Design of block-copolymer-based micelles for active and passive targeting

Lebouille, Jérôme G J L; Leermakers, Fam Frans; Stuart, MA Martien Cohen; Tuinier, Remco

doi:10.1103/physreve.94.042503

Cited by 4 publications

(2 citation statements)

References 38 publications

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“…For details about this procedure we refer to previous literature. 26,28,55 The preferred geometry is the one associated with the lowest f bulk value, since the free energy of micelle formation DG mic is related with f bulk via the relation DG mic ¼ k B T ln f bulk . 56 The results indicate that at neutral pH and at room temperature PMEEECL 20 -PAE M block copolymers in water assemble into spherical micelles for M # 6, into cylindrical micelles for 7 # M # 12 and into vesicles or at bilayers for M $ 13.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2020

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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 poly{g-2-[2-(2-methoxyethoxy)ethoxy]ethoxy-3-caprolactone} (PMEEECL) and poly(b-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 MEEECL 20 -AE M compositions with M ¼ 5, 10, and 15, have been studied. Allatom 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. † Electronic supplementary information (ESI) available: Computer simulations (Table S1), Flory-Huggins interaction parameters (Table S2), radii of gyration of PMEEECL and PAE parts of block copolymer (Table S3), the hydrophilic mass fraction dependency of coil-to-globule transition temperature of PMEEECL in block copolymers (Table S4), the bond and angle distribution of PMEEECL, PAE (Fig. S1), and DOX (Fig. S2), the simulation time-dependency of micelle order parameter (Fig. S3), solvent access surface area as a function of interaction energy for both PMEEECL and PAE blocks (Fig. S4), the RDF of PMEEECL block and water molecules (Fig. S5), the RDF of PAE block and water molecules (Fig. S6), the number of cluster for spherical micelles as a function of simulation time (Fig. S7), and the RDF of PMEEECL beads and water beads as a function of temperature (Fig. S8). Additionally, see Videos S1-S3 which show the encapsulation process of DOX into spherical micelle composed of PMEEECL 20 -PAE 5 when it was fed as the ratio of 1 wt%, 5 wt%, and 10 wt% to block copolymers. See Fig. 3 Snapshot series from micellization of PMEEECL 20 -PAE M with M ¼ 5, 10, and 15. Water beads are removed for clarity and blue and red beads show PMEEECL and PAE beads, respectively. This journal isFig. 5 SCF results (data) for the pH dependency of (a) the critical aggregation concentration f bulk and (b-d) the aggregation number g of the self-assembled structures of PMEEECL 20 -PAE M block copolymer with M ¼ 5, 10, and 15 in water.This journal is Fig. 6 Radial conc...

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Section: Resultsmentioning

confidence: 99%

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

et al. 2020

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“…2b) for this specific Pluronic surfactant. This is because the bridging attraction is so favourable that the polymers stretch, 35 reducing their configurational entropy, to adsorb at the surface of the bare particle as can be seen in the volume fraction profile of the polymer brush. It can be argued that this stretching might not occur in an experimental system since the surfactants have to cross an energy barrier to adsorb onto the surface of the second particle due to the stretching of the polymers to reach the thermodynamic energy minimum shown in Fig.…”

Section: Colloidal Interactionsmentioning

confidence: 99%