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Design of layer-by-layer shaped microparticles for controlled drug delivery.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Design of layer-by-layer shaped microparticles for controlled drug delivery./
Author:	Chen, Jun.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2016,
Description:	222 p.
Notes:	Source: Dissertations Abstracts International, Volume: 78-04, Section: B.
Contained By:	Dissertations Abstracts International78-04B.
Subject:	Polymer chemistry. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10149519
ISBN:	9781369046199

Design of layer-by-layer shaped microparticles for controlled drug delivery.
Chen, Jun.

Design of layer-by-layer shaped microparticles for controlled drug delivery. - Ann Arbor : ProQuest Dissertations & Theses, 2016 - 222 p.

Source: Dissertations Abstracts International, Volume: 78-04, Section: B.

Thesis (Ph.D.)--The University of Alabama at Birmingham, 2016.

This item is not available from ProQuest Dissertations & Theses.

Free drug administration is always associated with several problems, such as poor drug solubility, rapid drug breakdown, fast drug clearance, lack of targeting viability, and inappropriate biodistribution. These problems significantly prevent the accumulation of drugs, specifically to the cancer sites, to achieve high therapy efficacy. The unrestricted diffusion of drugs throughout the whole body also results in severe side effects, such as cytotoxicity and immune responses, to healthy cells which limit the accomplishment of the necessary drug dose to produce efficacious therapy. Therefore, to address these problems, it is urgent to design and develop drug delivery carriers that can protect drugs from degradation, deliver the drugs to the specific diseased sites, and release the drugs with controlled release rates upon external or internal triggers to maintain a high drug therapeutic concentration for a longer time. Although extensive research efforts have aimed to design and develop nanoscale particles as drug delivery carriers in order to improve the drug delivery process and increase the drug efficacy, many of the current existing drug delivery carriers (e.g. conventional pharmaceutical formulations, liposomes and micelles) fail to satisfactorily address these problems. This is due to their inherent stability, low encapsulation efficiency, lack of size and shape varieties, and the difficulties in modification. The dissertation shown here is focused on designing and fabricating novel types of stable hollow polymer microparticles (also known as microcapsules) or porous microparticles of different shapes with high loading capacity through layer-by-layer (LbL) assembly using nontoxic starting materials (e.g. tannic acid (TA), poly(N-vinylpyrrolidone) (PVPON), and poly(methacrylic acid) (PMAA)). All of the followings are demonstrated: synthesis of the microparticles, interaction of microparticles with cancer cells, and the encapsulation and release of different molecules into and from the microparticles. Chapter 2 reports on the design and fabrication of mono-disperse hollow microparticles of spherical, hemispherical, and cubical shapes through LbL assembly using solid silica cores and manganese carbonate (MnCO3) cores as sacrificial templates. Different shaped microparticles in dry state are formed via drying multilayer hydrogen-bonded (PVPON/TA)n microparticles. For instance, hemispherical particles are produced by drying spherical capsules when the deposited number of layers ranges from15 to 20. All hollow microparticles retain their shapes upon rehydration. In vitro cell growth and cytotoxity studies reveal non-cytotoxic properties of (PVPON/TA) microparticles. Both spherical and hemispherical microparticles are internalized by macrophages with the uptake of the hemispherical particles per cell 2-times more efficient. Due to the challenge in the conjugation of drugs on the surface of hemispherical PVPON/TA microparticles, Chapter 3 is focused on developing a way for encapsulating drugs inside hollow TA/PVPON spherical microparticles. In addition, ultrasound has been employed for controlled release of drugs from theranostic agents such as liposomes and microbubbles through mechanical forces and thermal heat. Thus, in this chapter, it also reports the investigation of relationship between the microparticles' ultrasound sensitivity and the particle stiffness, which is regulated by the particle diameter/shell thickness. This chapter also shows that the microparticles' ultrasound sensitivity strongly depends on the particle shell diameter/shell thickness ratio. Based on this relationship, theranostic hollow TA/PVPON microparticles combining ultrasound imaging modality and capability of releasing anticancer drugs upon ultrasound irradiation are designed and synthesized. The released drugs from the microparticles show remarkable cytotoxicity to cancer cells. Besides the design and fabrication of ultrasound responsive hollow microparticles, Chapter 4 demonstrates the use of LbL assembly to design and synthesize a novel type of pH-responsive porous cubical shaped PMAA hydrogel microparticles in a facile way. These hydrogel cubes display a reversible 2-fold change in size while maintaining their shape in response to pH variations. The swelling behaviors of cubic and spherical hydrogel particles and the particle morphology are regulated by the PMAA molecular weight and sacrificial templates porosity. The human cancer cellular viability studies reveal the nontoxic properties of cubic and spherical hydrogels. Finally, pH-triggered loading and release of hydrophobic doxorubicin to and from the cubic hydrogels are shown. Their anticancer effect is also demonstrated. The viability of A549 and HeLa cancer cells are significantly decreased upon interaction with doxorubicin-loaded cubic hydrogels. Chapter 5 demonstrates the development of pH-responsive hollow microparticles composed of PVPON and PMAA interpenetrating network. The permeability of PMAA/PVPON interpenetrating hydrogel microparticles to low molecular weight hydrophilic compounds is also shown in the chapter. In addition, a strategy specifically for decreasing the capsule permeability is accomplished by coating FITC-dextran outside the capsules and changing environmental pH. By using the developed strategy, successful encapsulation of low molecular weight, negatively charged, hydrophilic, compounds and co-encapsulation of different types of small hydrophilic compounds (Alexa532 and Doxorubicin) in PMAA/PVPON interpenetrating hydrogel capsules are achieved at physiological pH.

