Intravenous paclitaxel delivered by a vitamin E nanocarrier as a safe and economical alternative to albumin-bound nanoparticles.

BACKGROUND: Paclitaxel is a widely used chemotherapeutic agent for solid tumors; however, its clinical application is limited by extremely low aqueous solubility and the use of toxic excipients in conventional formulations. Albumin-bound paclitaxel nanoparticles improve solubility but remain costly and present challenges related to stability and manufacturing. This study aimed to develop a synthetic and economical TPGS-based solubilization system as an alternative to intravenous paclitaxel formulations with enhanced anticancer efficacy. METHODS: A series of D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) micelles and TPGS–cosolvent systems were prepared and evaluated for solubilization efficiency, particle size, and homogeneity. The promising formulation (F3) was examined for in vitro cytotoxicity in MCF-7, MDA-MB-231, HeLa, and HCT116 cell lines. Mechanistic studies, including cell-cycle analysis, Annexin V/PI apoptosis staining, assessment of mitochondrial membrane potential (MMP), and DAPI nuclear imaging, were conducted to characterize the anticancer activity in MCF-7 cells. RESULTS: F3 markedly improved paclitaxel solubility and formed nanosized homogenous micellar dispersions suitable for intravenous delivery. Across all cell lines, F3 demonstrated significantly enhanced cytotoxicity, producing 4–7-fold lower IC₅₀ values compared with free paclitaxel and albumin-bound paclitaxel (Taxonab®). In MCF-7 cells, F3 induced prominent G₂/M arrest, the highest Sub-G1 apoptotic population, and pronounced mitochondrial depolarization, consistent with mitochondria-mediated apoptosis. DAPI staining confirmed nuclear fragmentation and reduced cell density. CONCLUSION: The TPGS-based paclitaxel formulation significantly enhances drug solubility, cellular uptake, and apoptotic activity, outperforming both free paclitaxel and albumin-bound nanoparticles. This synthetic, scalable, and cost-effective platform represents a promising alternative for intravenous paclitaxel delivery and warrants further preclinical evaluation.