Assessment of Drug Delivery Systems from Molecular Dynamic Perspective
In this study, we developed and simulated nano-drug delivery systems efficacy in compare to free drug prescription. Computational models can be utilized to accelerate experimental steps and control the experiments high cost. Molecular dynamics simulation (MDS), in particular NAMD was utilized to better understand the anti-cancer drug interaction with cell membrane model. Paclitaxel (PTX) and dipalmitoylphosphatidylcholine (DPPC) were selected for the drug molecule and as a natural phospholipid nanocarrier, respectively. This work focused on two important interaction parameters between molecules in terms of center of mass (COM) and van der Waals interaction energy. Furthermore, we compared the simulation results of the PTX interaction with the cell membrane and the interaction of DPPC as a nanocarrier loaded by the drug with the cell membrane. The molecular dynamic analysis resulted in low energy between the nanocarrier and the cell membrane as well as significant decrease of COM amount in the nanocarrier and the cell membrane system during the interaction. Thus, the drug vehicle showed notably better interaction with the cell membrane in compared to free drug interaction with the cell membrane.
 Shi, J., et al., Nanotechnology in drug delivery and tissue engineering: from discovery to applications. Nano letters, 2010. 10(9): p. 3223-3230.
 Gupta, U., et al., A review of in vitro–in vivo investigations on dendrimers: the novel nanoscopic drug carriers. Nanomedicine: Nanotechnology, Biology and Medicine, 2006. 2(2): p. 66-73.
 Svenson, S., Dendrimers as versatile platform in drug delivery applications. European Journal of Pharmaceutics and Biopharmaceutics, 2009. 71(3): p. 445-462.
 Herce, H.D. and A.E. Garcia, Molecular dynamics simulations suggest a mechanism for translocation of the HIV-1 TAT peptide across lipid membranes. Proceedings of the National Academy of Sciences, 2007. 104(52): p. 20805-20810.
 Schiff, P.B., J. Fant, and S.B. Horwitz, Promotion of microtubule assembly in vitro by taxol. 1979.
 Jordan, M.A. and L. Wilson, Microtubules as a target for anticancer drugs. Nature Reviews Cancer, 2004. 4(4): p. 253-265.
 Amos, L.A. What tubulin drugs tell us about microtubule structure and dynamics. in Seminars in cell & developmental biology. 2011. Elsevier.
 Löwe, J., et al., Refined structure of αβ-tubulin at 3.5 Å resolution. Journal of molecular biology, 2001. 313(5): p. 1045-1057.
 Mastropaolo, D., et al., Crystal and molecular structure of paclitaxel (taxol). Proceedings of the National Academy of Sciences, 1995. 92(15): p. 6920-6924.
 Balasubramanian, S.V., J.L. Alderfer, and R.M. Straubinger, Solvent‐and concentration‐dependent molecular interactions of taxol (paclitaxel). Journal of pharmaceutical sciences, 1994. 83(10): p. 1470-1476.
 Koudelka, Š. and J. Turánek, Liposomal paclitaxel formulations. Journal of Controlled Release, 2012. 163(3): p. 322-334.
 Zhang, Z., L. Mei, and S.-S. Feng, Paclitaxel drug delivery systems. Expert opinion on drug delivery, 2013. 10(3): p. 325-340.
 Gao, Y., et al., Enzyme-instructed molecular self-assembly confers nanofibers and a supramolecular hydrogel of taxol derivative. Journal of the American Chemical Society, 2009. 131(38): p. 13576-13577.
 Gratton, S.E., et al., The effect of particle design on cellular internalization pathways. Proceedings of the National Academy of Sciences, 2008. 105(33): p. 11613-11618.
 Loverde, S.M., et al., Curvature, rigidity, and pattern formation in functional polymer micelles and vesicles–From dynamic visualization to molecular simulation. Current Opinion in Solid State and Materials Science, 2011. 15(6): p. 277-284.
 Loverde, S.M., M.L. Klein, and D.E. Discher, Nanoparticle Shape Improves Delivery: Rational Coarse Grain Molecular Dynamics (rCG‐MD) of Taxol in Worm‐Like PEG‐PCL Micelles. Advanced materials, 2012. 24(28): p. 3823-3830.
 Kopeć, W., J. Telenius, and H. Khandelia, Molecular dynamics simulations of the interactions of medicinal plant extracts and drugs with lipid bilayer membranes. FEBS Journal, 2013. 280(12): p. 2785-2805.
 Loverde, S.M., Molecular simulation of the transport of drugs across model membranes. The Journal of Physical Chemistry Letters, 2014. 5(10): p. 1659-1665.
 Abu-Surrah, A.S. and M. Kettunen, Platinum group antitumor chemistry: design and development of new anticancer drugs complementary to cisplatin. Current medicinal chemistry, 2006. 13(11): p. 1337-1357.
 Dezhampanah, H., A.K. Bordbar, and S. Farshad, Thermodynamic characterization of phthalocyanine–human serum albumin interaction. Journal of Spectroscopy, 2011. 25(5): p. 235-242.
 Peetla, C., A. Stine, and V. Labhasetwar, Biophysical interactions with model lipid membranes: applications in drug discovery and drug delivery. Molecular pharmaceutics, 2009. 6(5): p. 1264-1276.
 Avila-Salas, F.n., et al., Study of interaction energies between the PAMAM dendrimer and nonsteroidal anti-inflammatory drug using a distributed computational strategy and experimental analysis by ESI-MS/MS. The Journal of Physical Chemistry B, 2012. 116(7): p. 2031-2039.
 Jämbeck, J.P., et al., Molecular Dynamics Studies of Liposomes as Carriers for Photosensitizing Drugs: Development, Validation, and Simulations with a Coarse-Grained Model. Journal of Chemical Theory and Computation, 2014. 10(1): p. 5-13.
