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Polymeric Nanocarriers for the Delivery of Ionizable Therapeutics: Formulation, Internal Structure, and Large-Scale Process Development.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Polymeric Nanocarriers for the Delivery of Ionizable Therapeutics: Formulation, Internal Structure, and Large-Scale Process Development./
Author:	Ristroph, Kurt David.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2021,
Description:	300 p.
Notes:	Source: Dissertations Abstracts International, Volume: 83-04, Section: B.
Contained By:	Dissertations Abstracts International83-04B.
Subject:	Pharmaceutical sciences. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28548392
ISBN:	9798471107090

Polymeric Nanocarriers for the Delivery of Ionizable Therapeutics: Formulation, Internal Structure, and Large-Scale Process Development.
Ristroph, Kurt David.

Polymeric Nanocarriers for the Delivery of Ionizable Therapeutics: Formulation, Internal Structure, and Large-Scale Process Development. - Ann Arbor : ProQuest Dissertations & Theses, 2021 - 300 p.

Source: Dissertations Abstracts International, Volume: 83-04, Section: B.

Thesis (Ph.D.)--Princeton University, 2021.

This item must not be sold to any third party vendors.

The efficient encapsulation of water-soluble biopharmaceuticals ('biologics') into micro- and nano-delivery vehicles is essential for their therapeutic success as antibiotics, vaccines, and gene therapies. Encapsulation of biologics using liposomes or water-in-oil-in-water emulsions have struggled to achieve commercial success because they suffer from inefficient encapsulation and poor scalability. The few commercial successes rely heavily on the drug's specific chemical properties; therefore, the lessons from one formulation are rarely generalizable to other biologics. This variability has hampered the field's ability to develop methodologies for encapsulating biologics. The result is a patchwork approach for formulation and scaleup that suffers from inefficiencies in (i) independently controlling targets such as vehicle size and charge, payload ratios and loading, drug release rate, and encapsulation efficiency, and (ii) processing at scale. Changing a single target midway through formulation can require restarting the process development.This dissertation describes work aimed at improving the pipeline from drug substance (unformulated biologic) to drug product (formulation at scale) through the development of a nanoformulation strategy applicable across several classes of therapeutics that allows broad control over the targets described above. This research examines (1) the combination of solubility engineering and particle formulation techniques to efficiently encapsulate biologics and water-soluble small molecule drugs into nanocarriers with high loadings; (2) the design and manipulation of internal liquid crystalline structures to control drug release; and (3) the colloidal dynamics in these systems to develop novel large-scale nanocarrier processing operations. Therapeutics formulated and used herein include ecumicin (an antitubercular peptide), polymyxin B (an antimicrobial peptide), and OZ439 and lumefantrine (antimalarial small molecules).

ISBN: 9798471107090Subjects--Topical Terms:

3173021
Pharmaceutical sciences.
Subjects--Index Terms:

Polymeric nanocarriers

Polymeric Nanocarriers for the Delivery of Ionizable Therapeutics: Formulation, Internal Structure, and Large-Scale Process Development.
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100 1 $a Ristroph, Kurt David. $3 3683644
245 1 0 $a Polymeric Nanocarriers for the Delivery of Ionizable Therapeutics: Formulation, Internal Structure, and Large-Scale Process Development.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2021
300 $a 300 p.
500 $a Source: Dissertations Abstracts International, Volume: 83-04, Section: B.
500 $a Advisor: Prud'homme, Robert Krafft.
502 $a Thesis (Ph.D.)--Princeton University, 2021.
506 $a This item must not be sold to any third party vendors.
520 $a The efficient encapsulation of water-soluble biopharmaceuticals ('biologics') into micro- and nano-delivery vehicles is essential for their therapeutic success as antibiotics, vaccines, and gene therapies. Encapsulation of biologics using liposomes or water-in-oil-in-water emulsions have struggled to achieve commercial success because they suffer from inefficient encapsulation and poor scalability. The few commercial successes rely heavily on the drug's specific chemical properties; therefore, the lessons from one formulation are rarely generalizable to other biologics. This variability has hampered the field's ability to develop methodologies for encapsulating biologics. The result is a patchwork approach for formulation and scaleup that suffers from inefficiencies in (i) independently controlling targets such as vehicle size and charge, payload ratios and loading, drug release rate, and encapsulation efficiency, and (ii) processing at scale. Changing a single target midway through formulation can require restarting the process development.This dissertation describes work aimed at improving the pipeline from drug substance (unformulated biologic) to drug product (formulation at scale) through the development of a nanoformulation strategy applicable across several classes of therapeutics that allows broad control over the targets described above. This research examines (1) the combination of solubility engineering and particle formulation techniques to efficiently encapsulate biologics and water-soluble small molecule drugs into nanocarriers with high loadings; (2) the design and manipulation of internal liquid crystalline structures to control drug release; and (3) the colloidal dynamics in these systems to develop novel large-scale nanocarrier processing operations. Therapeutics formulated and used herein include ecumicin (an antitubercular peptide), polymyxin B (an antimicrobial peptide), and OZ439 and lumefantrine (antimalarial small molecules).
590 $a School code: 0181.
650 4 $a Pharmaceutical sciences. $3 3173021
650 4 $a Chemical engineering. $3 560457
650 4 $a Materials science. $3 543314
653 $a Polymeric nanocarriers
653 $a Ionizable therapeutics
653 $a Process development
653 $a Formulation
653 $a Internal structure
690 $a 0572
690 $a 0542
690 $a 0794
710 2 $a Princeton University. $b Chemical and Biological Engineering. $3 2094012
773 0 $t Dissertations Abstracts International $g 83-04B.
790 $a 0181
791 $a Ph.D.
792 $a 2021
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28548392