1. Department of Chemistry, Faculty of Science, Vali-e-Asr University of Rafsanjan, Rafsanjan, Iran
Abstract
Introduction
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. 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. the most commonly used methods for measuring in-vitro drug releasing from drug carriers can be grouped into three broad categories: sample and separate methods (ss), continuous flow (cf) and dialysis. while these techniques are capable of measuring release profile, they usually involve complicated procedures and require labor-intensive sample preparation. the sample preparation time for these techniques prohibits repetitive measurements at short time intervals. therefore, these methods cannot monitor directly the real-time drug releasing, as desired for obtaining the most accurate drug release kinetics profile. the paper reports a simple electrochemical method to directly monitor the drug-release profile of dosage forms, 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 a glassy carbon electrode (gce). releasing of doxorubicin from liposome results in systematic increasing in free doxorubicin. once the concentration of doxorubicin increases in the cell, a rise in the current signal of amperometry is observed. drug release was conducted using the mpa system in serum sample and under different phs.
Methods
The release medium in amperometric cell consisted of 1x pbs buffer and the ph of the release media was adjusted with 0.1 mol l–1 hcl and/or naoh solution. 100 µl of caelyx® (2.0 mg ml–1 vial) was added to 5.0 ml of the release media. then the cell was warmed at 37 °c by putting it into a water bath at 37 °c. the in-vitro drug release behavior from the doxorubicin-loaded liposomes was determined using mpa. the optimized sequential potential pulses were continuously applied to the working electrode and the doxorubicin amperometric signal was monitored at the first two potential pulses.
Results
Chronomperometric (i–t) curve (for potential pulse of –0.60 v) of the released doxorubicin from liposomes at phs 7.4 and 5.0 at the gce was obtained. releasing of doxorubicin from nanoparticles results in systematic increase in free doxorubicin. once concentration of doxorubicin increases in the cell, arise in the current signal of amperometry is observed. indeed, amperometric i–t curve of liposomal doxorubicin demonstrates doxorubicin-release profile from the liposome. the fraction of doxorubicin released at ph of 7.4 was ∼ 0.1 as compared to ∼0. 2 at ph of 5.0 after the 60 min over which the release kinetics was examined. in another study, the release profile of doxorubicin due to a step change in ph was illustrated. the ph of the medium was changed from 7.4 to 5.0. at ph 7.4, the liposome is in a more compact state, hence the rate and amount of released doxorubicin is low at this ph regime. when the ph was decreased to 5.0, we observed a rapid increasing in the amperometric current signal due to increasing in porosity of the matrix and releasing rate of doxorubicin. we then measured the continuous releasing of doxorubicin from liposomes in 33% serum solution (ph 7.4). the results showed the releasing of doxorubicin is much slower in 33% serum than in the pbs buffer. these results are consistent with those reported in the literature.
Conclusion
The obtained results confirmed that the mpa is a good alternative method to the other existing techniques for monitoring the drug release profile. the proposed method presents a wide working linear range and a low limit of detection, allowing for studies of highly diluted samples and therefore, a decreasing in occasional interferences in the matrix.
Keywords
Drug release profile, electrochemistry, nanoparticles