 Kang, M. and S.M. Loverde, Molecular simulation of the concentration-dependent interaction of hydrophobic drugs with model cellular membranes. The Journal of Physical Chemistry B, 2014. 118(41): p. 11965-11972.
 Cheng, Y., Q.X. Pei, and H. Gao, Molecular-dynamics studies of competitive replacement in peptide–nanotube assembly for control of drug release. Nanotechnology, 2009. 20(14): p. 145101.
 Dai, X., et al., Effects of Concentrations on the Transdermal Permeation Enhancing Mechanisms of Borneol: A Coarse-Grained Molecular Dynamics Simulation on Mixed-Bilayer Membranes. International Journal of Molecular Sciences, 2016. 17(8): p. 1349.
 Allen, T.M. and P.R. Cullis, Drug delivery systems: entering the mainstream. Science, 2004. 303(5665): p. 1818-1822.
 Discher, D.E., et al., Emerging applications of polymersomes in delivery: from molecular dynamics to shrinkage of tumors. Progress in polymer science, 2007. 32(8): p. 838-857.
 Maruyama, K., Intracellular targeting delivery of liposomal drugs to solid tumors based on EPR effects. Advanced drug delivery reviews, 2011. 63(3): p. 161-169.
 Maeda, H., T. Sawa, and T. Konno, Mechanism of tumor-targeted delivery of macromolecular drugs, including the EPR effect in solid tumor and clinical overview of the prototype polymeric drug SMANCS. Journal of controlled release, 2001. 74(1): p. 47-61.
 Danhier, F., O. Feron, and V. Préat, To exploit the tumor microenvironment: passive and active tumor targeting of nanocarriers for anti-cancer drug delivery. Journal of Controlled Release, 2010. 148(2): p. 135-146.
 Maeda, H., H. Nakamura, and J. Fang, The EPR effect for macromolecular drug delivery to solid tumors: Improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo. Advanced drug delivery reviews, 2013. 65(1): p. 71-79.
 Yagi, K., et al., Basic study on gene therapy of human malignant glioma by use of the cationic multilamellar liposome-entrapped human interferon beta gene. Human gene therapy, 1999. 10(12): p. 1975-1982.
 Humphrey, W., A. Dalke, and K. Schulten, VMD: visual molecular dynamics. Journal of molecular graphics, 1996. 14(1): p. 33-38.
 Brooks, B.R., et al., CHARMM: the biomolecular simulation program. Journal of computational chemistry, 2009. 30(10): p. 1545-1614.
 Karplus, M., CHARMM: A program for macromolecular energy, minimization, and dynamics calculations. J Comput Chem, 1983. 4: p. 187217.
 Klauda, J.B., et al., Update of the CHARMM all-atom additive force field for lipids: validation on six lipid types. The journal of physical chemistry. B, 2010. 114(23): p. 7830.
 Vanommeslaeghe, K., et al., CHARMM general force field: A force field for drug‐like molecules compatible with the CHARMM all‐atom additive biological force fields. Journal of computational chemistry, 2010. 31(4): p. 671-690.
 Panczyk, T., et al., Sidewall Functionalization of Carbon Nanotubes as a Method of Controlling Structural Transformations of the Magnetically Triggered Nanocontainer: A Molecular Dynamics Study. The Journal of Physical Chemistry C, 2015. 119(15): p. 8373-8381.
 Xing, Y.-F., et al., Dynamic Mechanism of Single-Stranded DNA Encapsulated into Single-Wall Carbon Nanotubes: A Molecular Dynamics Simulation Study. Journal of the Physical Society of Japan, 2014. 83(2): p. 024801.
 Jiang, W., et al., Generalized scalable multiple copy algorithms for molecular dynamics simulations in NAMD. Computer physics communications, 2014. 185(3): p. 908-916.
 Rapaport, D.C., The art of molecular dynamics simulation. 2004: Cambridge university press.
 Klauda, J.B., et al., Improving the CHARMM force field for polyunsaturated fatty acid chains. The Journal of Physical Chemistry B, 2012. 116(31): p. 9424-9431.
 Mitra, A. and D. Sept, Taxol allosterically alters the dynamics of the tubulin dimer and increases the flexibility of microtubules. Biophysical journal, 2008. 95(7): p. 3252-3258.
 Phillips, J.C., et al., Scalable molecular dynamics with NAMD. Journal of computational chemistry, 2005. 26(16): p. 1781-1802.
 Frenkel, D. and B. Smit, Understanding molecular simulation: from algorithms to applications. Computational sciences series, 2002. 1: p. 1-638.
 Schreiner, W., et al., Relaxation Estimation of RMSD in Molecular Dynamics Immunosimulations. Computational and mathematical methods in medicine, 2012. 2012.
 Schieborr, U., et al., MOTOR: Model assisted software for NMR structure determination. Proteins: Structure, Function, and Bioinformatics, 2013. 81(11): p. 2007-2022.
 He, X., et al., Molecular analysis of interactions between a PAMAM dendrimer–paclitaxel conjugate and a biomembrane. Physical Chemistry Chemical Physics, 2015. 17(44): p. 29507-29517.
 Lin, X., et al., Promote potential applications of nanoparticles as respiratory drug carrier: insights from molecular dynamics simulations. Nanoscale, 2014. 6(5): p. 2759-2767.
 Mousavi, S.Z., et al., Carbon nanotube-encapsulated drug penetration through the cell membrane: an investigation based on steered molecular dynamics simulation. The Journal of membrane biology, 2013. 246(9): p. 697-704.
 Bunker, A., Poly (ethylene glycol) in drug delivery, why does it work, and can we do better? All atom molecular dynamics simulation provides some answers. Physics Procedia, 2012. 34: p. 24-33.