Compound Vesicles Research Articles

Dendritic poly(benzyl ether)‐b‐poly(N‐vinylcaprolactam) block copolymers: Self‐organization in aqueous media, thermoresponsiveness and biocompatibility

ABSTRACTFour generations of new amphiphilic thermoresponsive linear‐dendritic block copolymers (LDBCs) with a linear poly(N‐vinylcaprolactam) (PNVCL) block and a dendritic poly(benzyl ether) block are synthesized by atom transfer radical polymerization (ATRP) of N‐vinylcaprolactam (NVCL) using dendritic poly(benzyl ether) chlorides as initiators. The copolymers have been characterized by 1H NMR, FTIR, and GPC showing controlled molecular weight and narrow molecular weight distribution (PDI ≤ 1.25). Their self‐organization in aqueous media and thermoresponsive property are highly dependent on the generation of dendritic poly(benzyl ether) block. It is observed for the LDBCs that the self‐assembled morphology changes from irregularly spherical micelles, vesicles, rod‐like large compound vesicles (LCVs), to the coexistence of spherical micelles and rod‐like LCVs, as the generation of the dendritic poly(benzyl ether) increases. The results of a cytotoxicity study using an MTT assay method with L929 cells show that the LDBCs are biocompatible. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 300–308

Electrohydrodynamics of a compound vesicle under an AC electric field

Compound vesicles are relevant as simplified models for biological cells as well as in technological applications such as drug delivery. Characterization of these compound vesicles, especially the inner vesicle, remains a challenge. Similarly their response to electric field assumes importance in light of biomedical applications such as electroporation. Fields lower than that required for electroporation cause electrodeformation in vesicles and can be used to characterize their mechanical and electrical properties. A theoretical analysis of the electrohydrodynamics of a compound vesicle with outer vesicle of radius Ro and an inner vesicle of radius , is presented. A phase diagram for the compound vesicle is presented and elucidated using detailed plots of electric fields, free charges and electric stresses. The electrohydrodynamics of the outer vesicle in a compound vesicle shows a prolate-sphere and prolate-oblate-sphere shape transitions when the conductivity of the annular fluid is greater than the outer fluid, and vice-versa respectively, akin to single vesicle electrohydrodynamics reported in the literature. The inner vesicle in contrast shows sphere-prolate-sphere and sphere-prolate-oblate-sphere transitions when the inner fluid conductivity is greater and smaller than the annular fluid, respectively. Equations and methodology are provided to determine the bending modulus and capacitance of the outer as well as the inner membrane, thereby providing an easy way to characterize compound vesicles and possibly biological cells.

Biocompatible Soft Nanoparticles with Multiple Morphologies Obtained from Nanoprecipitation of Amphiphilic Graft Copolymers in a Backbone-Selective Solvent

Stealth nanocarriers are a promising technology for the treatment of diseases. However, the preparation and characterization of well-defined soft nanoparticulate systems remain challenging. Here we describe a platform of amphiphilic graft copolymers leading to nanoparticles with multiple morphologies and the role of the hydrophilic backbone in their interaction with a model protein. The amphiphilic graft copolymers platform was composed of hydrophilic backbone poly(2-methyl-2-oxazoline-co-2-pentyl-2-oxazoline) (P(MeOx-co-PentOx)), prepared via cationic ring-opening polymerization. Hydrophobic poly(d,l-lactide) (PLA) chains were grafted on the backbone via Huisgen 1,3-dipolar cycloaddition. The "click" copper-catalyzed cycloaddition reactions of azides with alkynes (CuAAC) were successfully carried out, and a series of amphiphilic copolymers were prepared containing a backbone with a number-average molecular weight of 14.2 × 103 g mol-1 and different hydrophobic PLA grafts with various molecular weights (2.8 × 103-12.4 × 103 g mol-1). These original architectures of copolymers, when nanoprecipitated in water, the backbone-selective solvent, allowed us to obtain various structures of nanoparticles with a hydrodynamic diameter in the range of 65-99 nm. More interestingly, a plurality of morphologies going from unilamellar, multilamellar, and large compound vesicles to core-shell nanoparticles and depending on the PLA molecular weights were evidenced by combining cryo-transmission electron microscopy (cryo-TEM) and small-angle neutron scattering (SANS) studies. A first evaluation of their stealthiness by studying the stability and the interaction of these nano-objects with a model protein revealed the role played by the P(MeOx-co-PentOx) in these interactions, demonstrating the utility of this amphiphilic graft copolymers platform with well-defined architectures for the design of nanocarriers in drug delivery applications.

