Increased blood-brain barrier permeability of neuroprotective drug by colloidal serum albumin carriers.

Encapsulation possibilities of two neuroprotective drugs of slightly different structures, kynurenic acid (KYNA) and its more hydrophilic analogue (SzR72), are studied in bovine serum albumin (BSA) nanoparticles (NPs) to increase their permeability through the blood-brain barrier (BBB). The effect of various preparation conditions such as protein concentration, protein-to-drug ratio, pH, ionic strength, type, and amount of desolvation agent and cross-linker concentration are discussed. It was found that the encapsulation proved to be successful only if the drugs are added to the pre-prepared BSA NPs. If the pH of the medium is adjusted to 4.0 instead of 7.4 the drug loading increased (from 4.5 % to 20.7 % for KYNA) due to the electrostatic interaction between the oppositely charged functional groups accompanied by significant secondary structural changes verified by circular dichroism spectroscopy (CD) suggesting the drug insertion in the hydrophobic pockets of BSA. The in vitro polar brain lipid extract (porcine) based permeability test proved the aimed three-, or fourfold higher BBB specific penetration for KYNA in the carrier relative to the unformatted drug.

Serum protein-hyaluronic acid complex nanocarriers: Structural characterisation and encapsulation possibilities.

A protein-polysaccharide-based potential nanocarrier system have been developed via a simple, one-step preparation protocol without the use of long-term heating and the utilization of hardly removable crosslinking agents, surfactants, and toxic organic solvents. To the best of our knowledge, this article is the first which summarizes in detail the pH-dependent quantitative relationship between the bovine serum albumin (BSA) and hyaluronic acid (HyA) confirmed by several physico-chemical techniques. The formation of colloidal complex nanoconjugates with average diameter of ca. 210-240 nm is strongly depend on the pH and the applied BSA:HyA mass ratio. Particle charge titrations studies strongly support the core-shell type structure, where the BSA core is covered by a thick HyA shell. Besides the optimization of these conditions, the drug encapsulation capacity and the dissolution profiles have been also studied for ibuprofen (IBU) and 2-picolinic acid (2-PA) as model drugs.