PLGA nanoparticles are one of the most investigated drug delivery systems among all polymeric nanoparticles. Although there are several successfully developed and marketed microparticulate PLGA systems, unfortunately, there was little progress in the in vitro to clinic and marketing translation of PLGA nanoparticulate systems. One of the main reasons is the very low drug-loading capacity of PLGA nanoparticles. This situation becomes more problematic in some drugs such as doxorubicin. Doxorubicin is a very interesting molecule whose solubility and characteristics dramatically change depending on pH and the presence of various ions and compounds in the medium. This property of the doxorubicin probably directly influences the drug loading of the doxorubicin to PLGA nanoparticles. In this study, it was aimed to improve the doxorubicin loading to PLGA nanoparticles while the average particle size and polydispersity index are in the acceptable ranges.

TOPSIS-based Taguchi experimental design was adopted and the effect mainly water phase additive on drug loading, encapsulation efficiency, particle size, and polydispersity index were investigated.

Results show that generally using PBS and HEPES improves the overall results when compared with blank water as the water phase.

Within the study, TOPSIS-based Taguchi design was successfully applied to the optimization of a PLGA nanoparticle formulation, and the optimum water phase additive was determined. These findings will be very beneficial to the researcher in the field of doxorubicin-loaded PLGA nanoparticles in their future studies.