Adding a solvophilic comonomer to the polymerization-induced self-assembly of block copolymer and homopolymer: a cooperative strategy for preparing large compound vesicles

We report a RAFT dispersion polymerization of styrene and 4-vinylpyridine in methanol/water at 70 °C. The polymerization was mediated by a binary mixture of DDMAT and mPEG45-DDMAT.

Surface functionalized nano‐objects from oleic acid‐derived stabilizer via non‐polar RAFT dispersion polymerization

ABSTRACTSurface functionalization in a nanoscopic scaffold is highly desirable to afford nano‐particles with diversified features and functions. Herein are reported the surface decoration of dispersed block copolymer nano‐objects. First, side‐chain double bond containing oleic acid based macro chain transfer agent (macroCTA), poly(2‐(methacryloyloxy)ethyl oleate) (PMAEO), was synthesized by reversible addition‐fragmentation chain transfer (RAFT) polymerization and used as a steric stabilizer during the RAFT dispersion block copolymerization of benzyl methacrylate (BzMA) in n‐heptane at 70 °C. We have found that block copolymer morphologies could evolve from spherical micelles, through worm to vesicles, and finally to large compound vesicles with the increase of solvophobic poly(BzMA) block length, keeping solvophilic chain length and total solid content constant. Finally, different thiol compounds having alkyl, carboxyl, hydroxyl, and protected amine functionalities have been ligated onto the PMAEO segment, which is prone to functionalization via its reactive double bond through thiol‐ene radical reactions. Thiol‐ene modification reactions of the as‐synthesized nano‐objects retain their morphologies as visualized by field emission‐scanning electron microscopy. Thus, the facile and modular synthetic approach presented in this study allowed in situ preparation of surface modified block copolymer nano‐objects at very high concentration, where renewable resource derived oleate surface in the nanoparticle was functionalized. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 263–273

Self-Assembly of Polyurethane Phosphate Ester with Phospholipid-Like Structures: Spherical, Worm-Like Micelles, Vesicles, and Large Compound Vesicles.

Here, we report the preparation and self-assembly of amphiphilic polyurethane phosphate ester (PUP) polymers with phospholipid-like structures. The polymers, designed to have a hydrophilic phosphate head and two amphiphilic PPG-IPDI-MPEG (PU) tails were synthesized via coupling and phosphorylation reactions in sequence. These amphiphilic polymers could self-assemble into various interesting nanostructures in aqueous solution, such as spherical, worm-like micelles, vesicles, and large compound vesicles, depending on the hydrophobic chain length of PU tails and the initial polymer concentrations. It was found that the morphology transition is not only caused by the unique molecular structure of amphiphilic polyurethanes, but also influenced by the additional hydrophilic phosphate groups incorporated, which disturb the force balance governing the aggregation structures. This research supplies a new clue for the fabrication of well-defined nanostructures.

Temperature‐Induced Transformation from Large Compound Vesicles to Worm‐like Aggregates by ABC Triblock Copolymer

AbstractTwo triblock polymers, tetraaniline‐block‐poly(N‐isopropyl acrylamide)‐block‐poly(hydroxyethyl acrylate) (TA‐b‐PNIPAM‐b‐PHEA) and TA‐b‐PHEA‐b‐PNIPAM, were synthesized with unambiguous structure by a two step method. The difference of these two diblock polymers is the connection order of carboxyl group to block, e.g., carboxyl group to PNIPAM block for PNIPAM‐b‐PHEA and to PHEA block for PHEA‐b‐PNIPAM. Secondly, block tetraaniline was linked to the diblock polymer through amidation to yield the corresponding triblock copolymer. Both of them have almost the identical chemical compositions. The only difference is the connection order of each block in the triblock polymers. When they were self‐assembled at 45°C in a suitable solution, both of their aggregates have spherical shape with slight defects on their surface with the average diameter of about 400 nm. However, when their aggregate dispersion was cooled down to 20°C, only TA‐b‐PHEA‐b‐PNIPAM's morphology changed, forming worm‐like aggregates with the diameter of about 100–200 nm transformed from spherical aggregates. Both amphiphilic property and position of each block in this triblock copolymer are very essential for this morphology transformation. Since the worm‐like aggregates presented here by our group have hollow structure inside, its controlled release properties for doxorubicin were evaluated. Drug release experiment indicated that along with the temperature changes, the rearrangement of the intermediate layer structure caused morphology change in aggregate, thus accelerating the speed of drug release.

Formation of Hexagonally Packed Hollow Hoops and Morphology Transition in RAFT Ethanol Dispersion Polymerization.

