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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

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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 27, 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. 27 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 27]. 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

2. Banu, Ionut. Modeling and optimization of tubular polymerization reactors : Modélisation et optimisation des réacteurs tubulaires de polymérisation.

Degree: Docteur es, Génie chimique, 2009, Université Claude Bernard – Lyon I

Le but de cette thèse est l’investigation des particularités des problèmes d’optimisation et modélisation des réacteurs tubulaires de polymérisation. La partie originale du travail est divisé en deux sections : la première traitant de l'étude théorique de la modélisation et de l’optimisation des réacteurs tubulaires de polymérisation du méthacrylate de méthyle en solution, et la deuxième, une étude expérimentale et théorique de l'extrusion réactive de L-lactide. Dans la première partie, afin de sélectionner un modèle cinétique représentatif, parmi les modèles publiés pour le processus de polymérisation de MMA, des simulations ont été effectuées en conditions identiques de fonctionnement. Deux algorithmes numériques, l’un basé sur le Principe du Minimum de Pontriaguine et l’autre de type Génétique, ont été comparés pour un problème d'optimisation de complexité moyenne. Les résultats ont montré une robustesse supérieure de l’Algorithme Génétique pour cette catégorie de problèmes. La deuxième partie de la thèse est consacrée à la modélisation et à l’optimisation de l'extrusion réactive du Llactide. Nous avons proposé un modèle cinétique et ses paramètres ont été estimés en utilisant des procédures numériques basées sur les données cinétiques expérimentales. Les expériences d'extrusion réactives ont été exécutées dans les conditions de fonctionnement représentatives. L'écoulement de L-lactide/polylactide dans l'extrudeuse a été caractérisé par la simulation en utilisant un logiciel commercial, LUDOVIC®. Les caractéristiques de la distribution des temps de séjour simulées sont utilisées pour modéliser le processus d'extrusion réactive en utilisant deux approches, un modèle à dispersion axiale et un modèle à base de compartiments, dont les caractéristiques sont déduites des simulations effectuées avec LUDOVIC®. Les résultats de la modélisation du processus sont en bon accord avec des données mesurées en mêmes conditions opératoires.

The aim of this thesis is the investigation of modeling and optimization particularities of tubular polymerization reactors. The original work is divided in two sections, the first treating a modeling and optimization study of tubular reactors for methyl methacrylate polymerization in solution, and the second, an experimental and theoretical study of L-lactide reactive extrusion. In the first section, reactor simulations in similar operating conditions were performed in order to select a representative kinetic model among the published kinetic models for MMA solution polymerization. Two widely used numerical algorithms, one based on Pontryagin’s Minimum Principle and the other a Genetic Algorithm, were compared for an average-complexity optimization problem. The results showed a superior robustness of the Genetic Algorithm for this category of problems. The second part of the thesis deals with the modeling and optimization of L-lactide reactive extrusion. A kinetic model is proposed and its parameters estimated using nonlinear estimation numerical procedures based on experimentally measured…

Advisors/Committee Members: Puaux, Jean-Pierre (thesis director), Bozga, Grigore (thesis director).

Subjects/Keywords: Réacteur tubulaire de polymerisation; Optimisation et modélisation; Réacteur de circulation laminaire; Extrusion réactive de L-lactide; Optimisation des algorithmes génétiques; Polymerization tubular reactor; Modeling and optimization; Laminar flow reactor; L-lactide polymerization kinetics; Polymer flow twin screw extruder; Ludovic flow simulation; Polylactide synthesis by reactive extrusion

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

APA (6th Edition):

Banu, I. (2009). Modeling and optimization of tubular polymerization reactors : Modélisation et optimisation des réacteurs tubulaires de polymérisation. (Doctoral Dissertation). Université Claude Bernard – Lyon I. Retrieved from http://www.theses.fr/2009LYO10121

Chicago Manual of Style (16th Edition):

Banu, Ionut. “Modeling and optimization of tubular polymerization reactors : Modélisation et optimisation des réacteurs tubulaires de polymérisation.” 2009. Doctoral Dissertation, Université Claude Bernard – Lyon I. Accessed October 27, 2020. http://www.theses.fr/2009LYO10121.

MLA Handbook (7th Edition):

Banu, Ionut. “Modeling and optimization of tubular polymerization reactors : Modélisation et optimisation des réacteurs tubulaires de polymérisation.” 2009. Web. 27 Oct 2020.

