Dual responsive PMEEECL-PAE block copolymers: a computational self- assembly and doxorubicin uptake study

A Koochaki and MR Moghbeli and SJ Nikkhah and A Ianiro and R Tuinier, RSC ADVANCES, 10, 3233-3245 (2020).

DOI: 10.1039/c9ra09066e

The self-assembly behaviour of dual-responsive block copolymers and their ability to solubilize the anticancer drug doxorubicin (DOX) has been investigated using all-atom molecular dynamics (MD) simulations, MARTINI coarse-grained (CG) force field simulation and Scheutjens-Fleer self-consistent field (SCF) computations. These diblock copolymers, composed of polygamma-2-2-(2-methoxyethoxy)ethoxyethoxy-epsilon- caprolactone (PMEEECL) and poly(beta-amino ester) (PAE) are dual- responsive: the PMEEECL block is thermoresponsive (becomes insoluble above a certain temperature), while the PAE block is pH-responsive (becomes soluble below a certain pH). Three MEEECL20-AE(M) compositions with M = 5, 10, and 15, have been studied. All-atom MD simulations have been performed to calculate the coil-to-globule transition temperature (T-cg) of these copolymers and finding appropriate CG mapping for both PMEEECL-PAE and DOX. The output of the MARTINI CG simulations is in agreement with SCF predictions. The results show that DOX is solubilized with high efficiency (75-80%) at different concentrations inside the PMEEECL-PAE micelles, although, interestingly, the loading efficiency is reduced by increasing the drug concentration. The non-bonded interaction energy and the RDF between DOX and water beads confirm this result. Finally, MD simulations and SCF computations reveal that the responsive behaviour of PMEEECL-PAE self-assembled structures take place at temperature and pH ranges appropriate for drug delivery.

Return to Publications page