Similar to the traditional self-assembly strategy, polymerization induced self-assembly and reorganization (PISR) can produce a myriad of polymeric morphologies through morphology transitions. Besides the chain length ratio (R) of the hydrophobic to the hydrophilic blocks, the chain mobility in the intermediate nano-objects, which is a requisite for morphology transition, is a determining factor in the formation of the final morphology. Although various morphologies have been fabricated, hexagonally packed hollow hoops (HHHs) with highly ordered internal structure have not, to the best of our knowledge, been prepared by PISR. In this article, the fabrication of HHHs through morphology transition from large compound vesicles to HHHs is reported. HHHs with highly regular internal structure may have significance in theoretical research and practical applications of nanomaterials.

Synthesis of star poly(N-isopropylacrylamide) with a core of cucurbit[6]uril via ATRP and controlled thermoresponsivity.

A series of CB[6]-based macroinitiators with "n" bromo-initiation sites on the "equator" of CB[6] is developed for the synthesis of CB[6]-star poly(N-isopropylacrylamide) (CB[6]-star PNIPAM) by atom transfer radical polymerization. By taking advantage of the exceptional binding affinity of the CB[6] core, CB[6]-star PNIPAM is used as a host macromolecule to construct large compound vesicles in the presence of protonated n-butylamine at pH 5.63. The deprotonated n-butylamine is detached from the CB[6] core at pH 11.1, which destructs the vesicular structures. For CB[6]-star PNIPAM, the thermoresponsive properties can be adjusted by simply changing the formation and destruction of the inclusion complexes of the CB[6] core with n-butylamine. These results suggest that the prepared CB[6]-star PNIPAM shows pH and temperature responsiveness, which has great potential for the design of a dual response smart material.

Large compound vesicles from amphiphilic block copolymer/rigid-rod conjugated polymer complexes.

Morphology evolution in complexes of amphiphilic block copolymers poly(styrene)-b-poly(acrylic acid) (PS-b-PAA) and poly(styrene)-b-poly(ethylene oxide) (PS-b-PEO) in the presence of polyaniline (PANI) in aqueous solution is reported. Transmission electron microscopy, atomic force microscopy, and dynamic light scattering techniques were used to study the morphologies at various PANI contents [aniline]/[acrylic acid] ([ANI]/[AA]) ranging from 0.1 to 0.7. The interpolyelectrolyte complex formed between PAA and PANI plays a key role in the morphology transformation. Spherical micelles formed from pure block copolymers were transformed into large compound vesicles upon increasing PANI concentration due to internal block copolymer segregation. In addition to varying PANI content, the kinetic pathway of nanoparticle formation was controlled through different water addition methods and was critical in the formation of multigeometry nanoparticles.

An Unconditionally Energy Stable Penalty Immersed Boundary Method for Simulating the Dynamics of an Inextensible Interface Interacting with a Solid Particle

In this paper, a novel penalty method based on the immersed boundary formulation is proposed for simulating the transient Stokes flow with an inextensible interface enclosing a suspended solid particle. The main idea of this approach relies on the penalty techniques by modifying the constitutive equation of Stokes flow to weaken the incompressibility condition, relating the surface divergence to the elastic tension $$\sigma $$? to relax the interface's inextensibility, and connecting the particle surface-velocity with the particle surface force $${\varvec{F}}$$F to regularize the particle's rigid motion. The advantage of these regularized governing equations is that when they are discretized by the standard centered difference scheme on a staggered grid, the resulting linear system can easily be reduced by eliminating the unknowns $$p_h, \sigma _h$$ph,?h and $${\varvec{F}}_h$$Fh directly, so that we just need to solve a smaller linear system of the velocity approximation $${\varvec{u}}_h$$uh. This advantage is preserved and even enhanced when such approach is applied to the transient Stokes flow with multiple compound vesicles. Moreover, this smaller linear system is symmetric and negative-definite, which enables us to use efficient linear solvers. Another important feature of the proposed method is that the discretization scheme is unconditionally stable in the sense that an appropriately defined energy functional associated with the discrete system is decreasing and hence bounded in time. We numerically test the accuracy and stability of the immersed boundary discretization scheme. The tank-treading and tumbling motions of inextensible interface with a suspended solid particle in the simple shear flow will be studied extensively. The simulation of the motion of multiple compound vesicles will be performed as well. Numerical results illustrate the superior performance of the proposed penalty method.

