Enhancing Etoposide Aqueous Solubility and Anticancer Activity with L-Arginine.

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery
• Cancer Therapeutics

Background:

• Etoposide (VP-16) is a crucial chemotherapy drug with poor water solubility.
• Improving VP-16 solubility can enhance its therapeutic efficacy and administration.
• L-arginine (ARG) is explored as a potential solubilizing agent for hydrophobic drugs.

Purpose of the Study:

• To investigate the potential of L-arginine (ARG) to improve etoposide (VP-16) water solubility.
• To evaluate the impact of ARG on VP-16's anticancer activity and cellular uptake.
• To determine optimal conditions for a freeze-dried VP-16:ARG formulation.

Main Methods:

• Factorial design for optimizing drug solubility after freeze-drying.
• Physicochemical characterization using XRD, SEM, NMR, and FTIR.
• Mass spectrometry for drug stability analysis.
• LC-MS/MS for cellular uptake and cell viability assays on MCF-7 cells.

Main Results:

• A VP-16:ARG ratio of 4:10 (w/w) increased VP-16 apparent solubility by ~65-fold and dissolution rate by 3.5-fold.
• The VP-16-ARG interaction converted the drug from crystalline to amorphous state.
• Anticancer activity was reduced at lower concentrations due to decreased uptake but enhanced at higher concentrations via synergistic effects.

Conclusions:

• L-arginine effectively improves etoposide solubility and dissolution, forming an amorphous complex.
• The VP-16-ARG complex exhibits concentration-dependent anticancer activity, with synergistic effects at higher concentrations.
• Optimized ARG concentrations may offer benefits for etoposide-based chemotherapy.