Formulation and Evaluation of Nanoparticle-Based Drug Delivery Systems for Targeted Cancer Therapy
Keywords:
Nanoparticles, PLGA, targeted drug delivery, cancer therapy, nanoprecipitation, factorial design, drug release kinetics, entrapment efficiency, cytotoxicity, EPR effectAbstract
Traditional chemotherapy faces challenges such as the low water solubility of numerous anticancer drugs, non-specific distribution within the body, quick elimination from the system, and toxicity that limits the dosage due to harm to healthy tissues. Nanoparticle-based drug delivery systems (NDDS) have been developed as a promising approach to address these issues by allowing for controlled drug release, enhanced pharmacokinetics, and selective accumulation in tumors through passive (enhanced permeability and retention, EPR) and active (ligand-mediated) targeting methods. This study involved the formulation of poly(lactic-co-glycolic acid) (PLGA) nanoparticles containing a model anticancer drug (doxorubicin hydrochloride) using the nanoprecipitation (solvent displacement) method. The process was optimized with a 3² factorial design, considering polymer and surfactant concentrations as independent variables. Nine different formulations (F1–F9) were created and assessed for particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (EE), drug loading (DL), surface morphology, in vitro drug release, release kinetics, and short-term stability. The optimized formulation (F5) showed a mean particle size of 148.6 ± 3.2 nm, a PDI of 0.181 ± 0.02, a zeta potential of −24.3 ± 1.1 mV, an entrapment efficiency of 78.4 ± 2.6%, and a drug loading of 8.9 ± 0.4%. Transmission electron microscopy revealed spherical, distinct particles with smooth surfaces. In vitro release experiments in phosphate-buffered saline (pH 7.4, 37 °C) exhibited a biphasic release pattern, with an initial burst (~12% within 2 hours) followed by a sustained release over 96 hours, which aligned best with the Korsmeyer–Peppas model (R² = 0.988, n = 0.41), suggesting Fickian diffusion along with polymer erosion. Cytotoxicity tests (MTT) on MCF-7 breast cancer cells showed that the nanoparticle formulation had significantly improved anticancer activity (IC₅₀ = 6.2 ± 0.5 µg/mL) compared to the free drug solution (IC₅₀ = 18.4 ± 1.2 µg/mL, p < 0.001), while blank nanoparticles exhibited minimal cytotoxicity, indicating the carrier's biocompatibility. Stability studies conducted under accelerated and refrigerated conditions over 90 days demonstrated that storage at 4 ± 2 °C maintained particle size, PDI, and entrapment efficiency much better than storage at 25 ± 2 °C/60% RH. These results suggest that PLGA nanoparticles are a viable, biocompatible platform for the targeted delivery of anticancer drugs, meriting further in vivo pharmacokinetic and tumor-targeting studies.
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