Development and Optimisation of Docetaxel-Loaded Polymeric Nanoparticles for Oral Chemotherapy in Breast Cancer

Abstract

Docetaxel (DTX)-loaded polymeric nanoparticles composed of Eudragit RL and RS 100 were developed by solvent evaporation using D-α-tocopheryl polyethene glycol 1000 succinate as an emulsifier and optimised by Central Composite Design. The effects of homogenisation and sonication times on entrapment efficiency (%EE) and drug release (%DR) were statistically analysed across nine batches. Particle size (PS) ranged from 302 ± 1.0 to 502 ± 2.0 nm, and zeta potential (ZP) from 25.8 ± 2.5 to 42.9 ± 1.7 mV. %EE and %DR (pH 1.2 for 2 h, then pH 7.4 for 22 h, 40 mL medium at 37 ± 0.5 °C) ranged from 69.32 ± 3.77 to 92.71 ± 0.16% and 19.24 ± 3.03 to 49.17 ± 1.98%, respectively. Optimised DTX nanoparticles (DNPs) showed EE of 78.18 ± 0.56%, DR of 46.21 ± 1.41% at 24 h, PS of 357.9 ± 2.4 nm, and ZP of 42.9 ± 3.7 mV. Scanning electron microscopy revealed ~300 nm cuboidal particles with smooth surfaces. X-Ray Diffraction and Differential Scanning Colorimetry confirmed reduced drug crystallinity in DNPs. In vitro haemolysis assays showed ~11.5-fold lower haemolytic potential (p < 0.0001) versus DTX, confirming improved safety. Fluorescence microscopy indicated enhanced cellular uptake of DNPs in MDA-MB-231 cells, while cytotoxicity assays of DNPs showed a lower IC50 (39.52 µM) compared to DTX (60.81 µM), demonstrating superior anticancer efficacy. Overall, DNPs represent a promising oral chemotherapy platform for breast cancer management.