All-Atom Molecular Dynamics Study of a Spherical Micelle Composed of N-Acetylated Poly(ethylene glycol)−Poly(γ-benzyl <scp>l</scp>-glutamate) Block Copolymers: A Potential Carrier of Drug Delivery Systems for Cancer

Kuramochi, Hiroshi; Andoh, Yoshimichi; Yoshii, Noriyuki; Okazaki, Susumu

doi:10.1021/jp906155z

Cited by 36 publications

(20 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MD and Monte Carlo (MC) simulations have been applied to simulate drug-excipient interactions 54 , 55 and nanoparticle formation. 56 , 57 , 58 A computational approach to dock drug molecules into a polymer matrix provides molecular level information on drug-matrix interaction in the random polymer aggregates 57 , 59 or dendrimer systems. 60 , 61 In fact, there is no such virtually empty pocket pre-existing in polymer aggregates for the drug molecule to diffuse in.…”

Section: Discussionmentioning

confidence: 99%

A drug-specific nanocarrier design for efficient anticancer therapy

et al. 2015

View full text Add to dashboard Cite

The drug-loading properties of nanocarriers depend on the chemical structures and properties of their building blocks. Here, we customize telodendrimers (linear-dendritic copolymer) to design a nanocarrier with improved in vivo drug delivery characteristics. We do a virtual screen of a library of small molecules to identify the optimal building blocks for precise telodendrimer synthesis using peptide chemistry. With rationally designed telodendrimer architectures, we then optimize the drug binding affinity of a nanocarrier by introducing an optimal drug-binding molecule (DBM) without sacrificing the stability of the nanocarrier. To validate the computational predictions, we synthesize a series of nanocarriers and evaluate systematically for doxorubicin delivery. Rhein-containing nanocarriers have sustained drug release, prolonged circulation, increased tolerated dose, reduced toxicity, effective tumor targeting and superior anticancer effects owing to favourable doxorubicin-binding affinity and improved nanoparticle stability. This study demonstrates the feasibility and versatility of the de novo design of telodendrimer nanocarriers for specific drug molecules, which is a promising approach to transform nanocarrier development for drug delivery.

show abstract

Section: Discussionmentioning

confidence: 99%

A drug-specific nanocarrier design for efficient anticancer therapy

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Recently, drug-delivery systems using micelles to transport drugs have been actively developed. [7][8][9] In synthetic chemistry, synthesis is sometimes performed within reactant-solubilizing micelles. 13,14 Solubilization is often used in biochemistry to extract water-insoluble membrane proteins from cells.…”

Section: Introductionmentioning

confidence: 99%

Free energy profiles for penetration of methane and water molecules into spherical sodium dodecyl sulfate micelles obtained using the thermodynamic integration method combined with molecular dynamics calculations

Fujimoto

Yoshii

Okazaki

2012

The Journal of Chemical Physics

View full text Add to dashboard Cite

Free energy profiles for penetration of methane and water molecules into spherical sodium dodecyl sulfate micelles obtained using the thermodynamic integration method combined with molecular dynamics calculations K. Fujimoto Science, Nagoya University, Japan (Received 14 October 2011; accepted 5 December 2011; published online 6 January 2012) The free energy profiles, G(r), for penetration of methane and water molecules into sodium dodecyl sulfate (SDS) micelles have been calculated as a function of distance r from the SDS micelle to the methane and water molecules, using the thermodynamic integration method combined with molecular dynamics calculations. The calculations showed that methane is about 6-12 kJ mol −1 more stable in the SDS micelle than in the water phase, and no G(r) barrier is observed in the vicinity of the sulfate ions of the SDS micelle, implying that methane is easily drawn into the SDS micelle. Based on analysis of the contributions from hydrophobic groups, sulfate ions, sodium ions, and solvent water to G(r), it is clear that methane in the SDS micelle is about 25 kJ mol −1 more stable than it is in the water phase because of the contribution from the solvent water itself. This can be understood by the hydrophobic effect. In contrast, methane is destabilized by 5-15 kJ mol −1 by the contribution from the hydrophobic groups of the SDS micelle because of the repulsive interactions between the methane and the crowded hydrophobic groups of the SDS. The large stabilizing effect of the solvent water is higher than the repulsion by the hydrophobic groups, driving methane to become solubilized into the SDS micelle. A good correlation was found between the distribution of cavities and the distribution of methane molecules in the micelle. The methane may move about in the SDS micelle by diffusing between cavities. In contrast, with respect to the water, G(r) has a large positive value of 24-35 kJ mol −1 , so water is not stabilized in the micelle. Analysis showed that the contributions change in complex ways as a function of r and cancel each other out. Reference calculations of the mean forces on a penetrating water molecule into a dodecane droplet clearly showed the same free energy behavior. The common feature is that water is less stable in the hydrophobic core than in the water phase because of the energetic disadvantage of breaking hydrogen bonds formed in the water phase. The difference between the behaviors of the SDS micelles and the dodecane droplets is found just at the interface; this is caused by the strong surface dipole moment formed by sulfate ions and sodium ions in the SDS micelles.

show abstract

“…[1][2][3][4][5][6] Drug delivery systems by micelles have also been developed. [7][8][9] For scientific research, water-insoluble membrane proteins were extracted from cell membranes using the protein solubilization to the micelle. [10][11][12] Furthermore, highly selective and efficient syntheses are performed in the reactant-solubilizing micelles.…”

Section: Introductionmentioning

confidence: 99%

Molecular dynamics study of free energy of transfer of alcohol and amine from water phase to the micelle by thermodynamic integration method

Fujimoto

Yoshii

Okazaki

2012

The Journal of Chemical Physics

View full text Add to dashboard Cite

Free energy of transfer of methylamine, octylamine, methanol, and octanol from water phase to sodium dodecyl sulfate (SDS) micelle has been calculated using thermodynamic integration method combined with molecular dynamics calculations. Together with the results for alkanes obtained in our previous study [K. Fujimoto, N. Yoshii, and S. Okazaki, J. Chem. Phys. 133, 074511 (2010)], the effect of polar group on the partition of hydrophilic solutes between water phase and the micelle has been investigated in detail at a molecular level. The calculations showed that the molecules with octyl group are more stable in the SDS micelle than in the water phase due to their hydrophobicity of long alkyl chain. In contrast, methanol and methylamine are stable in the water phase as well as in the micelle because of their high hydrophilicity. The spatial distribution of methylamine, octylamine, methanol, and octanol has also been evaluated as a function of the distance, R, from the center of mass of SDS micelle to the solutes. The distribution shows that the methylamine molecule is adsorbed on the SDS micelle surface, while the methanol molecule is delocalized among the whole system, i.e., in the water phase, on the surface of the micelle, and in the hydrophobic core of the micelle. The octylamine and octanol molecules are solubilized in the SDS micelle with palisade layer structure and are not found in the water phase.

show abstract

All-Atom Molecular Dynamics Study of a Spherical Micelle Composed of N-Acetylated Poly(ethylene glycol)−Poly(γ-benzyl l-glutamate) Block Copolymers: A Potential Carrier of Drug Delivery Systems for Cancer

Cited by 36 publications

References 41 publications

A drug-specific nanocarrier design for efficient anticancer therapy

A drug-specific nanocarrier design for efficient anticancer therapy

Free energy profiles for penetration of methane and water molecules into spherical sodium dodecyl sulfate micelles obtained using the thermodynamic integration method combined with molecular dynamics calculations

Molecular dynamics study of free energy of transfer of alcohol and amine from water phase to the micelle by thermodynamic integration method

Contact Info

Product

Resources

About