Σύνθεση, Χαρακτηρισμός και Αυτο-Οργάνωση Αποκρινόμενων Συμπολυμερών Πολυ(αιθυλενοξειδίου), Πολυ(ιστιδίνης) και Πολυ(κυστεΐνης) για τον Εγκλωβισμό και την Ελεγχόμενη Αποδέσμευση Φαρμάκων

Postgraduate Thesis uoadl:1320148 282 Read counter

Unit:
Κατεύθυνση Επιστήμη Πολυμερών και Εφαρμογές της
Library of the School of Science
Deposit date:
2016-06-27
Year:
2016
Author:
Βάρλας Σπυρίδων
Supervisors info:
Ερμόλαος Ιατρού Καθηγητής (Επιβλέπων), Μαρίνος Πιτσικάλης Καθηγητής, Γεώργιος Σακελλαρίου Επίκουρος Καθηγητής
Original Title:
Σύνθεση, Χαρακτηρισμός και Αυτο-Οργάνωση Αποκρινόμενων Συμπολυμερών Πολυ(αιθυλενοξειδίου), Πολυ(ιστιδίνης) και Πολυ(κυστεΐνης) για τον Εγκλωβισμό και την Ελεγχόμενη Αποδέσμευση Φαρμάκων
Languages:
Greek
Summary:
In the present research project the synthesis of a series of hybrid polypeptide
copolymers based on poly(L-histidine) (PHis) and poly(L-cysteine) (PCys) was
performed, that possess the ability to respond to external stimuli by altering
their structure. The synthesis of polymers was achieved through a one-step
ring-opening polymerization (ROP) process of the corresponding protected
N-carboxy anhydrides (monomers), using an amine end-functionalized
poly(ethylene oxide) (mPEO-NH2) macroinitiator. High-vacuum techniques were
used for the synthesis of N-carboxy anhydrides of a-amino acids, for the
purification of solvents and for the isolation of well-defined polymers as
well, ensuring the high purity of the system and the absence of impurities that
would result in uncontrolled polymerization processes. These amphiphilic
copolymers of the PEO-b-P(His-co-Cys) type possess the ability to self-assemble
in aqueous media and form micelle-like nanostructures. The outer hydrophilic
corona of the nanostructures was comprised of poly(ethylene oxide) chains,
while the pH-responsive core was based on PHis and PCys. PCys was used as a
hydrophobic component and as a cross-linking agent, forming intermolecular
disulfide bonds that impart extra stability and redox-responsiveness to the
structures. By studying the effect of different cross-linking percentages as
well as the relationship between the hydrophilic and hydrophobic segments,it is
possible to find the optimum polymeric system and draw useful conclusions about
these potential drug nanocarriers. Extensive molecular characterization studies
were conducted in order to confirm the successful synthesis of the polymers and
the desired nanostructures. Also, the synthesis and characterization of
mesoporous silica nanoparticles (MSNs) and the subsequent modification of their
surface with the polymer PEO2K-b-P(His-co-Cys25) were performed, utilizing the
“grafting to” approach. The ultimate goal is to create novel hybrid drug
delivery systems, which will be used for targeted and controlled drug release
applications to cancer cells.
Keywords:
Polypeptides, Ring-Opening Polymerization, Ν-Carboxy Anhydrides, Stimuli-Responsive Polymers, Cross-linked Nanoparticles
Index:
Yes
Number of index pages:
14-19,147-149
Contains images:
Yes
Number of references:
98
Number of pages:
165
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