Tuning the cross-linking density and cross-linker in core cross-linked polymeric micelles and its effects on the particle stability in human blood plasma and mice

Core cross-linked polymeric micelles (CCPMs) are designed to improve the therapeutic profile of hydrophobic drugs, reduce or completely avoid protein corona formation, and offer prolonged circulation times, a prerequisite for passive or active targeting. In this study, we tuned the CCPM stability by using bifunctional or trifunctional cross-linkers and varying the cross-linkable polymer block length. For CCPMs, amphiphilic thiol-reactive polypept(o)ides of polysarcosine-block-poly(S-ethylsulfonyl-l-cysteine) [pSar-b-pCys(SO2Et)] were employed. While the pCys(SO2Et) chain lengths varied from Xn = 17 to 30, bivalent (derivatives of dihydrolipoic acid) and trivalent (sarcosine/cysteine pentapeptide) cross-linkers have been applied. Asymmetrical flow field-flow fraction (AF4) displayed the absence of aggregates in human plasma, yet for non-cross-linked PM and CCPMs cross-linked with dihydrolipoic acid at [pCys(SO2Et)]17, increasing the cross-linking density or the pCys(SO2Et) chain lengths led to stable CCPMs. Interestingly, circulation time and biodistribution in mice of non-cross-linked and bivalently cross-linked CCPMs are comparable, while the trivalent peptide cross-linkers enhance the circulation half-life from 11 to 19 h.Biopharmaceutic

Tuneable pH-regulated supramolecular copolymerisation by mixing mismatched dendritic peptide comonomers

Charged phenylalanine-rich dendritic peptides form highly stable and pH-switchable rod-like supramolecular copolymers, when co-assembled with a matching oppositely charged dendritic comonomer. Here, we demonstrate that by mismatching a strong with a weak β-sheet encoded comonomer, both the stability and the pH-triggered disassembly of the copolymers shifts drastically from pH 4.2 to biologically relevant pH 5.8.</p

Structure to Function in Supramolecular Polymers and Materials

Supramolecular & Biomaterials Chemistr

Structure to Function in Supramolecular Polymers and Materials

Supramolecular & Biomaterials Chemistr

Self-sorting in rodlike micelles of Chiral Bisurea bolaamphiphiles

We have demonstrated the formation of segregated enantiomeric dynamic rods in water, from the self-sorting of chiral trans-1,2-bisureido cyclohexane-based bolaamphiphiles. Fluorescence probes have been used to investigate the self-sorting through forming exciplex and FRET

Synthesis and characterization of water-soluble densely branched glycopolymers

In a one-pot synthesis, highly branched synthetic glycopolymers have been prepared using the 'Strathclyde Methodology' involving a protected galactose monomethacrylate, a branching comonomer (ethylene glycol dimethacrylate or divinylbenzene) and a chain transfer agent (dodecanethiol) with 2,2′-azo-bis-isobutyronitrile as the source of radicals. Branching was confirmed via MALS/SEC and 1H NMR spectroscopy. One attractive feature of the methodology employed is that in a single-step procedure highly branched polymers with molar masses over a range of two orders of magnitude were obtained by fine-tuning the composition of comonomer and chain transfer agent mole feed ratio. Deprotection of the isopropylidene galactose functionalities on the polymers was achieved, leading to water-soluble and potentially bio-compatible synthetic glycopolymers with branched main chain architecture