Predicting drug release kinetics from nanocarriers inside dialysis bags

Dialysis methods are frequently used to determine the in vitro drug release kinetics of nanoparticle drug delivery systems. However, the need for the released drug to diffuse through the dialysis membrane delays its appearance in the sampling compartment. Thus, the apparent drug release data outside the dialysis bag typically does not match the desired release kinetics inside the bag adjacent to the nanocarriers. To address this issue, here we describe a simple approach to determine the actual drug release kinetics from nano drug carriers inside the dialysis bag from the experimental data measured from the sampling compartment. First, a calibration experiment is carried out to determine the diffusion barrier properties of the dialysis membranes. The apparent drug release profile of the nanocarrier is then determined using the dialysis method, and a mathematical model is applied to determine the actual drug release kinetics from the experimental data. The model was tested on DOXIL® (doxorubicin liposomes), and an excellent agreement was found between the predicted and measured drug concentration inside the dialysis membranes. By taking the barrier effects of dialysis membranes into consideration, our model independent of drug carrier not only enables the proper interpretation of the data from dialysis studies but also helps to evaluate the dialysis methodology applied to in vitro drug release assays.