Hyperbranched PEI with Various Oligosaccharide Architectures: Synthesis, Characterization, ATP Complexation, and Cellular Uptake Properties

Abstract

We present a rapid synthetic method for the development of hyperbranched PEIs decorated with different oligosaccharide architectures as carrier systems (CS) for drugs and bioactive molecules for in vitro and in vivo experiments. Reductive amination of hyperbranched PEI with readily available oligosaccharides results in sugar functionalized PEI cores with oligosaccharide shells of different densities. These core-shell architectures were characterized by NMR spectroscopy, elemental analysis, SLS, DLS, IR, and polyelectrolyte titration experiments. ATP complexation of theses polycations was examined by isothermal titration calorimetry to evaluate the binding energy and ATP/CS complexation ratios under physiological conditions. In vitro experiments showed an enhanced cellular uptake of ATP/CS complexes compared to those of the free ATP molecules. The results arise to initiate further noncovalent complexation studies of pharmacologically relevant molecules that may lead to the development of therapeutics based on this polymeric delivery platform.

Cast adhesive polyelectrolyte complex particle films of unmodified or maltose-modified poly(ethyleneimine) and cellulose sulphate: fabrication, film stability and retarded release of zoledronate

“…Branched poly(ethyleneimine) with molecular weights of 1.3 kg/Mol (PEI-1.3 K), 25 kg/Mol (PEI-25 K) and of 750 kg/Mol (PEI-750 K) (gift of BASF, Ludwigshafen) and cellulose sulphate (CS, 2.900 kg/Mol, degree of substitution DS = 2.9-2.8, ACROS) were dissolved to 0.002 M solutions related to their monomer units. PEI-M-25 K was synthesized according to a protocol published therein [11]. Macromolecular structures are given in the Figure 1.…”

“…Therefore, PEC systems composed of PEI-M are expected to provide an enhanced biocompatibility compared to unmodified PEI. PEI-M systems have been established in the last years as potent carrier systems for model drugs ATP [11,12], si-RNA and DNA [9,13] and show a benign interaction to different relevant cell types [9,10]. Herein, zoledronate (ZOL) was chosen, since it is to date an established BP of choice for the systemic therapy of osteoporosis [14] and multiple myeloma [15], which is more potent compared to PAM.…”

Structural analysis of the curing of epoxy thermosets crosslinked with hyperbranched poly(ethyleneimine)s

“…The batch synthesis of hyperbranched polyethyleneimines in aqueous solution has been reported [36], leading to polymers with an amine ratio of approximately 1:2:1 determined by NMR. However, commercial polymers may have different amine ratios, about 1:1:1 [36], and with very narrow polymer distribution [37], indicating that the synthetic procedure may be different such as slow monomer addition [31] or else have been synthesized with the addition of a core molecule to control the polymer distribution, as reported in the patent literature [38].…”

Glycopolymers of Various Architectures—More than Mimicking Nature

“…[80] The most prominent representatives of the hyperbranched glycopolymers are hyperbranched polyethylene imines (PEI) decorated with different mono-, di-, and oligosaccharide units, preferably used as carrier systems for poly-, oligo-, and mononucleotide acids. [81][82][83] The introduction of the various saccharide units on PEI surfaces is preferentially achieved by reductive amination or the reaction of thioisocyanate-modified saccharide units with the amino groups of PEI. First approaches in thin layer technology were also successfully undertaken to use hyperbranched glycopolymers as bio-active supports for cell adhesion [84] or for enantiospecific separation of D/L-mixtures by chiral polyelectrolyte multilayers.…”