Molecular Dynamics Study of the Diffusivity of a HydrophobicDrug Cucurbitacin B in Pseudo-poly(ethylene oxide-b-caprolactone) Micelle Environments.

Isobaric–isothermalmolecular dynamics simulation was usedto study the diffusion of a hydrophobic drug Cucurbitacin B (CuB)in pseudomicelle environments consisting of poly(ethylene oxide-b-caprolactone) (PEO-b-PCL) swollen byvarious amounts of water. Two PEO-b-PCL configurations,linear and branched, with the same total molecular weight were used.For the branched configuration, the block copolymer contained onelinear block of PEO with the same molecular weight as that of thePEO block used in the linear configuration but with one end connectingto three PCL blocks with the same chain length, hereafter denotedPEO-b-3PCL. Regardless of the configuration, thesimulation results showed that the diffusivity of CuB was insensitiveto the water concentration up to ∼8 wt % while that of waterdecreased with an increasing water concentration. The diffusivityof CuB (10–8cm2/s) was 3 orders of magnitudelower than that of water (10–5cm2/s).This is attributed to the fact that CuB relied on the wiggling motionof the block copolymers to diffuse while water molecules diffusedvia a hopping mechanism. The rates at which CuB and water diffusedinto PEO-b-PCL were twice those in PEO-b-3PCL because the chain mobility and the degree of swelling are higherand there are fewer intermolecular hydrogen bonds in the case of PEO-b-PCL. The velocity autocorrelation functions of CuB showthat the free volume holes formed by PEO-b-3PCL aremore rigid than those formed by PEO-b-PCL, makingCuB exhibit higher-frequency collision motion in PEO-b-3PCL than in PEO-b-PCL, and the difference in frequencyis insensitive to water concentration. [ABSTRACT FROM AUTHOR]