Innovative Nanoformulations: Overcoming Chemotherapy Resistance

Paclitaxel–pterostilbene nanoparticles markedly increase paclitaxel solubility and antitumor activity, offering a direct translational route to overcome taxane resistance by enabling higher intratumoral delivery with less reliance on solvent excipients.

Current paclitaxel formulations are constrained by poor water solubility and solvent-dependent toxicity, producing variable exposure. Nanoformulation through co‑assembly or co‑encapsulation aims to replace solvent vehicles, improving solubility, tumor accumulation, and the therapeutic index—changes that directly address mechanisms of resistance by raising intratumoral drug levels.

In vitro characterization in A549 and A549/T cell lines showed a sevenfold increase in paclitaxel water solubility, quantified by solubility testing and HPLC/LC‑MS. The improvement is attributed to amorphous co‑assembly, better drug dispersion, and enhanced cellular uptake that together support greater bioavailable dose delivery. Solubility gains translated into higher in vitro exposure and measurable cytotoxicity in A549 models.

The nanoparticles also reduced expression of drug‑resistance proteins—most notably P‑glycoprotein and CDK1—which correlated with increased intracellular paclitaxel concentrations and greater tumor‑cell kill in A549 and A549/T models .

Likely clinical advantages include higher effective intratumoral dosing without raising systemic exposure, lower solvent‑related toxicity risk, and applicability to taxane‑resistant tumors.

Key takeaways:

• Co‑assembly of paclitaxel with pterostilbene yields a sevenfold solubility increase and improved cytotoxicity against taxane‑resistant lung cancer cells.
• Patients with taxane‑resistant tumors—who may benefit from greater intratumoral delivery and reduced solvent toxicity—are the primary group likely to gain clinical benefit.
• Priorities are PK and safety profiling, establishing scalable GMP manufacturing, and launching early‑phase trials enrolling resistant‑disease cohorts.