Description
Copper–dithiocarbamate complexes (Cu-DTC) have demonstrated the ability to induce cell death in certain tumor cell lines, making them potential candidates for the development of new anticancer treatments. However, their clinical application is limited by poor water solubility, which negatively affects bioavailability and drug delivery. To overcome this limitation, the present study investigates the encapsulation of Cu-DTC complexes within liposomes, aiming to enhance solubility and stability, and achieve a controlled and effective release of the active compound.
The study was developed in several phases. Initially, three copper complexes, namely Cu(DASD)2, Cu(DEDC)2, and Cu(DBODC)2, were synthesized and characterized by infrared (IR) and elemental analysis. The solubility studies revealed that the copper complex with DASD ligands was insoluble, while the one with DEDC ligands was soluble but only at low concentrations, and the complex with DBODC ligands showed better solubility. Consequently, only the latter two complexes were selected for further experiments.
A preliminary encapsulation of these two complexes into liposomes made by phosphatidylcholine (PC) was performed using the ethanol injection technique to evaluate both the size of the liposomes and the amount of loaded active substance. The size of the liposomes increased slightly in the presence of the active compound. The encapsulation capacity of the Cu(DEDC)₂ complex determined by UV analysis was found to be very low, making it unsuitable for further studies, while the Cu(DBODC)2 complex resulted in sufficient encapsulation efficiency to justify its use in subsequent experiments.
Afterwards, the study was transferred to the microfluidic system. Empty liposomes were produced by varying lipid concentration, FRR and TFR parameters. Then, Cu(DBODC)2 complex was added to the selected formulations, showing an average size less than 200 nm with a slightly increase over time. The encapsulation of the active compound determined by filter centrifugation followed by UV analysis reached 80% of drug loading.
Finally, Franz diffusion cells experiment using a cellulose membrane and H₂O:EtOH (50:50 v/v) as the receiving phase at 37 °C, were conducted to evaluate the release of the active ingredient. The formulations were tested and compared with the copper complex dissolved in ethanol at the same concentration. Samples were collected for eight hours and analyzed by UV spectroscopy. The free complex in ethanol did not diffuse through the membrane, instead accumulating on its surface, as evidenced by yellow colour. The diffusion of the encapsulated complex from liposomes showed a biphasic release profile, with a rapid initial phase up to 2 hours, followed by stabilization with approximately 20–40% drug released after 6–8 hours.