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. [Display omitted] •Encapsulation of neuroprotective compounds to serum albumin particles was carried out.•Drug loading can be greatly controlled by drug/protein ratio and pH of the carrier.•Under 20 % of kynurenic acid (KYNA) drug loading 180 nm sized particles were formed.•Protein carrier results three-or fourfold blood brain barrier penetration for KYNA.