Nanoformulation of fibrinogen by thermal stabilization of its electrostatic complexes with hyaluronic acid

The formulation of well-defined and stable fibrinogen-based nanoparticles (NPs) without the use of any chemical reaction or any toxic organic solvent is reported. Electrostatic interaction between hyaluronic acid (HA) and fibrinogen (Fbg) leads to well-defined complexes at acidic pH which however readily dissolve at neutral pH. On the other hand, when thermal treatment is applied on the pre-formed complexes NPs keep their integrity. Circular dichroism indicates that the protein's native secondary conformation in the final NPs is not affected by the formulation. The tendency of the complexes to aggregate at elevated ionic strengths is greatly suppressed after the application of the temperature treatment protocol. This characteristic is even more pronounced at neutral pH and it is connected to the enhanced surface charge of the NPs. The encapsulation of the hydrophobic compound curcumin causes only weak secondary aggregation. This work shows that the ability of Fbg to self-assemble upon thermal treatment can be effectively used to stabilize Fbg nanoformulations inside complexes with polysaccharides.