Nanoparticle Shape Improves Delivery: Rational Coarse Grain Molecular Dynamics (rCG-MD) of Taxol in Worm-Like PEG-PCL Micelles

Chemical and Biomolecular Engineering, University of Pennsylvania, 129 Towne Building, 220 South 33rd St., University of Pennsylvania, Philadelphia, PA 19104, USA.
Advanced Materials (Impact Factor: 17.49). 07/2012; 24(28):3823-30. DOI: 10.1002/adma.201103192
Source: PubMed


Nanoparticle shape can improve drug delivery based on the surprising effectiveness of flexible, worm-like nanocarriers (Worms) that increase the amount of drug delivered to tumors and shrink the tumors more effectively than spherical micelles (Spheres). Here, all-atom molecular dynamics (MD) simulations are used to build a rational coarse grain (rCG) model that helps clarify shape-dependent effects in delivery of the widely used anti-cancer drug Taxol by block copolymer micelles.

Download full-text


Available from: Sharon M. Loverde
  • Source
    • "The shape of the polymer is changed from spherical to almost cylindrical 4.8e. The number of attached atoms are also more in this case due to change in the shape of the polymers as rod type shape has higher adhesive probability than spherical shape[24].The external electric field with E amp = 9 Volts/Å has more effect on the polymeric shape as is visible in 4.8h. The polymers are converted into single chain structure and number of attached polymers are more then the previous case. "
    [Show abstract] [Hide abstract]
    ABSTRACT: In recent past powerful drugs are engineered to cure many diseases but they remain ineffective in targeting the infected cell. There is a large amount of research going on to improve the targeted delivery system. The attachment of nano carriers on receptors is an important stage for such applications. To carry out this investigation we used molecular dynamics (MD) model with the Pluronic copolymer L61 as nano carrier. We also investigated the impact of external oscillatory electric field on adhesion. MD is a computational technique to simulate systems from an atomic point of view. The atomistic model of polymer and water are prepared separately using XenoView molecular simulator and combined together by Moltemplate. The simulation is performed using LAMMPS molecular dynamics simulator with the help of input script and data file obtained by moltemplate. Since the polymer is amphiphilic, the self assembly of it in water is studied without any external force. After the assembly, a force is applied to all water molecules in the flow direction. The interactions between polymeric atoms and receptor is studied and reported. The density, temperature and velocity profiles are checked to confirm the stability of the simulation. The system is run in the NVT ensemble to ensure that the temperature is constant. Adhesion of polymeric atoms on receptors are visualized and quantified with respect to time. The pattern of attached atoms is compared with previously published data. Radial distribution function and mean square displacement are presented to further analyse the results. This adhesive process is also investigated in presence of oscillating electric fields and its impact is studied. It is observed that number of attached atoms saturate after some time. The external electric field helps in stretching the polymer and provide extra movement in the lateral direction which improves the adhesion significantly.
    Full-text · Thesis · Sep 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The design of nanoparticle (NP) size, shape and surface chemistry has a significant impact on their performance. While the influences of the particle size and surface chemistry on drug delivery have been studied extensively, little is known about the effect of particle shapes on nanomedicine. In this perspective article, we discuss recent progress on the design and fabrication of NPs of various shapes and their unique delivery properties. The shapes of these drug carriers play an important role in therapeutic delivery processes, such as particle adhesion, distribution and cell internalization. We envision that stimuli-responsive NPs, which actively change their shapes and other properties, might pave way to the next generation of nanomedicine.
    Full-text · Article · Feb 2012 · Therapeutic delivery
  • [Show abstract] [Hide abstract]
    ABSTRACT: Coarse-grained (CG) molecular models are now widely used to understand the structure and functionality of macromolecular self-assembling systems. In the last few years, significant efforts have been devoted to construct quantitative CG models based on data from molecular dynamics (MD) simulations with more detailed all-atom (AA) intermolecular force fields as well as experimental thermodynamic data. We review some of the recent progress pertaining to the MD simulation of self-assembling macromolecular systems, using as illustrations the application of CG models to probe surfactant and lipid self-assembly including liposome and dendrimersome formation as well as the interaction of biomembranes with nanoparticles.
    No preview · Article · Mar 2012 · Current Opinion in Structural Biology
Show more