PEG−peptide conjugates

The remarkable diversity of the self-assembly behavior of PEG−peptides is reviewed, including self-assemblies formed by PEG−peptides with β-sheet and α-helical (coiled-coil) peptide sequences. The modes of self-assembly in solution and in the solid state are discussed. Additionally, applications in bionanotechnology and synthetic materials science are summarized

The efficiency of encapsulation within surface rehydrated polymersomes

The key to the use of polymersomes as effective molecular delivery systems is in the ability to design processing routes that can efficiently encapsulate the molecular payload. We have evaluated various surface rehydration mechanisms for encapsulation, in each case characterizing the morphologies formed using DLS and confocal microscopy as well as determining the encapsulation efficiency for the hydrophilic dye Rhodamine B. In contrast to bulk methods, where the encapsulation efficiencies are low, we find that higher efficiencies can be obtained by the rehydration of thin films. We relate these results to the non-equilibrium mechanisms that underlie vesicle formation and discuss how an understanding of these mechanisms can help optimize encapsulation efficiencies. Our conclusion is that, even considering the good encapsulation efficiency, surface methods are still unsuitable for the massive scale-up needed when applied to commercial “mass market” molecular delivery scenarios. However, targeting more specialized applications for high value ingredients (like pharmaceuticals) might be more feasible

Self-assembly of PEGylated tetra-phenylalanine derivatives: Structural insights from solution and solid state studies

Water soluble fibers of PEGylated tetra-phenylalanine (F4), chemically modified at the N-terminus with the DOTA chelating agent, have been proposed as innovative contrast agent (CA) in Magnetic Resonance Imaging (MRI) upon complexation of the gadolinium ion. An in-depth structural characterization of PEGylated F4-fibers, in presence (DOTA-L6-F4) and in absence of DOTA (L6-F4), is reported in solution and at the solid state, by a multiplicity of techniques including CD, FTIR, NMR, DLS, WAXS and SAXS. This study aims to better understand how the aggregation process influences the performance of nanostructures as MRI CAs. Critical aggregation concentrations for L6-F4 (43 μM) and DOTA-L6-F4 (75 μM) indicate that self-aggregation process occurs in the same concentration range, independently of the presence of the CA. The driving force for the aggregation is the π-stacking between the side chains of the aromatic framework. CD, FTIR and WAXS measurements indicate an antiparallel β-sheet organization of the monomers in the resulting fibers. Moreover, WAXS and FTIR experiments point out that in solution the nanomaterials retain the same morphology and monomer organizations of the solid state, although the addition of the DOTA chelating agent affects the size and the degree of order of the fibers

Supramolecular hydrogels with reverse thermal gelation properties from (oligo)tyrosine containing block copolymers

Novel block copolymers comprising poly(ethylene glycol) (PEG) and an oligo(tyrosine) block were synthesized in different compositions by N-carboxyanhydride (NCA) polymerization. It was shown that PEG2000-Tyr6 undergoes thermoresponsive hydrogelation at a low concentration range of 0.25–3.0 wt % within a temperature range of 25–50 °C. Cryogenic transmission electron microscopy (Cryo-TEM) revealed a continuous network of fibers throughout the hydrogel sample, even at concentrations as low as 0.25 wt %. Circular dichroism (CD) results suggest that better packing of the β-sheet tyrosine block at increasing temperature induces the reverse thermogelation. A preliminary assessment of the potential of the hydrogel for in vitro application confirmed the hydrogel is not cytotoxic, is biodegradable, and produced a sustained release of a small-molecule drug

Self-assembly mechanism for a naphthalene-dipeptide leading to hydrogelation

Suitably functionalized dipeptides have been shown to be effective hydrogelators. The design of the hydrogelators and the mechanism by which hydrogelation occurs are both currently not well understood. Here, we have utilized the hydrolysis of glucono-delta-lactone to gluconic acid as a means of adjusting the pH in a naphthalene-alanylvaline solution allowing the specific targeting of the final pH. In addition, this method allows the assembly process to be characterized. We show that assembly begins as charge is removed from the C-terminus of the dipeptide. The removal of charge allows lateral assembly of the molecules leading to pi-pi stacking (shown by CD) and beta-sheet formation (as shown by IR and X-ray fiber diffraction). This leads to the formation of fibrous structures. Electron microscopy reveals that thin fibers form initially, with low persistence length. Lateral association then occurs to give bundles of fibers with higher persistence length. This results in the initially weak hydrogel becoming stronger with time. The final mechanical properties of the hydrogels are very similar irrespective of the amount of GdL added; rather, the time taken to achieving the final gel is determined by the GdL concentration. However, differences are observed between the networks under strain, implying that the kinetics of assembly do impart different final materials' properties. Overall, this study provides detailed understanding of the assembly process that leads to hydrogelation