Liposomes, as a class of biological nanocarriers, play a key role in modern drug delivery, particularly in cancer therapy. However, controlling their polydispersity index (PDI), a critical parameter influencing liposome performance, remains a challenge. In this study, an analytical model was developed to predict the PDI of liposomes, offering a cost-effective and time-saving alternative to conventional experimental methods such as dynamic light scattering (DLS). The proposed model is grounded in the Gibbs free energy framework, incorporating the bending energy of phospholipid bilayers, the free edge energy, and entropic effects arising from the configurations and dispersion of phospholipid molecules in aqueous solution. Consequently, this analytical framework provides higher accuracy in calculating PDI compared to previous models that neglected entropic contributions. To validate the formulated model, a micromixer was designed and fabricated for liposome production. The synthesized liposomes were characterized using a Zetasizer and DLS technique. The model predicted PDI values of 0.182 and 0.205 for total lipid concentrations of 10 and 20 mol/m3, respectively, with relative errors of 8.91% and 10.52% compared to experimental data. Given the molecular complexities governing liposome formation and the limitations of analytically modeling all associated phenomena, these results are considered satisfactory. Overall, the presented model serves as an effective tool for predicting liposome PDI in drug delivery applications.

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