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Self-Encapsulation of Vaccine Antigens in PLGA Microparticles and Microneedles.

Record Type:	Language materials, manuscript : Monograph/item
Title/Author:	Self-Encapsulation of Vaccine Antigens in PLGA Microparticles and Microneedles./
Author:	Mazzara, John Maxwell.
Description:	1 online resource (188 pages)
Notes:	Source: Dissertation Abstracts International, Volume: 78-07(E), Section: B.
Contained By:	Dissertation Abstracts International78-07B(E).
Subject:	Pharmaceutical sciences. -
Online resource:	click for full text (PQDT)
ISBN:	9781369588941

Self-Encapsulation of Vaccine Antigens in PLGA Microparticles and Microneedles.
Mazzara, John Maxwell.

Self-Encapsulation of Vaccine Antigens in PLGA Microparticles and Microneedles. - 1 online resource (188 pages)

Source: Dissertation Abstracts International, Volume: 78-07(E), Section: B.

Thesis (Ph.D.)

Includes bibliographical references

There is an urgent need to reduce reliance on hypodermic injections for many protein-based therapies. Alternative approaches include developing controlled release formulations, which reduce dosing frequencies, and utilizing alternative delivery devices, such as microneedles. This thesis explores the development of controlled release microparticles made of poly(lactic- co-glycolic acid) (PLGA) that encapsulate stable/active proteins. These microparticles are then delivered via novel microneedle patches. This work has great implications for improving the utility and coverage of protein-based vaccines.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2018

Mode of access: World Wide Web

ISBN: 9781369588941Subjects--Topical Terms:

1180569
Pharmaceutical sciences.
Index Terms--Genre/Form:

554714
Electronic books.

Self-Encapsulation of Vaccine Antigens in PLGA Microparticles and Microneedles.
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100 1 $a Mazzara, John Maxwell. $3 1184120
245 1 0 $a Self-Encapsulation of Vaccine Antigens in PLGA Microparticles and Microneedles.
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300 $a 1 online resource (188 pages)
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500 $a Source: Dissertation Abstracts International, Volume: 78-07(E), Section: B.
500 $a Adviser: Steven P. Schwendeman.
502 $a Thesis (Ph.D.) $c University of Michigan $d 2016.
504 $a Includes bibliographical references
520 $a There is an urgent need to reduce reliance on hypodermic injections for many protein-based therapies. Alternative approaches include developing controlled release formulations, which reduce dosing frequencies, and utilizing alternative delivery devices, such as microneedles. This thesis explores the development of controlled release microparticles made of poly(lactic- co-glycolic acid) (PLGA) that encapsulate stable/active proteins. These microparticles are then delivered via novel microneedle patches. This work has great implications for improving the utility and coverage of protein-based vaccines.
520 $a PLGA microparticles are loaded with protein through a novel approach termed active self-healing encapsulation (ASE). This method loads proteins after microparticle fabrication, thus preventing protein exposure to a variety of stresses. ASE utilizes a protein trapping agent (Alhydrogel), along with the self-healing of microparticle surface pores to sequester and trap proteins inside the microparticles. The self-healing phenomenon was explored in detail, and was determined to be a viscoelastic response of the polymer to high surface tension when above the glass-transition temperature (Tg). The healing kinetics followed expected Williams-Landel-Ferry behavior, and Arrhenius plots generated activation energies consistent with polymeric creep. A mathematical model to predict healing times is also presented.
520 $a The ASE technique afforded high loading (1.64% w/w) and encapsulation efficiencies up to 91% for the model protein Ovalbumin. In vitro controlled release was shown to be biphasic, with an initial release of soluble protein followed by a delayed release of Alhydrogel-complexed protein over the course of two months. Furthermore, a bulk batch of microparticles can be used to load many different proteins without needing to reformulate unique batches.
520 $a A process was also designed to deliver protein-loaded microparticles via a microneedle patch. Microneedle patches can be easily self-applied, are easy to store/dispose, and are generally preferred by patients over traditional hypodermic needles. These patches, made of a dissolvable material, successfully delivered microparticles intradermally where they began antigen release. In animal models these patches generated a robust immune response that was as good as or better than conventional administration techniques.
520 $a This thesis lays the ground work for a versatile system for delivering protein-based vaccines with reduced dosing requirements or limited need for hypodermic injections.
533 $a Electronic reproduction. $b Ann Arbor, Mich. : $c ProQuest, $d 2018
538 $a Mode of access: World Wide Web
650 4 $a Pharmaceutical sciences. $3 1180569
655 7 $a Electronic books. $2 local $3 554714
690 $a 0572
710 2 $a ProQuest Information and Learning Co. $3 1178819
710 2 $a University of Michigan. $b Pharmaceutical Sciences. $3 1184121
773 0 $t Dissertation Abstracts International $g 78-07B(E).
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10391684 $z click for full text (PQDT)