver organic and inorganic drugs and/or imaging contrast agents. The combination of properties characteristic of each component into a single integrated system is expected to result in more effective therapeutic regimens, earlier and more accurate disease detection, and non-invasive assessment of responses to therapies. The common requirements of such systems are biocompatibility of components, high payload of encapsulated agents, control of particle size and component compositions, and the ability to selectively functionalize the carrier surfaces for ligand-directed delivery.
520 $a Using block copolymer-directed self-assembly and the Flash NanoPrecipitation technique, a diffusion-controlled precipitation process, materials of various physical properties could be reliably integrated into a single particle of complex composition. The modular design strategy undertaken in this dissertation was predicated on a combinatorial approach and exemplified through the preparation of nanoparticles which could independently or in combination encapsulate (i) hydrophobic small molecule organics, (ii) pre-formed inorganic nanocrystalline colloids, and (iii) hydrophilic macromolecular compounds, permitting encapsulation of therapeutic compounds irrespective of their water solubilities. In addition, methods for the controlled functionalization of particle surfaces with disease-specific macromolecular targeting ligands were also developed, yielding carriers that could be specifically delivered via a synergistic combination of passive (particle size control) and active (ligand-directed) targeting strategies.
520 $a In particular, using gold colloids as a model system, block copolymer-stabilized composite nanoparticles (CNPs) were prepared via Flash NanoPrecipitation. Parameters controlling physical properties of the particles were identified experimentally and compared to predictions from a model of CNP formation in the diffusion-limited colloid aggregation regime. In addition, the combined incorporation of nanocrystals with drugs into a single construct was also demonstrated, enabling simultaneous drug delivery and medical imaging. In all cases, uniform particles were produced with tunable sizes between 75 nm and 275 nm, narrow particle size distributions, high encapsulation efficiencies, independently specified component compositions, and long term stability.
520 $a Because the particles assemble spontaneously from solution by simultaneous desolvation of components, explicit chemical functionalization of nanocrystals is not required, and the method can be applied to a variety of nanocrystals that lack appropriate conjugate surface chemistry. Based on this capacity, two practical applications of CNP constructs were developed. Composite particles of iron oxide nanocrystals were prepared as agents for magnetic resonance imaging contrast enhancement. In addition, the design of a novel construct based on the co-encapsulation of organic photosensitizers and inorganic upconverting phosphor nanocrystals for improved photodynamic therapy was outlined.
520 $a Finally, Monte Carlo simulations were used to study the solution phase behavior of linear amphiphilic multiblock copolymers. Depending on the chain architecture, characterized by block size (n) and number of block units per chain (m), the copolymers were found to undergo microscopic phase separation into roughly spherical core/shell-type aggregates for m/n ratios less than a critical value and first order precipitation otherwise. The enthalpic driving force of phase change was found to universally scale with chain length and was independent of the existence of a true phase transition. Qualitative agreement was found between experimentally observed physical property changes and phase transitions predicted by the simulations. Finally, critical parameters and microstructure characteristics of macroscopic and microscopic phase separating systems, respectively, were also determined.
520 $a In summary, the methods developed in this dissertation provide a comprehensive and highly flexible platform for the preparation of multifunctional carriers that can be customized to suit the specific disease target, imaging or diagnostic format, or treatment modality.
590 $a School code: 0181.
650 4 $a Chemistry, Pharmaceutical. $3 550957
650 4 $a Chemistry, Polymer. $3 1018428
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790 1 0 $a Panagiotopoulos, Athanassios Z., $e advisor
790 1 0 $a Prud'homme, Robert K., $e advisor
791 $a Ph.D.
792 $a 2008
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