Bulk and nanoscale polypeptide based polyelectrolyte complexes

Abstract

Polyelectrolyte complexes (PECs) formed using polypeptides have great potential for developing new self-assembled materials, in particular for the development of drug and gene delivery vehicles. This review discusses the latest advancements in PECs formed using polypeptides as the polyanion and/or the polycation in both polyelectrolyte complexes that form bulk materials and block copolymer complexes that form nanoscale assemblies such as PEC micelles and other self-assembled structures. We highlight the importance of secondary structure formation between homogeneous polypeptide complexes, which, unlike PECs formed using other polymers, introduces additional intermolecular interactions in the form of hydrogen bonding, which may influence precipitation over coacervation. However, we still include heterogeneous complexes consisting of polypeptides and other polymers such as nucleic acids, sugars, and other synthetic polyelectrolytes. Special attention is given to complexes formed using nucleic acids as polyanions and polypeptides as polycations and their potential for delivery applications.

Keywords: Coacervates; Micelle; Polyelectrolytes; Polypeptides; Self-assembly.

Figure 1

Solid and liquid polyelectrolyte complexes using pLys and pGlu. Solid complexes (left image) are characterized by their amorphous shape are formed using L-pLys(PLK) and L-pGlu(PLE). Coacervates are formed using L-pLys (PLK) and racemic pGlu(P(D,L)E) and are characterized by their spherical shape. Scale bar 25 microns. FTIR spectra of the amide one region of both complexes are shown below images. Both complexes have a peak around 1642–1646 cm⁻¹ indicative of a random coil configuration, and another peak at another peak at 1563 cm⁻¹ corresponding to the glutamic acid side chain. Only solid complexes have peaks at 1610 and 1678 cm⁻¹ indicative of β-strand structure. Reproduced from Hoffmann et al. with permission from the Royal Society of Chemistry. [37]

Figure 2

Schematic illustration for preparation and intracellular trafficking of cross-linked polyplexes with pH and disulfide reduction dual intracellular environment-sensitivity for improved gene delivery. Reprinted with permission from Sanjoh et al. Copyright 2012 American Chemical Society.

Figure 3

Preparation of polypeptide complex coacervates with encapsulated proteins. Reproduced with permission from Black et al. [59]

Figure 4

TEM images of PICs at 25C and 1mg/mL (scale bar 100nm) with PEG fraction of (a) 12.1 % (b) 11.1% and (c)10.0%. Image reproduced with permission from Wibowo et al.[70]

Figure 5

Cryogenic phase-contrast transmission electron microscopic image of Nano-PICsomes after crosslinking obtained at a total polymer concentration of mg ml⁻¹. Arrow indicates vesicle walls. Image reproduced with permission from Anraku et al.[119]