Magnolol and Honokiol: Two Natural Compounds with Similar Chemical Structure but Different Physicochemical and Stability Properties.

Magnolia spp. extracts are known for their use in traditional Korean, Chinese, and Japanese medicine in the treatment of gastrointestinal disorders, anxiety, and allergies. Among their main components with pharmacological activity, the most relevant are magnolol and honokiol, which also show antitumoral activity. The objectives of this work were to study some physicochemical properties of both substances and their stability under different conditions of temperature, pH, and oxidation. Additionally, liposomes of honokiol (the least stable compound) were formulated and characterized. Both compounds showed pH-dependent solubility, with different solubility-pH profiles. Magnolol showed a lower solubility than honokiol at acidic pH values, but a higher solubility at alkaline pH values. The partition coefficients were similar and relatively high for both compounds (log Po/w ≈ 4.5), indicating their lipophilic nature. Honokiol was less stable than magnolol, mainly at neutral and basic pH values. To improve the poor stability of honokiol, it was suitably loaded in liposomes. The obtained liposomes were small in size (175 nm), homogeneous (polydispersity index = 0.17), highly negatively charged (-11 mV), and able to incorporate high amounts of honokiol (entrapment efficiency = 93.4%). The encapsulation of honokiol in liposomes increased its stability only at alkaline pH values.