Improving Paclitaxel permeation and anticancer efficacy through Soluplus-based solid dispersion with Piperine

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Cancer Therapeutics

Background:

• Paclitaxel (PTX) exhibits poor aqueous solubility and toxicity issues with conventional formulations.
• Piperine (PPN) acts as a bioenhancer and P-glycoprotein inhibitor, potentially improving PTX efficacy.
• Metastatic breast cancer requires improved therapeutic strategies due to drug limitations.

Purpose of the Study:

• To develop and optimize a Soluplus-based Paclitaxel-Piperine (PTX-PPN) solid dispersion.
• To enhance PTX solubility, intestinal permeation, and anticancer activity.
• To evaluate the formulation's potential in treating metastatic breast cancer cells.

Main Methods:

• Solid dispersions prepared using freeze-drying with varying PTX-PPN-Soluplus ratios.
• Formulations characterized for drug content, solubility, dissolution, and solid-state properties (FTIR, DSC, XRD, microscopy).
• Ex vivo intestinal permeation, in vitro cytotoxicity, and apoptosis assays conducted in 4T1 metastatic breast cancer cells.

Main Results:

• Optimized PTX-PPN-Soluplus (1:1:1.5) formulation significantly increased solubility of both PTX and PPN.
• Solid-state analysis confirmed the amorphous conversion of PTX and PPN.
• Enhanced PTX intestinal permeation (6-fold increase in flux) and superior cytotoxicity (1.6-fold reduction in cell viability) observed.
• The formulation induced significantly higher apoptosis compared to PTX-PPN alone.

Conclusions:

• The developed PTX-PPN-Soluplus solid dispersion effectively overcomes PTX solubility challenges.
• This system demonstrates potential for improved anticancer efficacy in metastatic breast cancer.
• The formulation offers a promising strategy for broader clinical application of PTX.