Vancouver:

Banu I. Modeling and optimization of tubular polymerization reactors : Modélisation et optimisation des réacteurs tubulaires de polymérisation. [Internet] [Doctoral dissertation]. Université Claude Bernard – Lyon I; 2009. [cited 2020 Oct 27]. Available from: http://www.theses.fr/2009LYO10121.

Council of Science Editors:

Banu I. Modeling and optimization of tubular polymerization reactors : Modélisation et optimisation des réacteurs tubulaires de polymérisation. [Doctoral Dissertation]. Université Claude Bernard – Lyon I; 2009. Available from: http://www.theses.fr/2009LYO10121

3. Dorp, van, F. Simulatie van veranderingen in concentraties van voedingselementen rond plantewortels.

Degree: 1977, Landbouwhogeschool Wageningen

Simulation of changes in nutrient concentrations around plant roots. Factors determining nutrient uptake by plant roots can be divided into those influencing root geometry and root growth and those influencing the transport of nutrients to the roots. Experiments were carried out with maize on a nutrient solution in coarse sand and on mixtures of synthetic ion-exchangers onto which nutritive ions were adsorbed. The exchangers were used as a growth medium with characteristics between those of nutrient solution and soil. The results from these experiments and especially from those with nutrient solution were used for computer simulation models (written in CSMP), describing the changes in ion concentration around roots caused by the uptake of nutrients and water by the roots as a function of time over long periods and more in detail over short periods.<p/> Advisors/Committee Members: A. van Diest.

Subjects/Keywords: metabolisme; plantenvoeding; assimilatie; wortels; worteldruk; zuiging; voedingsstoffen; plantenfysiologie; plantenontwikkeling; vloeistoffen (liquids); absorptie; emissie; omloop; modellen; onderzoek; chemische analyse; blootstelling; milieuafbraak; kinetica; ecotoxicologie; Fysiologie van de plantenvoeding; metabolism; plant nutrition; assimilation; roots; root pressure; suction; nutrients; plant physiology; plant development; liquids; absorption; emission; circulation; models; research; chemical analysis; exposure; environmental degradation; kinetics; ecotoxicology; Plant Nutrition Physiology

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

APA (6th Edition):

Dorp, van, F. (1977). Simulatie van veranderingen in concentraties van voedingselementen rond plantewortels. (Doctoral Dissertation). Landbouwhogeschool Wageningen. Retrieved from http://library.wur.nl/WebQuery/wurpubs/71196 ; urn:nbn:nl:ui:32-71196 ; urn:nbn:nl:ui:32-71196 ; http://library.wur.nl/WebQuery/wurpubs/71196

Chicago Manual of Style (16th Edition):

Dorp, van, F. “Simulatie van veranderingen in concentraties van voedingselementen rond plantewortels.” 1977. Doctoral Dissertation, Landbouwhogeschool Wageningen. Accessed October 27, 2020. http://library.wur.nl/WebQuery/wurpubs/71196 ; urn:nbn:nl:ui:32-71196 ; urn:nbn:nl:ui:32-71196 ; http://library.wur.nl/WebQuery/wurpubs/71196.

MLA Handbook (7th Edition):

Dorp, van, F. “Simulatie van veranderingen in concentraties van voedingselementen rond plantewortels.” 1977. Web. 27 Oct 2020.

Vancouver:

Dorp, van F. Simulatie van veranderingen in concentraties van voedingselementen rond plantewortels. [Internet] [Doctoral dissertation]. Landbouwhogeschool Wageningen; 1977. [cited 2020 Oct 27]. Available from: http://library.wur.nl/WebQuery/wurpubs/71196 ; urn:nbn:nl:ui:32-71196 ; urn:nbn:nl:ui:32-71196 ; http://library.wur.nl/WebQuery/wurpubs/71196.

Council of Science Editors:

Dorp, van F. Simulatie van veranderingen in concentraties van voedingselementen rond plantewortels. [Doctoral Dissertation]. Landbouwhogeschool Wageningen; 1977. Available from: http://library.wur.nl/WebQuery/wurpubs/71196 ; urn:nbn:nl:ui:32-71196 ; urn:nbn:nl:ui:32-71196 ; http://library.wur.nl/WebQuery/wurpubs/71196

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