Vol. 2, Issue 1, Part A (2025)

Background: Poor aqueous solubility remains one of the most significant challenges in the formulation and delivery of modern therapeutic agents, with nearly 40% of commercially marketed drugs exhibiting limited dissolution and inconsistent bioavailability. Nanoparticle-based delivery systems have emerged as an advanced strategy to enhance the solubility, dissolution rate, and systemic absorption of such drugs.

Objective: This study aimed to develop and experimentally validate a nanoparticle-based delivery system to enhance the bioavailability of ondansetron hydrochloride, a model poorly water-soluble drug, by employing biodegradable PLGA polymer through solvent evaporation and to compare its performance with conventional formulations.

Methods: Ondansetron-loaded PLGA nanoparticles were prepared using a single-emulsion solvent evaporation method and characterized for particle size, zeta potential, polydispersity index, drug loading, and entrapment efficiency. In vitro drug release was evaluated using the dialysis method in phosphate buffer saline (pH 7.4), and in vivo bioavailability was assessed in male Wistar rats following oral administration of both nanoparticle formulation and conventional solution. Data were statistically analyzed using ANOVA and Student’s t-test.

Results: The optimized nanoparticles exhibited a mean particle size of 178±9 nm, a PDI < 0.25, and a zeta potential of −23 mV, indicating good stability and uniform dispersion. The formulation achieved an entrapment efficiency of 85% and demonstrated a biphasic release profile with a sustained release over 24 hours, following Korsmeyer-Peppas kinetics (R² = 0.983). In vivo pharmacokinetic analysis revealed a 2.1-fold enhancement in bioavailability, with significantly higher Cₘₐₓ and AUC₀-∞ values compared to the conventional solution (p<0.001). A moderate correlation (r = 0.74) between in vitro release and in vivo AUC indicated predictive translational potential.

Conclusion: The study confirmed that PLGA-based nanoparticles effectively improve the solubility, dissolution, and bioavailability of poorly water-soluble drugs. The findings highlight nanoparticles as a promising platform for oral drug delivery, offering extended therapeutic effect, reduced dosing frequency, and improved patient compliance. Further optimization and scale-up can facilitate translation into clinically viable and industrially reproducible formulations for a broad range of hydrophobic drugs.