Exploring the drug-lipid interaction of weak-hydrophobic drug loaded solid lipid nanoparticles by isothermal titration calorimetry

Abstract

Drug-lipid interaction was a vital issue for weak-hydrophobic drug-loaded solid lipid nanoparticles (WHD-SLNs). With a weak drug-lipid interaction, the drug loading capacity and physical stability could be low, and thus the drug-lipid interaction should be investigated. This paper was aimed to explore the drug-lipid interactions of WHD-SLNs by isothermal titration calorimetry (ITC). Benzoic acid (BEA) and salicylic acid (SAA) were chosen as the model weak-hydrophobic drugs, and stearic acid (SA) was selected as the model lipid material. For reference, the melting point depression (the proof of molecular interaction) of BEA-SA system and SAA-SA system was explored by differential scanning calorimetry (DSC) and hot stage polarized-light microscopy (HSPM). The ITC results demonstrated that BEA-SA interaction had negative ΔH and negative ΔS, while SAA-SA interaction possessed slightly negative ΔH and positive ΔS. It was indicated that the major interactions in BEA-SA interaction and SAA-SA interaction were hydrogen bonds and hydrophobic forces, respectively. Shown by DSC and HSPM results, the melting point depression in BEA-SA system was more significant than SAA-SA system. Therefore, melting point depression was mainly associated with hydrogen bond interactions, rather than hydrophobic forces. This study could provide new insight for the interpretation of drug-lipid interaction of WHD-SLNs.