Table 5.

Summary of the results for various piperine (Pip) delivery methods.

Piperine Delivery Method	Structure	Solubility and Release Kinetics	Targeting Specifications
Pip (free form)		Higher solubility in PBS at acidic pH 5 than 6.8, 7.4, and 9.	Moderate cytotoxicity towards normal WI-38 cells. Weak activity against HCT116 colon cancer cells (monolayer and spheroids). Not effective. Non-targeting for colon.
HAP-Pip or HAP-P-Pip—Pip-loaded HAP not modified or modified with phosphonate. Loading at pH 7.2 and 9.3		Short-term release. Release 100% of Pip capacity ~36 h (pH 6.8) and 24 h (pH 5).	Moderate cytotoxicity towards normal cells. High anticancer effect on monolayer colon cancer cells but not spheroids. Not enough cancer targeting. No change in cell morphology in monolayer or spheroids.
HAP-P-Pip9.3-GA-FA—Pip-loaded HAP modified with phosphonate, coated with gum Arabic, and conjugated to folic acid		Long-term release. Release 100% of Pip capacity ~84 h (pH 6.8) and 72 h (pH 5).	Less cytotoxicity. High anticancer effect with full inhibition of monolayer HCT116 cells and ~60% inhibition for spheroids. High cancer-targeting of monolayer and spheroid HCT116 cells. Cancer targeting through folate receptors. Cell morphology changes: smaller size, shrinkage, and defragmentation of spheroids.