Poly(allylamine)-tripolyphosphate Ionic Assemblies as Nanocarriers: Friend or Foe?

Abstract

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 liquidlike 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.

Poly(allylamine)/tripolyphosphate nanocomplex coacervate as a NLRP3-dependent systemic adjuvant for vaccine development

“…The positively charged PAH was mixed with the negatively charged crosslinker Tpp at a ratio R=[Tpp]/[PAH]=0.6 (Figure 1A). The physicochemical properties of the self-assembled spherical nanoparticles, with a diameter of 200 nm and a negative charge potential of -23 mV, were measured using transmission electron microscopy (TEM) (Figure 1B) and dynamic light scattering (DLS) (Figure 1C) 16 . To study the interaction of PAH/Tpp Nps with cells, we exposed the murine J774 macrophages to Np.…”

“…PAH/Tpp nanoparticles were prepared by following the procedure described in Apuzzo et al 16 . Briefly, 0.125 V f ml of PAH (17.5 kDa, Sigma-Aldrich, St. Louis, MO, USA) 40mM (monomer concentration) at pH 8.5, 0.75 V f ml of deionized water, and 0.125 V f ml of Tpp (Sigma-Aldrich, St. Louis, MO, USA) 24mM at pH 8.5 were mixed under constant stirring at room temperature (RT).…”

“…By this, Tpp is one of the most used crosslinkers for synthesizing soft nanoparticles with biomedical applications 15 . As we recently demonstrated, the mixture of PAH and Tpp in an aqueous solution gives rise to the formation of a highly stable colloidal dispersion of complex coacervates, characterized by size and surface charge that enable the loading of proteins with different molecular weights and charges 16 .…”

“…The production of cytokines and chemokines, along with the expression of CD80, CD86, and MHCII on the cell surface, transforms these cells into APCs with an increased ability to activate T lymphocytes 36–38 . We previously found that the positive PAH-based nanoparticles are non-toxic and are internalized by phagocytic cells with intracellular localization in early and late endosomes 16 . In this study, we found that dendritic cells and macrophages undergo activation upon nanoparticle uptake, cell migration, and promotion of Th1-dependent adaptive immunity.…”

Utilization of CO2-captured poly(allylamine) as a polymer surfactant for nanoarchitecture production in a closed CO2 cycle

“…65 Additionally, the commercial availability and easy modifiability of PAA allow for broad design and conversion into unique materials, 66 including not only CO 2 absorbents 67,68 but also polymer surfactants 69 and biocompatible polymers for medical use. 70 Material design aimed at replacing existing functional materials with PAA that has stored CO 2 , facilitates industrial utilization of CO 2 -captured absorbents. Utilizing CO 2 stores is environmentally significant because allowing them to increase without utilization could cause additional pollution from the CO 2 stores, further contributing to global environmental degradation.…”