Advanced search options

Advanced Search Options 🞨

Browse by author name (“Author name starts with…”).

Find ETDs with:

in
/  
in
/  
in
/  
in

Written in Published in Earliest date Latest date

Sorted by

Results per page:

You searched for id:"uu:oai:dspace.library.uu.nl:1874/399869". One record found.

Search Limiters

Last 2 Years | English Only

No search limiters apply to these results.

▼ Search Limiters

1. Liu, Yanna. Polymeric Micelles Loaded with mTHPC for Photodynamic Therapy: from synthesis to in vitro and in vivo evaluation.

Degree: 2020, University Utrecht

m-Tetra(hydroxyphenyl)chlorin (mTHPC) is one of the most potent second generation photosensitizers (PSs), clinically used for photodynamic therapy (PDT) of head and neck squamous cell carcinomas. However, the very hydrophobic character of mTHPC encounters problems similar to that of many other PSs and chemotherapeutic drugs, such as low-water solubility, aggregation in aqueous media, and limited tumor specificity. These lead to difficulties of formulation and administration, suboptimal PDT efficacy, and off-target effects, such as skin sensitivity. Nanoparticulate drug delivery systems for mTHPC provide opportunities to tackle these drawbacks, by their capacity to encapsulate hydrophobic PS to yield aqueous dispersions facilitating its administration and increase accumulation of the PS at targeted tissues via passive targeting (i.e. enhanced permeability and retention (EPR) effect) and/or active targeting strategies. Among different drug delivery systems, polymeric micelles, composed of a hydrophilic stealth corona (most commonly based on PEG) for ensuring long circulation and colloidal stability, and a hydrophobic core for accommodating hydrophobic drugs, are suitable and attractive systems for delivery of mTHPC. In this thesis, different polymeric micelles based on poly(ε-caprolactone)-b-poly(ethylene glycol) (PCL-PEG) block copolymers were prepared to load mTHPC with the aim to develop suitable micellar systems for targeted delivery of mTHPC. The stability of polymeric micelles and the retention of mTHPC in the micelles are essential for improved pharmacokinetics, selective biodistribution and consequently effective PDT. Therefore, this thesis reports on studies of in vitro stability, in vivo circulation kinetics, and biodistribution of different micellar mTHPC formulations. Further emphasis is given on the synthesis and characterization of a variety of amphiphilic block copolymers based on PEG (as hydrophilic block) and PCL (as hydrophobic blocks). To modulate and tailor the properties of the hydrophobic block, CL is copolymerized with carbonates functionalized by aromatic groups (Chapter 4) and crosslinkable dithiolanes (Chapters 5 and 6), respectively, to design π-π stacked and core crosslinked micelles with the aim to improve the stability of the micelles in the circulation and the retention of mTHPC in the core of the micelles. In conclusion, the research presented in this thesis explores the possibility of preparation of stable PCL-PEG based polymeric micelles with small sizes as targeted delivery systems of mTHPC for PDT. We focused on the stabilization of small micelles exploiting chemical (disulfide crosslinking) and physical crosslinking (crystallization or π-π stacking), thus improving the retention of PS in vivo by tailoring the compositions and architectures of amphiphilic block copolymers using different strategies. The results of the pharmacokinetics, including circulation kinetics and biodistribution of these different stabilized micelles and their loaded mTHPC, provide important scientific… Advisors/Committee Members: Hennink, W.E., Nostrum, C.F. van, Oliveira, S..

Subjects/Keywords: Polymer synthesis; polymeric micelles; in vitro stability; circulation kinetics; biodistribution

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Liu, Y. (2020). Polymeric Micelles Loaded with mTHPC for Photodynamic Therapy: from synthesis to in vitro and in vivo evaluation. (Doctoral Dissertation). University Utrecht. Retrieved from https://dspace.library.uu.nl/handle/1874/399869 ; URN:NBN:NL:UI:10-1874-399869 ; 10.33540/324 ; 1874/399869 ; urn:isbn:9789463807944 ; URN:NBN:NL:UI:10-1874-399869 ; https://dspace.library.uu.nl/handle/1874/399869

Chicago Manual of Style (16th Edition):

Liu, Yanna. “Polymeric Micelles Loaded with mTHPC for Photodynamic Therapy: from synthesis to in vitro and in vivo evaluation.” 2020. Doctoral Dissertation, University Utrecht. Accessed October 25, 2020. https://dspace.library.uu.nl/handle/1874/399869 ; URN:NBN:NL:UI:10-1874-399869 ; 10.33540/324 ; 1874/399869 ; urn:isbn:9789463807944 ; URN:NBN:NL:UI:10-1874-399869 ; https://dspace.library.uu.nl/handle/1874/399869.

MLA Handbook (7th Edition):

Liu, Yanna. “Polymeric Micelles Loaded with mTHPC for Photodynamic Therapy: from synthesis to in vitro and in vivo evaluation.” 2020. Web. 25 Oct 2020.

Vancouver:

Liu Y. Polymeric Micelles Loaded with mTHPC for Photodynamic Therapy: from synthesis to in vitro and in vivo evaluation. [Internet] [Doctoral dissertation]. University Utrecht; 2020. [cited 2020 Oct 25]. Available from: https://dspace.library.uu.nl/handle/1874/399869 ; URN:NBN:NL:UI:10-1874-399869 ; 10.33540/324 ; 1874/399869 ; urn:isbn:9789463807944 ; URN:NBN:NL:UI:10-1874-399869 ; https://dspace.library.uu.nl/handle/1874/399869.

Council of Science Editors:

Liu Y. Polymeric Micelles Loaded with mTHPC for Photodynamic Therapy: from synthesis to in vitro and in vivo evaluation. [Doctoral Dissertation]. University Utrecht; 2020. Available from: https://dspace.library.uu.nl/handle/1874/399869 ; URN:NBN:NL:UI:10-1874-399869 ; 10.33540/324 ; 1874/399869 ; urn:isbn:9789463807944 ; URN:NBN:NL:UI:10-1874-399869 ; https://dspace.library.uu.nl/handle/1874/399869

.