RESUMO
The complexation of polyelectrolytes with other oppositely charged structures gives rise to a great variety of functional materials with potential applications in a wide spectrum of technological fields. Depending on the assembly conditions, polyelectrolyte complexes can acquire different macroscopic configurations such as dense precipitates, nanosized colloids and liquid coacervates. In the past 50 years, much progress has been achieved to understand the principles behind the phase separation induced by the interaction of two oppositely charged polyelectrolytes in aqueous solutions, especially for symmetric systems (systems in which both polyions have similar molecular weight and concentration). However, in recent years, the complexation of polyelectrolytes with alternative building blocks such as small charged molecules (multivalent inorganic species, oligopeptides, and oligoamines, among others) has gained attention in different areas. In this review, we discuss the physicochemical characteristics of the complexes formed by polyelectrolytes and multivalent small molecules, putting a special emphasis on their similarities with the well-known polycation-polyanion complexes. In addition, we analyze the potential of these complexes to act as versatile functional platforms in various technological fields, such as biomedicine and advanced materials engineering.
RESUMO
Nanotechnology plays a crucial role in vaccine development and provides the opportunity to design functional nanoparticles (Np) of different compositions, sizes, charges and surface properties for biomedical applications. The present study aims to evaluate a complex coacervate-like Np composed of poly(allylamine hydrochloride) (PAH) and tripolyphosphate (Tpp) as a safe vehicle and adjuvant for systemic vaccines. We investigated the activation of different antigen-presenting cells (APCs) with Np-PAH and its adjuvanticity in Balbc/c and different KO mice that were intraperitoneally immunized with Np-OVA. We found that Np-PAH increased the expression of CD86 and MHCII and promoted the production and secretion of interleukin-1ß (IL-1ß) and IL-18 through the inflammasome NLRP3 when macrophages and dendritic cells were co-incubated with LPS and Np-PAH. We evidenced an unconventional IL-1ß release through the autophagosome pathway. The inhibition of autophagy with 3-methyladenine reduced the LPS/Np-PAH-induced IL-1ß secretion. Additionally, our findings showed that the systemic administration of mice with Np-OVA triggered a significant induction of serum OVA-specific IgG and IgG2a, an increased secretion of IFN-γ by spleen cells, and high frequencies of LT CD4 + IFN-γ + and LT CD8 + IFN-γ + . In conclusion, our findings show that PAH-based Np promoted the inflammasome activation of innate cells with Th1-dependent adjuvant properties, making them valuable for formulating of novel preventive or therapeutic vaccines for infectious and non-infectious diseases.
RESUMO
This work reports the phase behavior and electrochemical properties of liquid coacervates made of ferricyanide and poly(ethylenimine). In contrast to the typical polyanion/polycation pairs used in liquid coacervates, the ferricyanide/poly(ethylenimine) system is highly asymmetric because poly(ethylenimine) has approximately 170 charges per molecule, while ferricyanide has only 3. Two types of phase diagrams were measured and fitted with a theoretical model. In the first type of diagram, the stability of the coacervate was studied in the plane given by the concentration of poly(ethylenimine) versus the concentration of ferricyanide for a fixed concentration of added monovalent salt (NaCl). The second type of diagram involved the plane given by the concentration of poly(ethylenimine) vs the concentration of the added monovalent salt for a fixed poly(ethyleneimine)/ferricyanide ratio. Interestingly, these phase diagrams displayed qualitative similarities to those of symmetric polyanion/polycation systems, suggesting that coacervates formed by a polyelectrolyte and a small multivalent ion can be treated as a specific case of polyelectrolyte coacervate. The characterization of the electrochemical properties of the coacervate revealed that the addition of monovalent salt greatly enhances charge transport, presumably by breaking ion pairs between ferricyanide and poly(ethylenimine). This finding highlights the significant influence of added salt on the transport properties of coacervates. This study provides the first comprehensive characterization of the phase behavior and transport properties of asymmetric coacervates and places these results within the broader context of the better-known symmetric polyelectrolyte coacervates.
RESUMO
Designing effective drug nanocarriers that are easy to synthesize, robust, and nontoxic is a significant challenge in nanomedicine. Polyamine-multivalent molecule nanocomplexes are promising drug carriers due to their simple and all-aqueous manufacturing process. However, these systems can present issues of colloidal instability over time and cellular toxicity due to the cationic polymer. In this study, we finely modulate the formation parameters of poly(allylamine-tripolyphosphate) complexes to jointly optimize the robustness and safety. Polyallylamine was ionically assembled with tripolyphosphate anions to form liquid-like nanocomplexes with a size of around 200 nm and a zeta potential of -30 mV. We found that nanocomplexes exhibit tremendous long-term stability (9 months of storage) in colloidal dispersion and that they are suitable as protein-loading agents. Moreover, the formation of nanocomplexes induced by tripolyphosphate anions produces a switch-off in the toxicity of the system by altering the overall charge from positive to negative. In addition, we demonstrate that nanocomplexes can be internalized by bone-marrow-derived macrophage cells. Altogether, these nanocomplexes have attractive and promising properties as delivery nanoplatforms for potential therapies based on the immune system activation.