Development and Characterization of PLGA-Based Doxorubicin Nanoparticles for Enhanced and Targeted Therapeutic Delivery

Original Article

Abstract

Objectives: To develop and characterize doxorubicin-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles, and to compare their physicochemical properties, drug loading, release behavior, computational drug–target compatibility, cellular uptake, and in vitro therapeutic performance with those of the free drug.

Methods: Nanoparticles were prepared by emulsion–solvent evaporation and optimized across five batches (F1–F5), using particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency (EE), drug loading (DL), and 24-h release as critical quality attributes. The optimized batch was characterized by dynamic light scattering, electrophoretic light scattering, FT-IR, XRD, and SEM/TEM. Release was studied by dialysis and fitted to zero-order, first-order, Higuchi, and Korsmeyer–Peppas models. Molecular docking, cellular uptake, target-cell inhibition, and normal-cell cytotoxicity were then assessed (n = 3).

Results: The optimized formulation (F4) had a hydrodynamic diameter of 158.7 ± 3.9 nm, a PDI of 0.206 ± 0.011, a zeta potential of −28.9 ± 1.3 mV, an EE of 92.6 ± 1.4%, and a DL of 13.4 ± 0.6%. Release was sustained, reaching 71.2 ± 1.8% at 24 h compared with 99.1 ± 0.7% for the free drug, and was best described by the Korsmeyer–Peppas model (n = 0.556; R² = 0.995), indicating mixed diffusion- and erosion-controlled transport. Cellular uptake increased by 57.0% (p < 0.001). At 5 µg/mL, target-cell inhibition rose from 60.0% to 79.2% (p < 0.001), while normal-cell toxicity fell from 30.0% to 21.6% (a 28.0% reduction; p < 0.01). The target-cell IC50 decreased from 3.6 to 2.0 µg/mL, a 1.8-fold gain in apparent potency.

Conclusion: The PLGA–doxorubicin nanoparticles combined uniform nanoscale size, high drug incorporation, sustained release, enhanced cellular uptake, and an improved balance of efficacy and selectivity in vitro. These findings support the formulation as a proof-of-concept platform for preclinical development. Active receptor-specific targeting and in vivo benefit remain to be demonstrated.