Abstract:
Liposomes are widely used as nanocarriers in cancer therapy due to their ability to
encapsulate chemotherapeutic agents and modulate drug release. Among these, doxorubicin-loaded
liposomes, such as Doxil®, have demonstrated enhanced safety and efficacy profiles. However, predicting
the kinetics of drug leakage remains critical for optimizing liposome design and therapeutic performance.
In this study, a first-order mathematical model based on Fick’s law of diffusion was developed to predict
the leakage kinetics of doxorubicin from liposomes. The model captures key behaviors, including the
effects of liposome size and lipid composition on membrane permeability and leakage. Simulations show
that lower permeability coefficients, associated with increased membrane rigidity, slow down drug
leakage, whereas smaller liposomes exhibit faster leakage due to their higher surface-area-to-volume
ratios. Despite its simplicity, the model successfully captures experimental trends, reproduces
permeability coefficients on the same order of magnitude as those observed in other doxorubicin-loaded
liposomal systems, and demonstrates robustness to minor structural variations. It serves as a practical
tool for early-stage design of liposomal drug delivery systems and highlights the sensitivity of drug leakage
to key formulation parameters.
