Authors:	Fach, Lars Matthias
Title:	Protein-based nanoparticles for drug delivery applications
Online publication date:	5-Jun-2018
Year of first publication:	2018
Language:	english
Abstract:	By the year 2030, the World Health Organization expects the total number of new cancer cases will grow to 21.7 million worldwide. Today, almost every seventh death is caused by cancer. Nanocarriers are very similar in size and shape to biological nanostructures and have already shown very promising results for drug delivery in cancer therapy. They increase drug solubility as well as bioavailability and reduce toxic side effects that often occur during chemotherapy as they selectively accumulate in the tumor tissue by an enhanced permeability and retention effect. Proteins show low toxicity and high biodegradability. Therefore, they can be a valuable source for highly defined biomaterials for the preparation of nanocarriers. In this work, a novel method for the preparation of nanoparticles based on the assembly of surface modified proteins that are soluble in organic solvents is presented. Particle preparation for hydrophobic payloads is carried out by an oil-in-water nanoemulsion technique without the need of additional cross-linking steps or denaturation for stabilization. The necessary lipophilic switch of the protein material is obtained by high surface PEGylation whilst preserving the native structure of the proteins. This system is first presented in detail for lysozyme, as model protein and doxorubicin as hydrophobic model drug. After a comprehensive analysis of the obtained protein-polymer conjugate, empty and doxorubicin-loaded nanoparticles are prepared with a diameter around 100 nm that still present the enzymatic activity of the native protein. The particles are stable in physiological buffers and a release of the therapeutic payload into cancer cells is only observed after a time dependent cellular uptake. Later, proteins in a broad range of molecular weights are used as starting material to exemplify that this preparation procedure has the potential to be transferred to any protein of choice. Here, also the influence of the polymer chain length on the solubility in organic solvents for the different protein sizes is presented. Additionally, the hydrophobic payload of the particles is exchanged by curcumin to present the high variability of this carrier system leading to particles with diameters below 200 nm. Furthermore, a water-in-oil-in-water nanoemulsion technique is used to prepare protein-based nanoparticles with an entrapped hydrophilic payload. This shows that the presented nanocarrier system has also high potential for the delivery of hydrophilic payloads, e.g. nucleic acids.
DDC:	540 Chemie 540 Chemistry and allied sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 09 Chemie, Pharmazie u. Geowissensch.
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-4433
URN:	urn:nbn:de:hebis:77-diss-1000020232
Version:	Original work
Publication type:	Dissertation
License:	In Copyright
Information on rights of use:	https://rightsstatements.org/vocab/InC/1.0/
Extent:	171 Seiten
Appears in collections:	JGU-Publikationen