Preparation and characterization of the nanocomposite hydrogel based on self-assembly of peptides and poly(vinyl alcohol) for biomedical applications

Supramolekulski samoorganizirajući funkcionalni materijali posjeduju specifična fizikalna i biološka svojstva koja se u nekim slučajevima mogu kontrolirati vanjskim podražajima (temperatura, pH, UV-zračenje). Prepoznati su kao izvrsna platforma za primjenu u raznim područjima, uključujući razvoj senzora, biomaterijala te tkivnog inženjerstva i sustava za dostavu lijekova. Hidro- i organo-gelovi su biokompatibilni, biorazgradivi i netoksični materijali pogodni za primjenu u biomedicini. Kombinacijom supramolekulskih organizacija s različitim anorganskim ili organskim spojevima nastaju nanokompozitni materijali koji imaju poboljšana fizikalna i biološka svojstva. Samoorganizacije organskih molekula male molekulske mase temeljenih na malim peptidima dobro su opisane u literaturi te je pokazana njihova biokompatibilnost. U okviru ovog diplomskog rada, sintetizirani su tripeptidni hidrogelatori Ac-L-Phe-L-Phe-L-Ala-NH2, Ac-L-Phe-L-Phe-L-Ala-OMe i 4-pikolilamidni derivati L-fenilalanin·HCl i D-fenilglicin·HCl. Navedenim gelatorima ispitana su gelirajuća svojstva te je također ispitivano njihovo geliranje dodatkom polimera poli(etilen-glikola) (PEG) i poli(vinil-alkohola) (PVA). Svojstva najboljeg geliranja pokazao je 4-pikolilamidni derivat D-fenilglicina·HCl uz dodatak PVA. Provedeno je preliminarno testiranje kinetike otpuštanja doksorubicina (DOX) iz gela s dodatkom PVA i bez PVA. Rezultati su pokazali da iako PVA utječe na geliranje 4-pikolilamidnog derivata D-fenilglicina·HCl, ubrzava ga i smanjuje kritičnu koncentraciju gelatora, doksorubicin se brže otpušta iz gela koji sadržava PVA.Supramolecular self-organizing functional materials possess specific physical and biological properties that can in some cases be controlled by external stimuli (temperature, pH, UV radiation). They are recognized as an excellent platform for application in various fields, including sensor development, biomaterials, tissue engineering and drug delivery systems. Hydro- and organogels are biocompatible, biodegradable and non-toxic materials that are suitable for biomedical use. Combining supramolecular organizations with various inorganic or organic compounds, nanocomposite materials with improved physical and biological properties are formed. Self-organizations of low molecular weight organic molecules (LMWG) based on small peptides are well described in the literature and their biocompatibility has already been shown. In the framework of this thesis, tripeptide hydrogelators Ac-L-Phe-L-Phe-L-Ala-NH2, Ac-L-Phe-L-Phe-L-Ala-OMe and 4-picolylamide derivatives of L-phenylalanine·HCl and D-phenylglycine·HCl were synthesized. These gels were tested for their gelling properties before and after the addition of polymers of poly (ethylene glycol) (PEG) and poly (vinyl alcohol) (PVA). 4-Picolylamide derivative of D-phenylglycine·HCl with the addition of PVA showed the best gelling properties. Preliminary testing of the release of doxorubicin (DOX) from the gel with the addition of PVA and without PVA has been tested. The results indicate that PVA affects the gelling of 4-picolylamide derivative of D-phenylglycine·HCl, accelerating it and reducing the critical concentration of the gelator while doxorubicin is released more rapidly from the gel containing PVA