Phytosomal Based Delivery of Ellagic Acid: Formulation of an Oral Reconstitutable Suspension and Anthelmintic Evaluation

Background: Helminthic infections constitute a serious global health burden. Even though ellagic acid exhibits remarkable anthelmintic activity, its poor aqueous solubility and low oral bioavailability impede its widespread clinical utility.

Aim: To formulate and characterize an ellagic acid phytosomal dry powder for oral suspension (DPOS) and evaluate its anthelmintic efficacy through in vitro and in silico approaches.

Methodology: Ellagic acid phytosomes were prepared with soya lecithin via solvent evaporation and homogenized to formulate a DPOS matrix. Entrapment efficiency was quantified using UV-Vis spectrophotometry, and complexation was confirmed by FTIR spectroscopy. Surface morphology of isolated phytosomes was characterized by scanning electron microscopy (SEM). Following reconstitution, optical microscopy was employed for particle size determination alongside assessments of sedimentation volume, pH, viscosity, and redispersibility. Anthelmintic efficacy was evaluated against Pheretima posthuma with albendazole as a reference drug. In silico SwissADME screening assessed physicochemical properties and drug-likeness, while molecular docking against the helminth tubulin receptor (PDB: 1SA0) determined binding affinities.

Results: Scanning electron microscopy of isolated phytosomes revealed discrete micro-particulates ranging from 1.24 to 9.98 µm, with an entrapment efficiency of 85.24%. Upon reconstitution, the DPOS demonstrated a mean particle size of 11.15 µm, rapid redispersibility, and high physical stability (F = 0.92 +/- 0.02). Although conventional in vitro dissolution was unfeasible due to infrastructural limitations, enhanced wetting, dispersibility, and bio-uptake of the phospholipid matrix were corroborated biologically: the 100 mg/mL phytosomal suspension induced earthworm paralysis (34.00 +/- 2.18 min) and death (59.25 +/- 4.91 min) comparable to albendazole (33.28 +/- 1.17 min) and (57.90 +/- 4.31 min, respectively). In silico profiling confirmed the favorable drug-likeness of ellagic acid, and molecular docking demonstrated superior binding affinity to tubulin (-8.654 kcal/mol) relative to albendazole (-6.526 kcal/mol).