In this research, layered double hydroxides (LDH) are proposed as drug delivery vehicles due to their ability to enhance the therapeutic effects of active pharmaceutical ingredients while potentially reducing toxicity. Doxorubicin (DOX) and 5-Fluorouracil (5-FU) are among the most widely studied and applied antitumor agents because of their broad-spectrum activity against various types of cancer. However, both drugs exhibit several limitations, including low plasma bioavailability, poor solubility, and slow systemic clearance. As a result, only a small fraction of the administered drug reaches the tumor cells, often causing significant side effects in patients. To address these drawbacks, LDH are explored as nanocarriers to improve delivery efficiency.

The most common drug-loading approach involves incorporating LDH particles into DOX and 5-FU solutions. In this study, three synthesis methods—anion exchange, coprecipitation, and mechanochemical synthesis—were employed to evaluate the structural stability of the carriers and the amount of drug retained. Two common LDH compositions, Mg/Al and Zn/Al, were used due to their biomedical relevance. The resulting LDH and LDH/drug hybrids were characterized using solid-state techniques such as XRD, FTIR, EPR, Raman, and EDS; complemented with a computational analysis to elucidate the structure and types of interactions, as well as to predict a UV–Vis spectrum for the release profile.

The Zn/Al LDH structure degraded during drug loading, while Mg/Al LDH particles remained structurally stable under all three loading methods. Notably, the mechanochemical method achieved the highest DOX loading capacity and proved to be the simplest and least aggressive of the three approaches.