Paclitaxel (PTX) is a gold standard chemotherapeutic agent for breast, ovarian, pancreatic and
non-small cell lung carcinoma. However, in clinical use PTX can have adverse side effects or inadequate pharmacodynamic parameters, limiting its use. Nanotechnology is often employed to reduce the therapeutic dosage required for effective
therapy, while also minimizing the systemic side effects of
chemotherapy drugs. However, there is no nanoformulation of
paclitaxel with chemosensitization motifs built in. With this objective, we screened eleven
pharmaceutical excipients to develop an alternative
paclitaxel nanoformulation using a self-assembly method. Based on the screening results, we observed
tannic acid possesses unique properties to produce a
paclitaxel nanoparticle formulation, i.e.,
tannic acid-
paclitaxel nanoparticles. This stable TAP nanoformulation, referred to as TAP nanoparticles (TAP NPs), showed a spherical shape of ~ 102 nm and negative zeta potential of ~ -8.85. The presence of PTX in TAP NPs was confirmed by Fourier Transform Infrared (FTIR) spectra, thermogravimetric analyzer (TGA), and X-ray diffraction (XRD). Encapsulation efficiency of PTX in TAP NPs was determined to be ≥96%. Intracellular
drug uptake of plain
drug PTX on
breast cancer cells (MDA-MB-231) shows more or less constant
drug levels in 2 to 6 h, suggesting
drug efflux by the P-gp transporters, over TAP NPs, in which PTX uptake was more than 95.52 ± 11.01% in 6 h, as analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Various
biological assays such as proliferation, clonogenic formation, invasion, and migration confirm superior anticancer effects of TAP NPs over plain PTX at all tested concentrations. P-gp expression,
beta-tubulin stabilization, Western blot, and microarray analysis further confirm the improved therapeutic potential of TAP NPs. These results suggest that the TAP nanoformulation provides an important reference for developing a therapeutic nanoformulation affording pronounced, enhanced effects in
breast cancer therapy.