Abstract:
For the construction of an effective drug delivery system using nanoparticles as drug carriers, understanding the kinetics of drug carriers as well as encapsulated drugs is essential. It is important to keep in mind that drug entrapped in nanoparticles such as liposomes is not bioavailable; it only becomes bioavailable when it is released. Hence the ability of accumulated drug carriers to increase the local bioavailable drug concentrations, and increase the therapeutic outcome, only occurs when the rate of release of entrapped drug from the nanoparticles is optimized. The drug must be delivered to the disease site and become bioavailable at a level within its therapeutic window and at a sufficient rate, for a sufficient period, to have optimal therapeutic activity. The activity of cell cycle-specific drugs can be acutely sensitive to rates of release and it is now possible to design carriers with release rates that are tunable to the requirements of the therapeutic application. Ideally, a successful nanoparticulate system as a drug carrier should have a high drug loading capacity thereby reducing the quantity of matrix material for administration and a controlled release drug delivery to achieve the correct dose of drug at only the disease site with the most effective release profile. Therefore, controlling the rate of drug release from carriers is essential for optimum drug delivery.
In order to evaluate the drug-release behavior from therapeutic nanoparticles a simple electrochemical method was used to directly assess the drug-release profile, thereby eliminating the intermediate process step. The method is based on the multiple pulse amperometric (MPA) measurement of the oxidation and reduction of doxorubicin released from liposome at multiwall carbon nanotubes (MWCNTs)-modified glassy carbon electrode (GCE). The method consists on the application of three sequential potential pulses as a function of time. Released doxorubicin is detected at +0.60 and –0.60 V by two different oxidation and reduction processes, respectively. The third potential pulse (–1.00 V) is applied for the regeneration (cleaning) of the surface of the mofdified-GCE. Releasing of doxorubicin from liposome results in systematic increasing in free doxorubicin. Once concentration of doxorubicin increases in cell, a rise in current signal of amperometry is observed. Drug release was conducted using the MPA system in serum sample and under different pHs. Finally the accuracy of the proposed method was evaluated by comparing of the results with dialysis (with a UV detection) method.