Formulation and Evaluation of Hecogenin-Loaded Phycocyanin Nanosponges for Treatment of Parkinson’s Disease

Parkinsonian disease (PD) is a progressive neurodegenerative disease that needs long-term drug delivery treatment beyond
the blood-brain barrier. The objectives of the present study were to synthesize and optimize Phycocyanin nanosponges
loaded with Hecogenin into optimality by using biocompatible polymers (PVA /PVP) to improve brain-based drug delivery.
The nanosponges were prepared through solvent diffusion, and its optimization process was based upon a Box-Behnken
Design. The optimized Run 4 exhibited a protein size (193 nm), zeta potential of the prepared entrapping capsule (-32.2
mV), PDI of 0.12, excellent entrapment efficiency (88.5 percent), and a prolonged release drug (80.5 percent in 24-hour
period). FTIR analysis confirmed drug-polymer compatibility, while DSC and XRD analyses revealed the amorphous
transformation of Hecogenin, improving solubility and stability. Molecular docking studies showed strong binding
affinities of Hecogenin to Parkinson’s-related targets MAO-B and Alpha-Synuclein, with favorable MolDock scores
(~−166.93) and confirmed BBB permeability. These findings indicate that Hecogenin-loaded Phycocyanin nanosponges
are a promising brain-targeted delivery platform for effective PD management through improved bioavailability and
sustained release.