Fluorosurfactants for medical nanoemulsions, their surface-active and biological properties.

Nano- and microemulsions have found various applications in pharmaceutical and medical areas both in research field as well as in applied solutions for drug delivery or diagnostic agents. However, production of stable and bio- / hemocompatible nanoemulsions are still challenging. New group of ionic surfactants have been synthesized with perfluorohexyl- or perfluorooctyl-groups as hydrophobic tail. The CMC and the parametres of the O/W emulsion (the particle size distribution and the zeta-potential) were determined. The influence of the surfactants on in vitro proliferation of human endothelial cell lines HMEC-1, murine fibroblasts L929 and hemolysis were investigated as characteristic for biocompatibility. Three candidates of surfactants were selected for pre-clinical tests on a small animal model (adult Sprague Dawley rats) on the basis of preliminary studies. This allowed to obtain nanoemulsions with narrow droplets size (average droplet diameter 141-147 nm with PDI index 0.059 - 0.065) and showed better stability over time in comparison to the commercially available surfactants. Neither cytotoxic nor hemolytic potential were observed during incubation of obtained fluorosurfactans with model cell lines L929 and HMEC-1 (average cell viability above 85 % after incubation with 1% solutions) and erythrocytes (hemolysis rate below 3.1 % for all 0.5 % solutions). During acute toxicity test on rat model, it was found that all three tested surfactant solutions showed no significant differences in controlled parameters and survival rate with control group (p > 0.05). Presented surfactants are dedicated but not limited to emulsification of organic fluorocompounds.

Effective Targeting of Colon Cancer Cells with Piperine Natural Anticancer Prodrug Using Functionalized Clusters of Hydroxyapatite Nanoparticles.

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.

Folic acid-conjugated mesoporous silica particles as nanocarriers of natural prodrugs for cancer targeting and antioxidant action.

Naturally derived prodrugs have a wide range of pharmacological activities, including anticancer, antioxidant, and antiviral effects. However, significant barriers inhibit their use in medicine, e.g. their hydrophobicity. In this comprehensive study, we investigated simple and effective nanoformulations consisting of amine-functionalized and conjugated with folic acid (FA) mesoporous silica nanoparticles (MSNs). Two types of MSNs were studied: KCC- 1, with mean size 324 nm and mean pore diameter 3.4 nm, and MCM - 41, with mean size 197 and pore diameter 2 nm. Both types of MSNs were loaded with three anticancer prodrugs: curcumin, quercetin, and colchicine. The nanoformulations were tested to target in vitro human hepatocellular carcinoma cells (HepG2) and HeLa cancer cells. The amine-functionalized and FA-conjugated curcumin-loaded, especially KCC-1 MSNs penetrated all cells organs and steadily released curcumin. The FA-conjugated MSNs displayed higher cellular uptake, sustained intracellular release, and cytotoxicity effects in comparison to non-conjugated MSNs. The KCC-1 type MSNs carrying curcumin displayed the highest anticancer activity. Apoptosis was induced through specific signaling molecular pathways (caspase-3, H2O2, c-MET, and MCL-1). The nanoformulations displayed also an enhanced antioxidant activity compared to the pure forms of the prodrugs, and the effect depended on the time of release, type of MSN, prodrug, and assay used. FA-conjugated MSNs carrying curcumin and other safe natural prodrugs offer new possibilities for targeted cancer therapy.