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Elastic forces give rise to unusual phase transformations in polyelectrolyte gels: A Raman microscopy study
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry. (Pharmaceutical Physical Chemistry)
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Solid State Physics.ORCID iD: 0000-0003-2759-7356
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry. (Pharmaceutical Physical Chemistry)
(English)Manuscript (preprint) (Other academic)
National Category
Pharmaceutical Sciences
Research subject
Pharmaceutical Physical Chemistry; Pharmaceutical Science; Pharmaceutics
Identifiers
URN: urn:nbn:se:uu:diva-472817OAI: oai:DiVA.org:uu-472817DiVA, id: diva2:1652294
Available from: 2022-04-18 Created: 2022-04-18 Last updated: 2022-04-18
In thesis
1. Microgels as drug delivery vehicles: loading and release of amphiphilic drugs
Open this publication in new window or tab >>Microgels as drug delivery vehicles: loading and release of amphiphilic drugs
2022 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Polyelectrolyte microgels are used as delivery vehicles for amphiphilic drugs in, e.g., treatments of liver cancer by a method called trans-arterial chemoembolization. The thesis deals with fundamental properties of such delivery systems related to the self-assembling properties of the drug molecules and their interaction with the charged polymer network of the microgel. The main objective was to establish mechanistic models describing the loading and release of drugs under relevant conditions. For that purpose experimental techniques providing thermodynamic, compositional and microstructural information were used to elucidate how the kinetics depend on the stability of the drug self-assemblies and the volume response of the microgels. Micromanipulator-assisted microscopy studies showed that negatively charged microgels phase separated during loading and release of cationic amphiphilic drugs. At intermediate loading levels the drug aggregates and part of the network formed a collapsed phase coexisting with a swollen, drug-lean phase. In particular, during release in a medium of physiological ionic strength, the drug-lean phase formed a depletion layer (shell) surrounding a drug-rich core. Investigations of a series of drugs with different molecular architectures showed that the drug release rate was determined mainly by the stability of the drug aggregates in the core and the diffusive mass transport of drug molecules through the shell. Detailed studies of polyacrylate microgels interacting with amitriptyline hydrochloride showed that swelling of the shell network greatly influenced the release rate. Furthermore, experiments with a specially constructed microscopy cell was used to establish that the collapsed and swollen phases could coexist in equilibrium, and that the swelling of the network in the swollen phase depended on the proportion between them when present in the same microgel. The latter effect was related to the elastic coupling between the phases. Confocal Raman microscopy was employed to demonstrate, for the first time, the related elastic effect, that the concentration of amitriptyline in the swollen phase decreased with increasing proportion of the collapsed phase. Small-angle X-ray scattering showed that the collapsed phase had a disordered microstructure of drug micelles with ellipsoidal shape. The aggregation number increased with increasing concentration of drug in the microgel, most likely by incorporating the uncharged base form. By providing detailed information about thermodynamic properties and microstructures, the results of the thesis provide a basis for rational design of microgel drug delivery systems.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2022. p. 61
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 312
Keywords
microgel, amphiphilic drug, phase separation, micropipette, Raman microscopy, controlled release, drug delivery, SAXS
National Category
Pharmaceutical Sciences
Research subject
Pharmaceutical Physical Chemistry
Identifiers
urn:nbn:se:uu:diva-472818 (URN)978-91-513-1502-7 (ISBN)
Public defence
2022-06-14, Room A1:111a, BMC, Husargatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2022-05-17 Created: 2022-04-18 Last updated: 2022-06-15

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Edvinsson, Tomas

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