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Molecular dynamics simulations using a modified Drieding 2.21 force field were carried out to study the coalescence behavior of nanometer-sized water droplets in vacuum and in n-heptane. The coalescence mechanisms of the water droplets in the above-noted environments are fairly similar in a sense that the water droplets form a bridge linking the droplets before they merge. However, in the latter situation, due to the presence of n-heptane molecules in between the water droplets, the coalescence was observed to be slowed down considerably, especially in the first 10 ps of the process. However, once the bridge is formed, the water droplets, in both situations, spend about the same amount of time to form a single droplet. The maximum distance between the droplets above which coalescence does not occur was found to be 10 A. In terms of the dynamics, the diffusion coefficient of n-heptane in the emulsion system was very close to its value in the pure liquid form. This may be because n-heptane is the continuous phase. Nonetheless, the dynamic behavior of water in n-heptane is different from that of pure water during and after the coalescence. In particular, the self-diffusion coefficient of water molecules in n-heptane is about 20% higher than the experimental value of pure water. Due to the lack of strong attraction forces between water and n-heptane molecules, the n-heptane molecules were observed to orient themselves perpendicularly to the water/n-heptane interfaces so that the contacting area is minimized.

Molecular dynamics (MD) simulation was used to study the roles of nonpolar and polar intermolecular interactions in the improvement of the drug loading capacity of poly(ethylene oxide)-b-poly(epsilon-caprolactone) (PEO-b-PCL) with increasing PCL content for two water insoluble anticancer drugs: Cucurbitacin B (CuB) and Cucurbitacin I (CuI). In particular, random binary mixture models containing 10-12 wt % drug and remaining PEO-b-PCL with three different PCL/PEO (w/w) ratios (0.5, 1, and 2) were used to calculate their Flory-Huggins interaction parameters (chi). The MD simulation results show that, for both CuB and CuI, the computed chi decreases (i.e., affinity increases) with increasing PCL/PEO ratio. Such results are consistent with our experimental observation that increasing the PCL/PEO (w/w) ratio from 1 to 4.8 significantly increases the drug loading capacity of micelles formed by PEO-b-PCL for both drugs. Analysis of the energy data shows that increasing affinity (loading) at higher PCL/PEO ratio is attributed to the increase in favorable polar interactions and to the formation of additional hydrogen bonds (H-bonds) between the drugs and the PCL block rather than to the increase in the hydrophobic characteristics of the diblock copolymer as one would normally expect. In fact, the nonpolar intermolecular interactions became more unfavorable at higher PCL/PEO ratio. Analysis of the radial distribution functions of the model mixtures indicates that at high PCL/PEO ratio, multiple H-bond sites on the PCL block interacted with single H-bond sites on the drug molecules. However, at low PCL/PEO ratio, only single H-bonds formed between various H-bond sites on the drug molecules and those of the PCL and PEO blocks. It seems that formation of H-bonds between multiple H-bond sites on the PCL block and single H-bond sites on the drug molecules is responsible for inducing drug/PEO-b-PCL affinity. The finding also explains the experimental observation that release rates of both drugs decrease with increasing PCL/PEO ratio and that the decrease in the release rate of CuB is more pronounced than that of CuI. Our simulation results show that the number of H-bonds formed between CuB and the PCL block is much higher than that of CuI at high PCL/PEO ratio.

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