Biodegradable polymersomes for drug delivery : circulation kinetics and biodistribution, modulated drug delivery and cellular uptake


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Lee, Jung Seok (2011) Biodegradable polymersomes for drug delivery : circulation kinetics and biodistribution, modulated drug delivery and cellular uptake. thesis.

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Abstract:In this thesis, the development and characterization of biodegradable and/or enzymetriggered destabilizable polymersomes (Ps) for controlled and targeted drug delivery are presented. In Chapter 1, a general introduction, the aim of the study and structure of the thesis are given. Scientific background information on the criteria for the formation of Ps and methods for their characterization are discussed in Chapter 2. In this chapter, also the recent progress on and challenges for the design of biodegradable and/or stimulisensitive Ps in the field of drug delivery are reviewed. In Chapter 3, the preparation and characterizations of Oregon Green® 488 Labeled Paclitaxel (Flutax) loaded biodegradable Ps based on methoxy poly(ethylene glycol)-b-poly(D,L-lactide) (mPEGPDLLA), methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-PCL) or a mixture of the block copolymers is described. Hydrogel-containing Ps (Hs, hydrosomes) are reported in Chapter 4. Results of time-resolved fluorescence as well as the timeresolved fluorescence anisotropy of fluorescein isothicyanate labeled poly(Nisopropylacrylamide) FITC-N in Ps as a function of temperature are given in Chapter 5.
Novel peptide-containing Ps (Ps (pep)) have been developed and characterized in
Chapter 6. A peptide sequence, Phe-Gly-Leu-Phe-Gly (FGLFG) was introduced in
between mPEG and PDLLA (mPEG-pep-PDLLA) and the Ps can be destabilized by the
presence of lysosomal enzyme cathepsin B (Cath B) as a result of the enzymatic
hydrolysis of the peptide linker. The surface of Ps (pep) was further modified by coupling with anti-epidermal growth factor receptor antibody (abEGFR) to enhance their interaction with cells. In Chapter 7, the results of in vivo studies of Ps prepared from PEG-PDLLA in tumor-bearing mice are compared with those of stealth liposomes. The effects of the surface charge of the Ps on circulation kinetics, organ distribution and tumor accumulation were evaluated.
Item Type:Thesis
Faculty:
Science and Technology (TNW)
Research Group:
Link to this item:http://purl.utwente.nl/publications/77086
Official URL:http://dx.doi.org/10.3990/1.9789036531887
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