The negatively charged, water-soluble, hydrophobically modified poly(sodium glutamate)s containing different amounts of alkyl grafts were synthesized. First, poly(γ-benzyl-L-glutamate) was prepared by ring-opening polymerization of the corresponding N-carboxyanhydride, which was in the next step aminolysed with octylamine. After removal of the remaining benzyl protective groups, the alkyl-modified poly(sodium glutamate)s [P(Glu-oa)] were obtained and, together with the oppositely charged N,N,N-trimethyl chitosan (TMC), used for the preparation of nanoparticles (NPs) of a recombinant granulocyte colony-stimulating factor (GCSF) protein by polyelectrolyte complexation method. It is observed that, beside electrostatic interaction, the hydrophobic grafts on poly(sodium glutamate)s significantly contribute to association efficiency (AE) with GCSF protein. The addition of TMC solution to the dispersion of GCSF/P(Glu-oa) complexes results in formation of much more defined NPs with high AE and final protein loading.
COBISS.SI-ID: 5530906
In this manuscript we have designed a synthetic approach for the preparation of a series of chitosan-graft-poly(L-glutamate) copolymers with different lengths of poly(L-glutamate) grafts. First, organosulfonic chitosan salt, soluble in DMSO, was prepared in order to effectively initiate ringo-pening polymerization of γ-benzyl-L-glutamate N-carboxyanhydride.The chitosan-graft-poly(γ-benzyl-L-glutamate) copolymers were fully deprotected by applying tetrabutylammonium hydroxide. The molar mass characteristics and the chemical composition of graft copolymers with various lengths of polypeptide grafts were determined by SEC-MALS, FT-IR and various NMR spectroscopic techniques. The synthesized copolymers were further used in combination with trimethyl chitosan for the preparation of nanoparticles (NPs) of a recombinant granulocyte colonystimulating factor (GCSF). The suspensions of NPs with typical average diameter of 200–300 nm were obtained with polydispersity index values below 0.26. The achieved loading efficiency was up to 95% and the final loading of GCSF protein in NPs was up to 45%. The time, temperature and pH stability of NPs was also studied.
COBISS.SI-ID: 5522714
Water-soluble, biodegradable, and biocompatible poly(ester-amide) dendrimers with hydroxyl functional groups are synthesized from previously prepared AB2 adduct of 2,2-bis(hydroxymethyl) propanoic acid (bis-MPA) and glycine as a repeating unit. Two esterification procedures using different coupling reagent/catalyst systems (DCC/DPTS or EDC/DMAP) are studied with respect to efficiency, ease of products purification, and quality of the final products. Both procedures have their own benefits and drawbacks, depending on dendrimer generation. The synthesized poly(ester-amide) dendrimers as well as commercially available bis-MPA dendrimers, poly(ester-amide) hyperbranched polymer, and poly(vinyl alcohol) are used for preparation of solid dispersions of sulfonylurea antidiabetic drug glimepiride to improve its poor water-solubility. In vitro dissolution studies show in comparison with pure glimepiride in crystalline or amorphous form, to the same extent improved glimepiride solubility for solid dispersions based on dendritic polymers, but not for poly(vinyl alcohol). The amount of glimepiride complexed with both dendrimer types increases with dendrimer generation.
COBISS.SI-ID: 5548826