FORMULATION AND PHYSICOCHEMICAL CHARACTERIZATION OF PACLITAXEL-LOADED PLGA NANOPARTICLES WITH ENHANCED SOLUBILITY AND IN VITRO ANTICANCER ACTIVITY
Objective: Paclitaxel is a widely used chemotherapeutic agent with extremely poor aqueous solubility (~0.3 µg/ml), which significantly limits its bioavailability and therapeutic efficacy. The present study aimed to develop and characterize paclitaxel-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles to enhance solubility, dissolution behavior, and in vitro anticancer activity. Methods: Nanoparticles were prepared using the solvent evaporation method and optimized by varying the drug-to-polymer ratio and homogenization conditions. The optimized formulation was characterized for particle size, polydispersity index (PDI), and zeta potential. Differential scanning calorimetry (DSC) and x-ray diffraction (XRD) were used to evaluate the physical state of paclitaxel, while Fourier-transform infrared spectroscopy (FTIR) analysis was performed to assess chemical compatibility between the drug and polymer. Solubility and dissolution studies were conducted, and cytotoxicity was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results: The optimized formulation exhibited an average particle size of 195±5 nm, polydispersity index of 0.11, and zeta potential of −32±2 mV, indicating good colloidal stability. DSC and XRD analysis confirmed the transformation of paclitaxel from crystalline to amorphous form within the polymer matrix. FTIR analysis demonstrated chemical compatibility between the drug and polymer. The nanoparticle formulation significantly enhanced aqueous solubility, achieving approximately a 24-fold increase (from 0.3 µg/ml to 7.2 µg/ml). In vitro dissolution studies revealed sustained drug release with more than 85% release within 24 h, whereas the native drug showed less than 20% release. Cytotoxicity evaluation using the MTT assay demonstrated improved anticancer activity, with reduced IC₅₀ values compared to the native drug. Conclusion: These findings demonstrate that PLGA-based nanoparticles represent a promising approach for improving the solubility and therapeutic performance of poorly water-soluble anticancer agents.