Liangshun Zhang

Drug releasing behavior of hybrid micelles containing polypeptide triblock copolymer

We report a new type of hybrid polymeric micelles for drug delivery applications. These micelles consist of PLGA (PLGA: poly(l-glutamic acid)) and PEG (PEG: polyethylene glycol) mixed corona chains. In acidic condition, PLGA undergoes a transformation from water-soluble random coils to water-insoluble alpha-helix, leading to microphase separation in micelle coronas and formation of PEG channels. These channels connect the inner core and the outer milieu, accelerating the diffusion of drugs from micelles. The micelles were prepared through a co-micellization of PLGA-b-PPO-b-PLGA (PPO: poly(propylene oxide)) and PEG-b-PPO in water. During the self-assembly, the PPO blocks of both block copolymers aggregated into cores that were surrounded by mixed corona chains of PLGA and PEG blocks. We confirmed this structure by using a number of characterization techniques including nuclear magnetic resonance spectroscopy, zeta potential, circular dichroism, and dynamic light scattering. We also performed molecular dynamics (MD) simulations to verify the models of the hybrid micelle structure. One advantage of the hybrid micelles as drug carriers is their tunable release rate without sacrificing colloidal stability. The rate can be tuned by either micelle structures such as the composition of the mixture or external parameters such as pH.

Ordered Nanostructures Self-Assembled from Block Copolymer Tethered Nanoparticles

Combining the self-consistent field theory (SCFT) and the density functional theory (DFT), we investigated the self-assembly behavior of AB diblock copolymer tethered single spherical particle P (ABP molecules). Two cases were studied: one is where the particles are chemically neutral to both A and B blocks, and the other is where the particles are unfavorable to neither of the two blocks. For neutral particles, the ABP molecules self-assemble to typical equilibrium microstructures, such as lamellae and cylinders. The P particles are localized in B block domains, and the size of particles can influence the phase behavior. For unfavorable particles, the ABP molecules microphase separate to form distinct ordered structures. Hierarchical structures, such as cylinders with cylinders at the interfaces and lamellae with cylinders at the interfaces, were observed. These resulting hierarchical structures are mainly determined by two parameters: A block fraction f(A) and particle size R(P). On the basis of the calculation results, phase diagrams were constructed.

Self-assembly behavior of pH- and thermosensitive amphiphilic triblock copolymers in solution: experimental studies and self-consistent field theory simulations.

We investigated, both experimentally and theoretically, the self-assembly behaviors of pH- and thermosensitive poly(L-glutamic acid)- b-poly(propylene oxide)-b-poly(L-glutamic acid) (PLGA-b-PPO-b-PLGA) triblock copolymers in aqueous solution by means of transmission electron microscopy (TEM), scanning electron microscopy (SEM), dynamic light scattering (DLS), circular dichroism (CD), and self-consistent field theory (SCFT) simulations. Vesicles were observed when the hydrophilic PLGA block length is shorter or the pH value of solution is lower. The vesicles were found to transform to spherical micelles when the PLGA block length increases or its conformation changes from helix to coil with increasing the pH value. In addition, increasing temperature gives rise to a decrease in the size of aggregates, which is related to the dehydration of the PPO segments at higher temperatures. The SCFT simulation results show that the vesicles transform to the spherical micelles with increasing the fraction or statistical length of A block in model ABA triblock copolymer, which corresponds to the increase in the PLGA length or its conformation change from helix to coil in experiments, respectively. The SCFT calculations also provide chain distribution information in the aggregates. On the basis of both experimental and SCFT results, the mechanism of the structure change of the PLGA- b-PPO- b-PLGA aggregates was proposed.

Self-assembly behavior of AB/AC diblock copolymer mixtures in dilute solution.

The self-assembly behavior of AB/AC amphiphilic diblock copolymer mixtures in dilute solution was studied by a real-space-implemented self-consistent field theory in three dimensions. The AB and AC copolymers have a common hydrophobic block A but different hydrophilic blocks B and C. Two cases were studied: one in which copolymers AB and AC have same hydrophobic and hydrophilic block lengths and one in which copolymers AB and AC have different hydrophobic and hydrophilic block lengths. It was found that the two copolymers can cooperatively self-assemble into hybrid aggregates. The morphologies of the formed aggregates were found to be dependent on the mixture ratio and the interaction between the B and C blocks. For the AB/AC copolymers with different hydrophobic and hydrophilic lengths, chain segregation was found in the formed hybrid aggregates. Based on the obtained calculation results, phase diagrams as functions of the mixture ratio and interaction between the B and C blocks were constructed.

Hierarchically ordered microstructures self-assembled from comb-coil block copolymers.

