Invited lecture at the 10th International Symposium on Polymer Therapeutics, From laboratory to clinical practice, 19th-21th May 2014, Centro de Investigación Príncipe Felipe, Valencia, Spain.
B.04 Guest lecture
COBISS.SI-ID: 5523994PhD thesis of Peter Perdih encompassed the design of new synthetic pathways for preparation of novel polymers with various architectures as potential carriers for drug delivery with focus on high-molecular weight protein/peptide drugs, i.e. biopharmaceuticals. Synthesized graft copolymers of chitosan-graft-poly(L-glutamate) with varying length of peptide grafts, were, in combination with trimethylchitosan, successfully used for preparation of nanoparticles with high association efficiency and final loading of a granulocyte-colony stimulating factor protein drug. The effect of the grafted peptide length, the ratio of the protein drug and the amount of added trimethylchitosan were studied. Synthesized nanoparticles show narrow distribution of size with average diameter of 240-320 nm. Nanoparticles were thermally stable over longer period of time. On the other hand, pH stability studies show that nanoparticles are unstable at pH values above the isoelectric point of the protein drug which was desired for this type of drug delivery system. The results obtained during his PhD were published in two scientific papers (Cellulose and Molecules) and he is also a coauthor of an European patent application.
D.09 Tutoring for postgraduate students
COBISS.SI-ID: 276099584In this presentation the synthesis, characterization and application of novel non-toxic, biodegradable and biocompatible polymer drug carriers of different architecture based on various combinations of chitosan, synthetic polypeptides and dendritic polymers will be presented, i.e. poly(ester-amide) dendrimers synthesized from AB2 adduct of 2,2-bis(hydroxymethyl) propanoic acid and glycine, alkyl-modified poly(sodium glutamates) synthesized by ring-opening polymerization of N-carboxyanhydrides and subsequent hydrophobic post-polymerization modification and chitosan-graft-poly(sodium-L-glutamate), prepared by grafting polypeptide grafts from chitosan backbone. Our goal was to prepare drug delivery systems with improved properties for delivery of poorly water-soluble low molecular-weight active pharmaceutical ingredients in the form of solid dispersions or for oral delivery of high molecular-weight protein/peptide drugs (biopharmaceuticals) in the form of nanoparticles, prepared by polyelectrolyte complexation method.
B.04 Guest lecture
COBISS.SI-ID: 5595418The invention relates to novel polymers, which exhibit improved association with protein drugs and enable the formation of nanoparticles with high protein loading.
F.08 Development and manufacture of a prototype
COBISS.SI-ID: 5465882The negatively charged, water-soluble, hydrophobically modified poly(sodium glutamate)s, containing different amounts of randomly distributed alkyl grafts, were synthesized. First, poly(γ-benzyl-L-glutamate) was prepared by ring-opening polymerization of the corresponding N-carboxyanhydride. Then the benzyl ester groups were partially aminolysed with octylamine. The degree of aminolysis was controlled by changing the mole ratio of octylamine to benzyl glutamate repeat units. The polypeptide degradation during aminolysis was to a large extent prevented by the addition of 2-hydroxypyridine as a bifunctional catalyst. The degree of alkylation was determined by 1H NMR and the molecular structure by MALDI-TOF MS. After removal of the remaining benzyl groups, the alkyl modified poly(sodium glutamate)s (P(Glu-oa)) were obtained and, together with the oppositely charged N,N,N-trimethyl chitosan, used for the preparation of nanoparticles of recombinant granulocyte colony-stimulating factor (GCSF) protein by polyelectrolyte complexation method. It was observed that, beside electrostatic interaction, the hydrophobic grafts on poly(sodium glutamate)s significantly contribute to the association efficiency with GCSF protein. The addition of N,N,N-trimethyl chitosan solution to the dispersion of GCSF/P(Glu-oa) complexes resulted in formation of well-defined nanoparticles with high association efficiency and high final protein loading.
B.06 Other
COBISS.SI-ID: 5596442