Effective applicability of serum albumin-hyaluronic acid (HyA) conjugates as potential drug delivery colloidal particles having d ∼ 220 – 260 nm average size has been presented for encapsulation of ibuprofen (IBU). Increased IBU content with drug loading of 30 % can be achieved via combination of the serum albumin proteins with biodegradable HyA polysaccharide. After optimization of the synthesis protocols and the characterization of the prepared systems for both bovine (BSA) and human serum albumin (HSA)-based particles, in vitro dissolution and intestinal-specific permeability studies were also performed. It was established that these protein/polysaccharide colloidal carriers have more favourable dissolution, intestinal permeability, and flux features than the unformulated IBU which is greatly controlled by the net charge of serum albumins at pH = 6.50. The nanosized carrier formula, which provides enhanced solubility, accelerated dissolution, and greater permeability, may represent a more controlled, lower dose loading, and gastric mucosa-sparing therapeutic solution in the high-dose IBU therapy.