(581g) A Coarse Grained Model for PCL: Conformation, Self-Assembly of Mepeg-b-PCL Amphiphilic Diblock Copolymers

We
report the development of a coarse grained molecular model within the MARTINI
framework for Polycaprolactone (PCL), a biodegradable hydrophobic polymer. PCL
is applied in drug delivery, especially in the form of self-assembled
nanoparticles. Hydrophobic drugs that cannot be directly administered into the
systemic circulation, can be encapsulated in the hydrophobic PCL core of these
self-assembled nanoparticles, thereby enabling their delivery. Computational
studies on the self-assembly of molecules involving PCL, necessitate the
development of a robust coarse grained model.

We
parametrized the intramolecular interactions in the coarse grained model by
mapping onto the OPLS-united-atom (OPLS-UA) rendition of PCL. The coarse
grained model for PCL was validated by examining the polymer chain
conformation, as well as by molecular dynamics simulations of self-assembled
micelles formed by an amphiphilic Methoxy polyethylene
glycol-(block)-Polycaprolactone (MePEG-b-PCL) linear diblock copolymer. We
compared the polymer chain conformation of the coarse-grained polymer model in
water with that of an OPLS-all atom (OPLS-AA) rendition, for different polymer
chain lengths. We found that the average end to end distance, radius of
gyration and other key properties showed excellent agreement between the coarse
grained and all atom models. We also studied the self-assembly of the amphiphilic
(MePEG₁₇-b-PCL₃) diblock copolymer system, using an
existing MARTINI coarse grained model for MePEG [1], and the model developed in
this work, for PCL. We observed a gradual self-assembly of the block copolymer
into large spherical micelles that consisted of a hydrophobic PCL core
surrounded by MePEG. We computed the aggregation number of the micelles and
their hydrodynamic radii. We also determined the critical micelle concentration
(CMC) of MePEG₁₇-b-PCL₂ diblock copolymers, which was
found in a reasonable agreement with experiment.

Fig.1.
Self-assembly of MePEG₁₇-b-PCL₃ linear diblock
copolymers. Snapshots at the initial and final simulation time. (Color codes:
MePEG-Green, PCL-Red)

[1] Hwankyu Lee, Alex H. de Vries, Siewert-Jan Marrink and Richard W. Pastor,  J. Phys. Chem. B, 2009, 113 (40), pp 13186-13194.