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Abstract: The derivatization of the polysaccharide dextran with N-protected amino acids (Boc-L-Phenylalanine, BocGlycine, Boc-L-Cysteine, and Boc-L-Cysteine-S-Trt) and peptides (Boc-L-DiPhenylalanine, Boc DiGlycine, and 2,5-diketopiperazine) as the basis for biomaterial preparation is presented in this Doctoral Dissertation. Such prepared dextran derivatives are intended to mimic the proteoglycan complex (PGs), one of the most important structural and functional biomacromolecules in the extracellular matrix (ECM) of tissue. Nowadays, developments in biomaterials are focusing increasingly on the preparation and use of biomimetic molecular structures to achieve positive results in tissue engineering (TE) and drug delivery. Designing and synthesizing these biomimetic materials, however, requires sophisticated chemical and material preparation methods, knowledge that is, currently, unexplored. In this work, we developed a suitable procedure for dextran derivatization, and investigated the most optimal reaction or deprotection conditions (temperature and time) and isolation/purification methods. The structures of the obtained BocPhe-Dex, BocGly-Dex, BocCys-Dex, and BocSTLC-Dex were analyzed with FTIR, NMR, SEC-MALS, and EA. The results showed that dextran derivatization was successful in all cases except in the case of dextran derivatization with BocCys. Investigation of the effect of the derivatization conditions and purification on the stability, purity, and other important chemical and physical properties of the obtained product, showed that the temperature and time of derivatization do not have a bigger effect on the products' properties, while the purification method, on the other hand, has. Its effect is visible in the product's purity and mass yields of products prepared under the same reaction conditions. Derivatization of dextran with peptides (Boc-L-DiPhenylalanine, BocDiGlycine, and 2,5-diketopiperazine) was performed using the CDI coupling agent or Amberlite-IR 120 as a catalyst. The products were analyzed with FTIR and 1H and 13C NMR. The results showed successful dextran derivatization in the case of BocDiPhenylalanine and BocDiGlycine, while, in the case of 2,5-diketopiperazine, a reaction covalent bond with the dextran was not confirmed. BocPhe-Dex and BocSTLC-Dex were selected as the most optimal amino acid-dextran derivatives for further preparation of 3D formulations in the shape of nanoparticles (NPs). Nanoparticles were prepared with the emulsion/solvent evaporation method from the obtained BocPhe-Dex and BocSTLC-Dex products (prepared in the first stage of this Doctoral Dissertation). SEM analysis showed that the prepared NPs were homogeneous and nicely spherical, with an average dry diameter of 325 ± 118 nm in the case of BocSTLC-Dex, and 1039 ± 382 nm in the case of NPs prepared from BocPhe-Dex. All the prepared NPs retained their proper spherical shape and stability during the acidic treatment, and so confirmed their potential for further functionalization and applications for drug delivery. The BocSTLC-Dex NPs were also evaluated with cell viability tests, which showed that the prepared NPs were not cytotoxic, one of the most important characteristics for the drug delivery applications of NPs. This work serves as a basis for further studies on the derivatization of polysaccharides with amino acids and peptides, and their application in tissue engineering or drug delivery.
Keywords: Amino Acid-Dextran derivatives, Peptide-Dextran derivatives, Proteoglycan complex, 3D formulation, Nanoparticles, Drug delivery
Published in DKUM: 18.10.2024; Views: 0; Downloads: 46
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Abstract: V diplomski nalogi predstavljamo pripravo poroznih polimernih materialov s tehniko sintranja poli(metil metakrilatnih) (PMMA) zrn. Nov polimerni material smo sintetizirali s polimerizacijo v vmesnih prostorih med zrni. Sintrana zrna so nam tako služila kot nosilec, prek katerega smo nanesli monomerno mešanico in jo polimelizirali. Prelit nosilec je bilo nato treba očistiti v ustreznem topilu, ki je omogočalo odstranitev sintranih zrn iz na novo sintetiziranega materiala in s tem nastanek porozne strukture. Pri izboru topila smo bili zato omejeni na dva pogoja, tj. izbrano topilo je moralo dobro raztapljati poli(metil metakrilatna) (PMMA) zrna, medtem ko nanešenega polimeliziranega materiala ni smelo topiti. Za pripravo primerno sintranih nosilcev je bilo najprej treba določiti optimalne pogoje (temperaturo in čas sintranja), pri katerih se zrna najmočneje in najbolje spojijo. Kot najbolj optimalno se je izkazalo sintranje pri 180 °C 24 h. Za dosego optimalnih rezultatov je bilo v postopek priprave sintranih nosilcev treba vključiti še predhodno stresanje zrn, ki je omogočilo zmanjšanje praznin med nasutimi zrni in s tem boljše stikanje samih zrn, kar je pripomoglo k večji končni poroznosti na novo pripravljenega polimernega materiala. Z zgoraj opisano tehniko smo tako pripravili dva porozna polimerna materiala. To sta alifatski uretanski diakrilat (AUD) in bisfenol A glicerolat (1-glicerol/fenol) dimetakrilat (Bis GMA). Oba sta nastala s porozno strukturo, sestavljeno iz primarnih por, ki jih medsebojno povezujejo manjše, povezovalne pore. Primarne pore zasedajo mesta, kjer se je pred čiščenjem novega polimera nahajal sintran nosilec, povezovalne pore pa so se izoblikovale na stičnih mestih sintranih zrn.
Keywords: poli(metil metakrilat), porozni polimeri, polimerni nosilci, sintranje, polimerizacija
Published in DKUM: 22.09.2014; Views: 2379; Downloads: 279
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