Well-defined poly(DL-lactide)-b-poly(N-vinylcaprolactam) copolymers: synthesis, solution properties and in vitro degradation

Well-defined thermoresponsive amphiphilic poly(DL-lactide)-b-poly(N- vinylcaprolactam) (PDLLA-b-PNVCL) block copolymers with various block compositions were synthesized via a combination of ring-opening polymerization (ROP) and atom transfer radical polymerization (ATRP). Their structures were confirmed by proton nuclear magnetic resonance spectroscopy (1H NMR) and gel permeation chromatography/multi-angle laser light scattering (GPC/MALLS) measurements. They exhibited reversible temperature-dependent aggregation behavior in aqueous media as characterized by turbidity and dynamic light scattering (DLS) measurements. Their lower critical solution temperatures (LCSTs) increased with the increase in the chain length of PNVCL block and the decrease of the copolymer solution concentrations. These amphiphilic block copolymers self-assembled into aggregates of various morphologies in their aqueous solution, depending on the compositions of the copolymers. As the PNVCL content in block copolymer increased, the morphology of the aggregates changed from spheres to large compound vesicles (LCVs)-like, to irregularly spherical micelles. The viscosity measurement and 1HNMR analyses proved that these copolymers were hydrolytically degradable and the degradation process was accelerated under basic and acidic environments, especially in acidic media.

Biodegradable large compound vesicles with controlled size prepared via the self-assembly of branched polymers in nanodroplet templates.

Generally, it is very difficult to control the size of large compound vesicles. Here, we introduce a novel method for the preparation of biodegradable large compound vesicles with controlled size and narrow size distribution by using aqueous nanodroplets as templates.

Synthesis and self-assembly of stimuli-responsive amphiphilic block copolymers based on polyhedral oligomeric silsesquioxane

A novel POSS-containing methacrylate monomer (HEMAPOSS) was fabricated by extending the side chain between polyhedral oligomeric silsesquioxane (POSS) unit and methacrylate group, which can efficiently decrease the steric hindrance in free-radical polymerization of POSS-methacrylate monomer. POSS-containing homopolymers (PHEMAPOSS) with a higher degree of polymerization (DP) can be prepared using HEMAPOSS monomer via reversible addition–fragmentation chain transfer (RAFT) polymerization. PHEMAPOSS was further used as the macro-RAFT agent to construct a series of amphiphilic POSS-containing poly(N, N-dimethylaminoethyl methacrylate) diblock copolymers, PHEMAPOSS-b-PDMAEMA. PHEMAPOSS-b-PDMAEMA block copolymers can self-assemble into a plethora of morphologies ranging from irregular assembled aggregates to core-shell spheres and further from complex spheres (pearl-necklace-liked structure) to large compound vesicles. The thermo- and pH-responsive behaviors of the micelles were also investigated by dynamic laser scattering, UV spectroscopy, SEM, and TEM. The results reveal the reversible transition of the assembled morphologies from spherical micelles to complex micelles was realized through acid-base control. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 2669-2683

CBABC terpolymer-based nanostructured vesicles with tunable membrane permeability as potential hydrophilic drug nanocarriers

The self-assembly of an amphiphilic pentablock terpolymer, consisting of a pH-sensitive poly(2-vinylpyridine) (P2VP) central block, bearing at both ends hydrophilic poly(ethylene oxide) (PEO) end-capped with hydrophobic poly(ε-caprolactone) (PCL) blocks was investigated in aqueous media. When the polymer was transferred to aqueous medium through solvent exchange technique, micellar assemblies were obtained, with a morphological switch from “flower-like” crew-cut micelles to large compound vesicles upon partial quaternization of 2VP block. More importantly, well-defined polymer vesicles were formed when thin film hydration method was employed. Such polymersomes presented “flower-like” morphology, with a membrane composed of self-assembled P2VP hydrophobic central blocks shielded by PCL hydrophobic ends and surrounded by PEO looping chains at the inner and outer surfaces. The potential of the pentablock vesicles as drug delivery carriers was explored by encapsulation of calcein, a model hydrophilic drug, in the polymersomes and monitoring its release at different pH values simulating physiological environments. It is shown that the release profile of the nanoparticle formulations could be modulated by tuning the membrane permeability either through chemical (i.e. partial quaternization) and/or physical (i.e. pH variations) pathways.

Complex dynamics of compound vesicles in linear flow.

We report first experimental observations of dynamics of compound vesicles in linear flow realized in a microfluidic four-roll mill. We show that while a compound vesicle undergoes the same main tank-treading, trembling (TR), and tumbling regimes, its dynamics are far richer and more complex than that of unilamellar vesicles. A new swinging motion of the inner vesicle is found in TR in accord with simulations. The inner and outer vesicles can exist simultaneously in different dynamical regimes and can undergo either synchronized or unsynchronized motions depending on the filling factor. A compound vesicle can be used as a physical model to study white blood cell dynamics in flow similar to a unilamellar vesicle used successfully to model anucleate cells.

