Development and Evaluation of Icariin-Loaded PLGA-PEG Nanoparticles for Potentiation the Proapoptotic Activity in Pancreatic Cancer Cells

Therapeutic efficacy of antineoplastic agents possessing a selective target to the nucleus of the cancer cells could be enhanced through novel formulation approaches. Thus, towards improvement of anticancer potential of icariin (ICA) on pancreatic cancer, the drug was entrapped into the polymeric poly lactic-co-glycolic acid (PLGA) with polyethylene glycol (PEG) as diblock copolymer. Optimization of the formulation was done using Statgraphics software to standardize percentages of PEG-PLGA and tween 80 (TW80) to obtain the smallest particle size. The optimized formulation was found to be in nanometer size and low PDI (0.321). Optimized formula enhanced cytotoxicity and apoptotic potential, compared with ICA-raw, against pancreatic cancer cell lines (aspc-1). The entrapment efficiency of the polymeric micelles was 72.34 +/- 2.3% with 93.1 +/- 6.5% release of ICA within 72 h. There was a twofold increase in apoptosis and sevenfold increase in necrosis of aspc-1 cells when incubated with raw ICA compared to control cells. Further, loss of mitochondrial membrane potential (similar to 50-fold) by the ICA-loaded PMs and free drug compared to control cells was found to be due to the generation of ROS. Findings of cell cycle analysis revealed the significant arrest of G2-M phase of aspc-1 cells when incubated with the optimized formulation. Simultaneously, a significantly increased number of cells in pre-G1 revealed maximum apoptotic potential of the drug when delivered via micellar formulation. Finally, upregulation of caspase-3 established the superiority of the PMs approach against pancreatic cancer. In summary, the acquired results highlighted the potentiality of PMs delivery tool for controlling the growth of pancreatic cancer cells for improved efficacy.

Automated summary

The therapeutic efficacy of antineoplastic agents that target the nucleus of cancer cells can be enhanced through novel formulation approaches. The encapsulation of icariin in PLGA with PEG as a diblock copolymer significantly increased its cytotoxicity and apoptotic potential against pancreatic cancer cells. The polymeric micelles demonstrated high entrapment efficiency and release rate, suggesting the potential of PMs delivery tool in controlling the growth of pancreatic cancer cells for improved efficacy.