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Intermolecular interactions of drug molecules can lead to aggregation, which has a significant impact on their application. This problem might escape the attention when studying their solubility as small aggregates might behave almost as single molecules. We studied the aggregation behaviour of doxorubicin (DOX) molecules through density functional (DFT) methods and molecular dynamics (MD) simulations in water, dimethylformamide (DMF), ethanol (EtOH), and dimethyl sulfoxide (DMSO). We described the degree of aggregation by MD-calculated radial distribution function, combined radial/angular distribution functions, autocorrelation functions, and the number of hydrogen bonds of individual DOX and solvent atoms. MD-calculated diffusion coefficients for DOX decrease along the series water > DMF > EtOH > DMSO (0.101 × 10−9, 0.047 × 10−9, 0.025 × 10−9, and 0.007 × 10−9 m2 s−1, respectively) consistent with increasing aggregation found in the MD simulations. These aggregates have different characters, depending on the DOX⋯solvent interactions, and include hydrogen bonding and π-stacking. Even though the solvation energy of a single DOX molecule in DMSO (−24.8 kcal mol−1) is higher than in other solvents, the formation of larger aggregates in this solvent prevents proper solvation. Further, the orientation of doxorubicin molecules at octanol/water and dipalmitoylphosphatidylcholine (DPPC)/water interfaces was studied with two different orientations from the bivariate maps. In the case of the DPPC/water interface, the anthracycline part points toward the aqueous phase, while this part is oriented almost parallel to the octanol/water interface in DMSO. [ABSTRACT FROM AUTHOR]

Drug delivery systems sensitive to pH have been investigated recently as a responsive strategy for tumour targeting in view of the slightly acidic pH environment of most solid tumours. Herein, we report Zn capped Al2O3 and TiO2 nanoporous arrays for pH sensitive drug release. The nanostructures were fabricated through electrochemical anodisation. Vitamin C as a model drug was loaded into the nanopores; some were then capped using elemental Zn. The release rates of vitamin C were investigated in water or lactic acid using high performance liquid chromatography (HPLC). The amount of drug loaded into the nanostructures was about 7 times higher for TiO2 compared with Al2O3 and the release was faster from TiO2. Zn capping proved to be quite efficient at preventing release at high pH (7) and not largely hindering the release at low pH (5), making both systems suitable for pH-triggered release. Molecular dynamics (MD) simulations showed that the diffusion of vitamin C molecules through the model nanopores is faster for TiO2 than for Al2O3, consistent with the experimental results. The tremendously stronger H bonding interactions observed for vitamin C molecules and water molecules with the TiO2 walls compared with Al2O3 are responsible for the observed differences in the calculated number density profiles and radial distribution functions. [ABSTRACT FROM AUTHOR]