Targeted drug delivery offers great opportunities for treating cancer. Here, we developed a novel anticancer targeted delivery system for piperine (Pip), an alkaloid prodrug derived from black pepper that exhibits anticancer effects. The tailored delivery system comprises aggregated hydroxyapatite nanoparticles (HAPs) functionalized with phosphonate groups (HAP-Ps). Pip was loaded into HAPs and HAP-Ps at pH 7.2 and 9.3 to obtain nanoformulations. The nanoformulations were characterized using several techniques and the release kinetics and anticancer effects investigated in vitro. The Pip loading capacity was >20%. Prolonged release was observed with kinetics dependent on pH, surface modification, and coating. The nanoformulations fully inhibited monolayer HCT116 colon cancer cells compared to Caco2 colon cancer and MCF7 breast cancer cells after 72 h, whereas free Pip had a weaker effect. The nanoformulations inhibited ~60% in HCT116 spheroids compared to free Pip. The Pip-loaded nanoparticles were also coated with gum Arabic and functionalized with folic acid as a targeting ligand. These functionalized nanoformulations had the lowest cytotoxicity towards normal WI-38 fibroblast cells. These preliminary findings suggest that the targeted delivery system comprising HAP aggregates loaded with Pip, coated with gum Arabic, and functionalized with folic acid are a potentially efficient agent against colon cancer.

Handling and properties of nanoparticles strongly depend on processes that take place on their surface. Specific surface area and adsorption capacity strongly increase as the nanoparticle size decreases. A crucial factor is adsorption of water from ambient atmosphere. Considering the ever-growing number of hydroxyapatite nanoparticles applications, we decided to investigate how the size of nanoparticles and the changes in relative air humidity affect adsorption of water on their surface. Hydroxyapatite nanoparticles of two sizes: 10 and 40 nm, were tested. It was found that the nanoparticle size has a strong effect on the kinetics and efficiency of water adsorption. For the same value of water activity, the quantity of water adsorbed on the surface of 10 nm nano-hydroxyapatite was five times greater than that adsorbed on the 40 nm. Based on the adsorption isotherm fitting method, it was found that a multilayer physical adsorption mechanism was active. The number of adsorbed water layers at constant humidity strongly depends on particles size and reaches even 23 layers for the 10 nm particles. The amount of water adsorbed on these particles was surprisingly high, comparable to the amount of water absorbed by the commonly used moisture-sorbent silica gel.