Jiaping Lin

Dual-drug delivery system based on hydrogel/micelle composites

We present a dual-drug delivery system (DDDS) of hydrogel/polypeptide micelle composites in this work. The DDDS was constructed from aspirin (Asp) dispersed poly(vinyl alcohol) (PVA) or Chitosan (CS)/PVA hydrogel and doxorubicin (DOX) loaded poly(L-glutamic acid)-b-poly(propylene oxide)-b-poly(L-glutamic acid) (GPG) micelles. Independent release behaviors of the two drugs are observed. Asp has a short-term release while DOX has a long-term and sustained release behavior in all the DDDSs. The release of DOX from all the DDDSs is environmentally controlled due to the pH and temperature sensitivity of the GPG micelle. Asp shows the pH controlled release behavior in CS/PVA/micelle DDDS due to the pH sensitivity of CS hydrogel. The releasing profiles were analyzed using a power law equation proposed by Peppas. It reveals that the release of Asp is anomalous transport in all the hydrogel/micelle DDDSs. The release of DOX is Fickian type in PVA/micelle system, and changes to anomalous transport in CS/PVA/micelle system according to the release exponent n.

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.

Structural Evolution of Multicompartment Micelles Self-Assembled from Linear ABC Triblock Copolymer in Selective Solvents

Using dissipative particle dynamics simulation, structural evolution from concentric multicompartment micelles to raspberry-like multicompartment micelles self-assembled from linear ABC triblock copolymers in selective solvents was investigated. The structural transformation from concentric micelles to raspberry-like micelles can be controlled by changing either the length of B blocks or the solubility of B block. It was found that the structures with B bumps on C surface (B-bump-C) are formed at shorter B block length and the structures with C bumps on B surface (C-bump-B) are formed at relative lower solubility of B blocks. The formation of B-bump-C is entropy-driven, while the formation of C-bump-B is enthalpy-dominated. Furthermore, when the length of C blocks is much lower than that of B blocks, an inner-penetrating vesicle was discovered. The results gained through the simulations provide an insight into the mechanism behind the formation of raspberry-like micelles.

Simulation‐Assisted Self‐Assembly of Multicomponent Polymers into Hierarchical Assemblies with Varied Morphologies

As you like it: The synthesis of supramolecular hierarchical nanostructures with designed morphologies has been realized through computer-simulation-guided multicomponent assembly of polypeptide-based block copolymers and homopolymers. By adjusting the attraction between hydrophobic polypeptide rods, as well as other parameters such as the molar ratio of copolymers and the rigidity of polymers, a variety of morphologies were obtained.

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.

The pH-controlled dual-drug release from mesoporous bioactive glass/polypeptide graft copolymer nanomicelle composites.

Dual-drug delivery systems are investigated for combined therapy with drugs having distinct therapeutic effects. However, the majority of current dual-drug delivery systems are designed for simultaneous release of two different drugs; the release of each individual drug cannot be controlled. In this study, we have demonstrated a novel dual-drug delivery system based on mesoporous bioactive glass/polypeptide graft copolymer nanomicelle composites. Water-soluble gentamicin and fat-soluble naproxen were used as model drugs in the study of this system. A pH-controlled release of individual drugs was achieved by the predominant release of gentamicin from mesoporous bioactive glass in an acid environment and fast release of naproxen in an alkaline environment from polypeptide nanomicelles. Our results suggest that the mesoporous bioactive glass/PBLG-g-PEG nanomicelle composites can be used as a dual-drug delivery system, and that the individual drug release can be controlled by the pH of the surrounding environment.

Discovering multicore micelles: insights into the self-assembly of linear ABC terpolymers in midblock-selective solvents

Using self-consistent field calculations, multicore micelles, such as the double-stranded superhelix, were discovered from the solution-state self-assembly of linear ABC terpolymers consisting of a solvophilic midblock and two mutually incompatible solvophobic endblocks. The multicore micelles were formed when the A and C endblocks self-associated into multiple incompatible solvophobic cores that were subdivided alternately by solvophilic B domains, thereby constructing hierarchical packing. The structures emerged depended on the relative lengths of the blocks and the solubility of the midblocks. According to the calculation results, diagrams of the observed structures as a function of the block length and midblock solubility were constructed. The results obtained can enrich our existing knowledge of the hierarchical assembly of copolymers and provide useful information for mimicking complex biological systems.

Self-assembly and photo-responsive behavior of novel ABC2-type block copolymers containing azobenzene moieties

The self-assembly behavior and photo-responsive properties of novel azobenzene based copolymers poly(ethylene oxide) monomethyl ether-block-polystyrene-block-{poly[6-(4-methoxy-azobenzene-4′-oxy) hexylmethacrylate]}2 [MPEO-b-PS-b-(PMMAZO)2] with various block lengths of PMMAZO segments in aqueous media were studied by means of transmission electron microscopy (TEM), scanning electron microscopy (SEM), laser light scattering (LLS) and UV-Vis spectrophotometry. It was found that the critical water content for the aggregate formation increases with the PMMAZO weight fraction. By tailoring the molecular structure and copolymer concentration, various self-assembled aggregates were obtained. At a lower concentration, all the copolymers self-assembled into simple vesicles. With increasing the polymer concentration, large compound vesicles were formed. The photo-sensitive properties of the formed aggregates were also studied. Upon irradiation with a polarized light, the aggregates were elongated. Large compound vesicles were found to deform into compact spindles with a very large axial ratio.

Conformational changes coupled with the isotropic-anisotropic transition. Part 1. Experimental phenomena and theoretical considerations

Abstract Phase behavior and conformation characteristics were reported for poly(γ-benzyl- l -glutamate) (PBLG) in dichloroacetic acid (DCA) and a mixed solvent of CHCl3/trifluoroacetic acid (TFA). The anisotropic–isotropic transition, where intramolecular helix–coil transition was coupled, was observed for the PBLG liquid crystal solution prepared, at room temperature, with either a decrease in temperature or an increase in acid content. The information on PBLG molecular conformation provided by IR determinations indicates that in the acid mediated liquid crystal solution, the PBLG side chain may become flexible while the helix backbone remains stable prior to the helix–coil transition. Based on the molecular information gained through the experiments, the reentrant theory previously derived (Lin J. Polymer 1997;38:4837; Lin J. Polymer 1998;39:5495) was further generalized by introducing a temperature-dependent axial ratio of the Kuhn chain. The calculations carried out show an appreciable improvement in the agreement between the theory and the experimental phase diagram. The present theory also accounts, reasonably, for the temperature dependence of the PBLG order parameter observed in the experiments.