Using the real-space implemented self-consistent field theory, we undertook an investigation on the hierarchical self-assembly behaviors of comb-coil block copolymers. The comb-coil block copolymers can self-assemble into hierarchical microstructures with two different length scales. Various structure-within-structure morphologies, such as parallel and perpendicular lamella-within-lamella, cylinder-within-lamella, lamella-within-cylinder, and cylinder-within-cylinder, were observed. In the hierarchical structures, the large-length-scale structures are produced by segregation between the coil blocks and comb blocks, and the small-length-scale structures are formed by microphase separation within the comb blocks. Effects of interaction strength and coil block length on the hierarchical phase behaviors were studied, and the phase diagram was mapped out accordingly. Furthermore, the large-length-scale lamellar period as a function of interaction strength was examined. It was found the lamellar periods are greatly dependent on interaction strengths.

Effect of Molecular Architecture on Phase Behavior of Graft Copolymers

Influence of molecular architecture on phase behavior of graft copolymer melts was studied by using a reciprocal-space self-consistent filed theory (SCFT). The phase diagrams were examined as functions of the architectural parameters describing the graft copolymers (i.e., the number of grafts and the position of first junction). In comparison with the well-known phase diagram of diblock copolymers, the phase diagrams of the graft copolymers are asymmetric. When the number of grafts or the position of first junction varies, the boundaries of order-order transitions have shifts due to the variation in the chain stretching energy. The change in molecular architecture also significantly alters the domain spacing of ordered structures but has weak impact on the density distributions of graft copolymers. For comparison of the theoretical predictions with the existing experimental results, the phase diagrams of graft copolymers were also calculated at strong segregation. The SCFT calculations can accurately capture the characteristics of the phase behavior of graft copolymer melts.

Microphase separation in multigraft copolymer melts studied by random-phase approximation and self-consistent field theory

Microphase separation of AB multigraft copolymers with various numbers of graft arms per junction along the backbone was examined by the random-phase approximation and real-space implemented self-consistent field theory. The calculations carried out show that the number of graft arms per junction exerts a marked effect on the phase behavior of the multigraft copolymers. The spinodal shows an upward shift with increasing number of graft arms per junction. The order-order transitions shift toward the higher volume fraction of backbone and the ordered region becomes narrower when the number of graft arms per junction increases. The influence of the number of graft arms per junction on the domain size and the interfacial width has also been examined. It was found that the characteristic domain size decreases and the interfacial width broadens with increasing number of graft arms per junction. The theoretical results at a strong segregation were compared with the existing experimental observations and a good agreement is shown.

Elastic properties of graft copolymers in the lamellar phase studied by self-consistent field theory

The linear elasticity of graft copolymer melts in the lamellar phase was examined by the self-consistent field theory solved in real space. The extensional and shear moduli, which are used to derive the Youngs modulus, are found to be dependent on the architecture parameters of graft copolymers (the number of branches and the distribution of junction points). Compared with the shear modulus, the extensional modulus makes a greater contribution to the Youngs modulus. The graft copolymers with the larger branch number exhibit the better mechanical properties. For the physical origin of the improvement of mechanical properties, the contribution of internal energy is the main drive, while the contribution of entropy to the moduli is negative or neglected. The distribution of junction points was also found to play a role in determining the elastic properties. These findings gained through the theoretical calculations may provide useful information for designing graft copolymers with enhanced properties.

Microphase separation of rod-coil diblock copolymer in solution

Lattice theory of rigid rods is extended to describe the microphase separation behavior of a rod-coil diblock copolymer in solution. The free energy was formulated by inclusion of the energy terms arising from the core-corona interface between the rods and coils and the corona formed by the coils into the lattice model of rigid rods. The rod-coil diblock copolymer exhibits lyotropic mesophases with lamellar, cylindrical, and spherical structures when the copolymer concentration is above a critical value. The tendency of the rodlike blocks to form orientational order plays an important role in the formation of lyotropic phases. Influences of polymer-solvent interaction, surface free energy, and molecular architectures of the rod-coil diblock copolymer on the phase behaviors were studied, and phase diagrams were mapped accordingly. The theoretical results were compared with some existing experimental observations and a good agreement is shown.

Understanding the ordering mechanisms of self-assembled nanostructures of block copolymers during zone annealing

A theoretical method based on dynamic version of self-consistent field theory is extended to investigate directed self-assembly behaviors of block copolymers subjected to zone annealing. The ordering mechanisms and orientation modulation of microphase-separated nanostructures of block copolymers are discussed in terms of sweep velocity, wall preference, and Flory-Huggins interaction parameter. The simulated results demonstrate that the long-range ordered nanopatterns are achieved by lowering the sweep velocity of zone annealing due to the incorporation of templated ordering of block copolymers. The surface enrichment by one of the two polymer species induces the orientation modulation of defect-free nanostructures through finely tuning the composition of block copolymers and the preference of walls. Additionally, the Flory-Huggins interaction parameters of block copolymers in the distinct regions are main factors to design the zone annealing process for creating the highly ordered nanostructures with single orientation.