ISBN: 9781369046199Subjects--Topical Terms:

3173488
Polymer chemistry.
Subjects--Index Terms:

Drug delivery

Design of layer-by-layer shaped microparticles for controlled drug delivery.
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500 $a Source: Dissertations Abstracts International, Volume: 78-04, Section: B.
500 $a Publisher info.: Dissertation/Thesis.
500 $a Advisor: Kharlampieva, Eugenia.
502 $a Thesis (Ph.D.)--The University of Alabama at Birmingham, 2016.
506 $a This item is not available from ProQuest Dissertations & Theses.
506 $a This item must not be added to any third party search indexes.
506 $a This item must not be sold to any third party vendors.
520 $a Free drug administration is always associated with several problems, such as poor drug solubility, rapid drug breakdown, fast drug clearance, lack of targeting viability, and inappropriate biodistribution. These problems significantly prevent the accumulation of drugs, specifically to the cancer sites, to achieve high therapy efficacy. The unrestricted diffusion of drugs throughout the whole body also results in severe side effects, such as cytotoxicity and immune responses, to healthy cells which limit the accomplishment of the necessary drug dose to produce efficacious therapy. Therefore, to address these problems, it is urgent to design and develop drug delivery carriers that can protect drugs from degradation, deliver the drugs to the specific diseased sites, and release the drugs with controlled release rates upon external or internal triggers to maintain a high drug therapeutic concentration for a longer time. Although extensive research efforts have aimed to design and develop nanoscale particles as drug delivery carriers in order to improve the drug delivery process and increase the drug efficacy, many of the current existing drug delivery carriers (e.g. conventional pharmaceutical formulations, liposomes and micelles) fail to satisfactorily address these problems. This is due to their inherent stability, low encapsulation efficiency, lack of size and shape varieties, and the difficulties in modification. The dissertation shown here is focused on designing and fabricating novel types of stable hollow polymer microparticles (also known as microcapsules) or porous microparticles of different shapes with high loading capacity through layer-by-layer (LbL) assembly using nontoxic starting materials (e.g. tannic acid (TA), poly(N-vinylpyrrolidone) (PVPON), and poly(methacrylic acid) (PMAA)). All of the followings are demonstrated: synthesis of the microparticles, interaction of microparticles with cancer cells, and the encapsulation and release of different molecules into and from the microparticles. Chapter 2 reports on the design and fabrication of mono-disperse hollow microparticles of spherical, hemispherical, and cubical shapes through LbL assembly using solid silica cores and manganese carbonate (MnCO3) cores as sacrificial templates. Different shaped microparticles in dry state are formed via drying multilayer hydrogen-bonded (PVPON/TA)n microparticles. For instance, hemispherical particles are produced by drying spherical capsules when the deposited number of layers ranges from15 to 20. All hollow microparticles retain their shapes upon rehydration. In vitro cell growth and cytotoxity studies reveal non-cytotoxic properties of (PVPON/TA) microparticles. Both spherical and hemispherical microparticles are internalized by macrophages with the uptake of the hemispherical particles per cell 2-times more efficient. Due to the challenge in the conjugation of drugs on the surface of hemispherical PVPON/TA microparticles, Chapter 3 is focused on developing a way for encapsulating drugs inside hollow TA/PVPON spherical microparticles. In addition, ultrasound has been employed for controlled release of drugs from theranostic agents such as liposomes and microbubbles through mechanical forces and thermal heat. Thus, in this chapter, it also reports the investigation of relationship between the microparticles' ultrasound sensitivity and the particle stiffness, which is regulated by the particle diameter/shell thickness. This chapter also shows that the microparticles' ultrasound sensitivity strongly depends on the particle shell diameter/shell thickness ratio. Based on this relationship, theranostic hollow TA/PVPON microparticles combining ultrasound imaging modality and capability of releasing anticancer drugs upon ultrasound irradiation are designed and synthesized. The released drugs from the microparticles show remarkable cytotoxicity to cancer cells. Besides the design and fabrication of ultrasound responsive hollow microparticles, Chapter 4 demonstrates the use of LbL assembly to design and synthesize a novel type of pH-responsive porous cubical shaped PMAA hydrogel microparticles in a facile way. These hydrogel cubes display a reversible 2-fold change in size while maintaining their shape in response to pH variations. The swelling behaviors of cubic and spherical hydrogel particles and the particle morphology are regulated by the PMAA molecular weight and sacrificial templates porosity. The human cancer cellular viability studies reveal the nontoxic properties of cubic and spherical hydrogels. Finally, pH-triggered loading and release of hydrophobic doxorubicin to and from the cubic hydrogels are shown. Their anticancer effect is also demonstrated. The viability of A549 and HeLa cancer cells are significantly decreased upon interaction with doxorubicin-loaded cubic hydrogels. Chapter 5 demonstrates the development of pH-responsive hollow microparticles composed of PVPON and PMAA interpenetrating network. The permeability of PMAA/PVPON interpenetrating hydrogel microparticles to low molecular weight hydrophilic compounds is also shown in the chapter. In addition, a strategy specifically for decreasing the capsule permeability is accomplished by coating FITC-dextran outside the capsules and changing environmental pH. By using the developed strategy, successful encapsulation of low molecular weight, negatively charged, hydrophilic, compounds and co-encapsulation of different types of small hydrophilic compounds (Alexa532 and Doxorubicin) in PMAA/PVPON interpenetrating hydrogel capsules are achieved at physiological pH.
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650 4 $a Biomedical engineering. $3 535387
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