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
A glycosylated 2,2-bis(methylol)propionic acid (bis-MPA) derivative as a versatile glycodendritic building block was synthesized by direct O-glycosylation of benzyl protected bis-MPA with d-glucose pentaacetate. After removal of the benzyl protection group by hydrogenation, the obtained bis-O-glycosylated bis-MPA unit with free carboxyl group was applied for modification of trityl protected chitosan by amidation. The removal of the 6-O-trityl protection group on chitosan backbone under acidic conditions yields acetyl protected glycosylated chitosan that forms gel in water. The acetyl protection group of d-glucose was removed under alkaline conditions to form glycosylated chitosan which is water-soluble at physiological conditions and, thus, it is suitable for further investigation as a potential carrier in drug delivery systems.
COBISS.SI-ID: 5555226
Carboxyl functional groups of poly(L-glutamic acid) (PGlu) were modified with a D-(+)-glucosamine (GlcN) by amidation using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) as a coupling reagent. The coupling reaction was performed in aqueous medium without protection of hydroxyl functional groups of D-(+)-glucosamine. Poly(L-glutamic acid) and GlcN functionalized polyglutamates (P(Glu-GlcN)) were thoroughly characterized by 1D and 2D NMR spectroscopy and SEC-MALS to gain detailed information on their structure, composition and molar mass characteristics. The results reveal successful functionalization with GlcN through the amide bond and also to a minor extent through ester bond formation in position 1 of GlcN. In addition, a ratio between the α- and β-form of glucosamine substituent coupled to polyglutamate repeating units as well as the content of residual dimethoxy triazinyl active ester moiety in the samples were evaluated.
COBISS.SI-ID: 5609754
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
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