Synthesis and high throughput/high content (HT/HC) analysis of a combinatorial library of polymeric micelles

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Title: Synthesis and high throughput/high content (HT/HC) analysis of a combinatorial library of polymeric micelles
Author: Barth, Silvia
Other contributor: Helsingin yliopisto, Farmasian tiedekunta
University of Helsinki, Faculty of Pharmacy
Helsingfors universitet, Farmaceutiska fakulteten
Publisher: Helsingfors universitet
Date: 2014
Language: eng
Thesis level: master's thesis
Discipline: Biofarmaci
Abstract: The impact of nanoparticulate drug carriers, especially polymeric micelles, is growing continuously. However, their drug delivery properties in vivo are difficult to predict. In this thesis, the approach of screening a combinatorial library of nano carriers for their drug delivery properties in a high throughput/high content (HT/HC) manner was tested. The library consisted of self-assembling polymeric micelles, using the amphiphilic polymer DSPE-PEG2000. The physicochemical characterization of micelles was focused on size, shape and stability, tested by various methodologies. The micelles were labeled with the fluorescence dye Alexa568 and the combinatorial character was based on labeling with two different Cell Penetrating Peptides (CPP), RGD and transactivator of transcription (TAT), in three molar ratios each. The cytotoxicity concentration ranges and micelle uptake were tested in the ARPE-19 cell line. Intracellular localization was observed by confocal fluorescence microscopy. Quantitative HCS imaging analysis was performed by image cytometry, whereas only the parameter 'micelles spots per cell' was analyzed exemplarily. The quantitative HCS results were not clear and pointed to insufficient optimization of experimental and analytical parameters. The results suggest that HCS could be a suitable method to analyze a nanoparticulate library for its drug delivery properties, requiring careful optimization of experimental parameters. However, the careful characterization of the micellar library is a critical factor in planning and understanding biological experiments.
Subject: DSPE-PEG2000
KeywoHigh Content Screening
polymeric micelles
combinatorial library

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