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Polymers for Drug Delivery : = Extended Circulation and siRNA Transfection.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Polymers for Drug Delivery :/
其他題名:	Extended Circulation and siRNA Transfection.
作者:	Kierstead, Paul Henry.
面頁冊數:	1 online resource (88 pages)
附註:	Source: Dissertations Abstracts International, Volume: 77-10, Section: B.
Contained By:	Dissertations Abstracts International77-10B.
標題:	Polymer chemistry. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10086000click for full text (PQDT)
ISBN:	9781339591339

Polymers for Drug Delivery : = Extended Circulation and siRNA Transfection.
Kierstead, Paul Henry.

Polymers for Drug Delivery :Extended Circulation and siRNA Transfection. - 1 online resource (88 pages)

Source: Dissertations Abstracts International, Volume: 77-10, Section: B.

Thesis (Ph.D.)--University of California, Berkeley, 2013.

Includes bibliographical references

Polymers are extensively used in the field of drug delivery for many applications. The ability to tailor the physical and in vivo properties of polymers allows them to fulfill many roles in drug delivery. Polymers have found value as both direct drug conjugates and coatings of various other delivery systems such as nanoparticles and liposomes. Here, we investigate both types of systems, polymers as liposome coatings and dendrimers directly bound to siRNA. Chapter 1 presents a brief overview of polymers and macromolecules in the field of drug delivery. Polymeric drug delivery is a very broad and diverse topic, and this chapter mainly addresses areas within the field that relate directly to this dissertation. The history of polymers in drug delivery is presented, and both current capabilities and challenges are discussed. Chapter 2 describes the synthesis of two disterol poly(ethylene glycol) (PEG) conjugates for the incorporation into liposomes. PEG has the ability to stabilize lipid membranes, extend circulation half-life in vivo, and protect lipid membranes from other unfavorable interactions that may occur in biological settings. Commonly, PEG conjugated to a 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) lipid anchor is used to install PEG onto the surface of lipid monolayers and bilayers. However, PEG-DSPE can phase separate in the membrane surface leading to its possible expulsion from the membrane. Additionally, PEG causes a broadening of the phase transition temperature which makes its use in thermally responsive liposomes challenging. We present the synthesis of two disterol PEG molecules and preliminary characterization of their behavior in lipid membranes. Chapter 3 is an evaluation of polymers for extended circulation. We investigate the physical and in vivo properties of a panel of polymers for extended circulation on the surface of liposomes as a model platform, although the conclusions drawn are relevant to many types of drug delivery systems. In this chapter we have synthesized well-defined hydrophilic polymers under controlled polymerization techniques and found that all five polymers investigated have lower intrinsic viscosities to that of PEG under consistent experimental conditions. Furthermore, we show that each polymer extends the circulation half-life of liposomes in mice and rats in comparison to conventional liposomes. We also find an immune response and accelerated blood clearance of poly(2-methyl-2-oxazoline) (PMOX) coated liposomes upon repeated administration and no such response to the other four polymers in the panel. Chapter 4 describes the design, synthesis, and in vitro characterization of pH-responsive, biodegradable dendrimers for the delivery of siRNA. Polycationic materials have been extensively investigated for the delivery of RNAi, however, the inherent toxicity of such materials is a major drawback to their use. We envisioned that by installing multiple amines to a dendrimer core through pH-sensitive hydrazone linkages we would be able to circumvent this roadblock to RNAi delivery. Furthermore, by designing a biodegradable dendrimer with orthogonal sets of functional groups, we were able to install other delivery aids onto the dendrimer periphery. In an in vitro firefly luciferase knockdown assay, polymers displayed decreased toxicity in comparison to other cationic delivery strategies and modest knockdown capabilities. Chapter 5 gives a brief overview of the findings presented in this dissertation followed by a short perspective on the future of polymers in the field of drug delivery.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2023

Mode of access: World Wide Web

ISBN: 9781339591339Subjects--Topical Terms:

3173488
Polymer chemistry.
Subjects--Index Terms:

DendrimerIndex Terms--Genre/Form:

542853
Electronic books.

Polymers for Drug Delivery : = Extended Circulation and siRNA Transfection.
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520 $a Polymers are extensively used in the field of drug delivery for many applications. The ability to tailor the physical and in vivo properties of polymers allows them to fulfill many roles in drug delivery. Polymers have found value as both direct drug conjugates and coatings of various other delivery systems such as nanoparticles and liposomes. Here, we investigate both types of systems, polymers as liposome coatings and dendrimers directly bound to siRNA. Chapter 1 presents a brief overview of polymers and macromolecules in the field of drug delivery. Polymeric drug delivery is a very broad and diverse topic, and this chapter mainly addresses areas within the field that relate directly to this dissertation. The history of polymers in drug delivery is presented, and both current capabilities and challenges are discussed. Chapter 2 describes the synthesis of two disterol poly(ethylene glycol) (PEG) conjugates for the incorporation into liposomes. PEG has the ability to stabilize lipid membranes, extend circulation half-life in vivo, and protect lipid membranes from other unfavorable interactions that may occur in biological settings. Commonly, PEG conjugated to a 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) lipid anchor is used to install PEG onto the surface of lipid monolayers and bilayers. However, PEG-DSPE can phase separate in the membrane surface leading to its possible expulsion from the membrane. Additionally, PEG causes a broadening of the phase transition temperature which makes its use in thermally responsive liposomes challenging. We present the synthesis of two disterol PEG molecules and preliminary characterization of their behavior in lipid membranes. Chapter 3 is an evaluation of polymers for extended circulation. We investigate the physical and in vivo properties of a panel of polymers for extended circulation on the surface of liposomes as a model platform, although the conclusions drawn are relevant to many types of drug delivery systems. In this chapter we have synthesized well-defined hydrophilic polymers under controlled polymerization techniques and found that all five polymers investigated have lower intrinsic viscosities to that of PEG under consistent experimental conditions. Furthermore, we show that each polymer extends the circulation half-life of liposomes in mice and rats in comparison to conventional liposomes. We also find an immune response and accelerated blood clearance of poly(2-methyl-2-oxazoline) (PMOX) coated liposomes upon repeated administration and no such response to the other four polymers in the panel. Chapter 4 describes the design, synthesis, and in vitro characterization of pH-responsive, biodegradable dendrimers for the delivery of siRNA. Polycationic materials have been extensively investigated for the delivery of RNAi, however, the inherent toxicity of such materials is a major drawback to their use. We envisioned that by installing multiple amines to a dendrimer core through pH-sensitive hydrazone linkages we would be able to circumvent this roadblock to RNAi delivery. Furthermore, by designing a biodegradable dendrimer with orthogonal sets of functional groups, we were able to install other delivery aids onto the dendrimer periphery. In an in vitro firefly luciferase knockdown assay, polymers displayed decreased toxicity in comparison to other cationic delivery strategies and modest knockdown capabilities. Chapter 5 gives a brief overview of the findings presented in this dissertation followed by a short perspective on the future of polymers in the field of drug delivery.
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