PEGylated Albumin-Based Drug Carriers for the Treatment of Experimental Stroke

Stroke is the leading cause of mortality and disability worldwide. The goal of this study was to design stable, small-sized polyethylene glycol (PEG)/albumin nanoparticles (NPs) for delivering drugs targeting various phases of stroke recovery.

RP-HPLC (Reversed-Phase High-Performance Liquid Chromatography) and spectrophotometry were used to assess the stability and effectiveness of the drug carriers. The dynamic light scattering (DLS) technique was employed to evaluate the size and zeta potential of the particles. The integrity of the blood–brain barrier (BBB) in laboratory rats was assessed by measuring Evans Blue (EB) leakage after intracranial injection of 3% H₂O₂. AutoDock Tools 1.5.7 was used to analyze the compatibility of the polymers with albumin.

The particles exhibited high drug-loading efficiency. In all groups, the most prevalent particle size averaged 211.09 ± 92.72 nm. The drug-loaded particles exhibited prolonged circulation and had a half-life (T₁/₂) ranging from 7.64 to 13 days. Furthermore, both albumin particles and PEGylated albumin carriers loaded with dexamethasone and allopurinol significantly preserved blood–brain barrier (BBB) integrity (2.92 ± 0.4 µg, p < 0.04), as indicated by reduced Evans Blue (EB) extravasation (6.73 ± 0.58 µg) compared to the control group (9.12 ± 1.2 µg, p < 0.04, t-test).

The protective effect of albumin carriers on the BBB may be attributed to an increase in blood oncotic pressure, which helps limit edema formation. PEG/albumin drug-loaded carriers demonstrated greater stability, as indicated by their zeta potential, and exhibited a more pronounced BBB-preserving effect due to the combined actions of albumin and the loaded drugs.

In this study, stable, layered NPs carrying different drugs were synthesized that could be applied for the treatment of experimental stroke.