Photoresponsive polymersomes as smart, triggerable nanocarriers

Cabane, Etienne. Photoresponsive polymersomes as smart, triggerable nanocarriers. 2013, Doctoral Thesis, University of Basel, Faculty of Science.


Official URL: http://edoc.unibas.ch/diss/DissB_10357

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Nowadays, conventional drug delivery systems (DDS), such as oral and parenteral delivery, are the most used administration routes for simple drug molecules. Oral delivery is the most desirable route, especially regarding patient compliance since it is a non-invasive technique, but also regarding cost effectiveness, and ease of use. However, it is clear that the technique is subjected to many hurdles: fragile molecules, such as therapeutic proteins, may lose part of their activity before they can reach the targeted site in the body, because they can be degraded by enzymes or harsh pH conditions, or simply screened out by immunogenic recognition in blood circulation. Additionally, the technique suffers from a lack of control over the release rate, which may be an important drawback, especially regarding toxicity issues.
Therefore, with the increasing complexity of therapeutic agents available to treat a variety of conditions, the need for sophisticated drug delivery systems to improve their liberation to the body is growing. Among the requirements for intelligent DDS, responsiveness is highly desirable as a mean to control pharmacokinetics and pharmacodynamics.
In this thesis, we study the potential of polymeric vesicles obtained from the self-assembly of a photocleavable amphiphilic block copolymer as a light-triggered DDS.
The amphiphilic poly(methyl caprolactone)-ONB-poly(acrylic acid) copolymer (PMCL-ONB-PAA), bearing a photosensitive O-nitrobenzyl linker located as the junction point between the two blocks, is synthesized by the combination of two living polymerization techniques, ring opening polymerization (ROP) and atom transfer radical polymerization (ATRP). The photocleavable linker is modified to serve as initiator for the growth of the polymer segments, in a two-step polymerization. The copolymer is efficiently cleaved upon UV irradiation, whether in solvent or in aqueous solution, yielding two separate polymer segments.
When hydrated, PMCL-ONB-PAA self-assemble into well defined structures, including polymersomes. They are shown to respond in a controlled manner to UV light, via a change in size and morphology. Indeed, loaded polymersomes disintegrate upon UV irradiation, yielding small micellar-like structures, and simultaneously releasing their payload. The versatility of our system is tested both for small molecular weight molecules (Fluorescein and ATTO655 dye), and for proteins (enhanced green fluorescent protein). By varying the UV intensity, the payload is released in a controlled manner, as established by fluorescence spectroscopy and fluorescence correlation spectroscopy. Therefore, these responsive polymer vesicles serve as smart triggerable nanocarriers that can be applied for a variety of payloads, ranging from conventional drug molecules to proteins, enzymes, or DNA.
Advisors:Meier, Wolfgang Peter
Committee Members:Palivan, Cornelia
Faculties and Departments:05 Faculty of Science > Departement Chemie > Former Organization Units Chemistry > Makromolekulare Chemie (Meier)
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:10357
Thesis status:Complete
Number of Pages:109 S.
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edoc DOI:
Last Modified:23 Feb 2018 13:14
Deposited On:07 May 2013 08:04

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