New Strategy for Controlled Release of Drugs. Potential Pinpoint Targeting with Multiresponsive Tetraaniline Diblock Polymer Vesicles: Site-Directed Burst Release with Voltage

A series of amphiphlic diblock polymers, tetraaniline block with different length of poly(N-isopropylacrylamide) (TA-b-PNIPAM), have been successfully synthesized. In a suitable solution, the as-synthesized diblock polymers can form stable large compound vesicles (LCVs) with multiple bimolecular-layer structure through self-assembly. These factors, such as the block length, different organic solvent, solvent ratio, pH value, temperature, and voltage, which affect the morphology and properties of the assembled aggregates, are systematically investigated. When the degree of polymerization of PNIPAM block is close to 10, the as-synthesized diblock polymer may form stable LCVs with the uniform size as well as few defects in the mixed solvent of dimethylformamide/water (v/v = 3:7). The assembled LCVs possess the properties of triple-responsive capacity on temperature, pH, and voltage. Variation in any of these factors can cause some changes in the morphology of LCVs. The drug release properties for doxorubicin (DOX) loaded by LCVs affected by temperature, voltage, and different pH values have been investigated. It is interesting that the structure of LCVs can be destructed completely by applying a voltage at 0.6 V. With such an advantage, the drugs loaded by the LCVs could burst release into designated place by using appropriate circuit design or instrument, thus achieving maximum efficacy of the loaded drugs or other bioactive molecules without any unnecessary chemical substances added. This approach allows us to concentrate more on material design aspects only, without regard to the complex targeting issue which is the biggest obstacle of such materials in practical applications.

New Morphologies and Phase Transitions of Rod–Coil Dendritic–Linear Block Copolymers Depending on Dendron Generation and Preparation Procedure

Amphiphilic rod–coil dendritic–linear block copolymers PEG(Gm)-b-PMPCS (where m is the number of dendron generation, and m = 1, 2, 3) composed of a semirigid Percec-type dendron with hydrophilic poly(ethylene glycol) (PEG) tails and a rod-like mesogen-jacketed liquid crystalline polymer, poly{2,5-bis[(4′-methoxy-phenyl)oxycarbonyl]styrene} (PMPCS), were successfully prepared. The self-assembled structures undergo a transition from vesicles through large compound vesicles (LCVs) to short cylindrical micelles with increasing dendron generation. PEG(G2)-b-PMPCS forms stable LCVs with porous surfaces of a narrow size distribution in a mixed solvent of tetrahydrofuran and water. The formation mechanism of the supramolecular structure with nano- and microsized scales is studied through changing the rate of water addition. It is composed of two steps: morphological transformation and vesicles fusion or differentiation. Vesicles are precursors for LCVs regardless of what the initial morphology is. However, the fi...

Controlled self-assembly of amphiphilic monotailed single-chain nanoparticles

In the field of materials science, one of the current challenges is to organize nanoparticles with various sizes, geometries and compositions into specific structures for constructing functional materials and devices. In this research, the self-assembly of the monotailed single-chain nanoparticles with different charge densities was investigated. Poly(2-(dimethylamino)ethyl methacrylate)-block-polystyrene (PDMAEMA-b-PS) was synthesized by reversible addition–fragmentation chain transfer polymerization, and amphiphilic monotailed PDMAEMA single-chain nanoparticles were prepared by intramolecular cross-linking of PDMAEMA blocks. The cross-linking degree was controlled at about 20%. The surface charge densities on the single-chain nanoparticles were controlled by reactions of the single-chain nanoparticles with varying amounts of iodomethane. The surface charge density has a significant influence on the self-assembly of the monotailed single-chain nanoparticles. The monotailed single-chain nanoparticles made from PDMAEMA74-b-PS100 self-assemble into spherical micelles in aqueous solutions, and the average size of the micelles increases with the charge density. With an increase in the charge density, the morphology of the aggregates self-assembled by the monotailed single-chain nanoparticles changes from spherical micelles to vesicles, and to a mixture of worm-like cylinders and vesicles. In a cyclohexane–THF mixture, the monotailed single-chain nanoparticles made from PDMAEMA74-b-PS297 self-assemble into bunchy micelles, or a mixture of vesicles and large compound vesicles, depending on the charge densities.

Synthesis and pH-Responsive “Schizophrenic” Aggregation of a Linear-Dendron-Like Polyampholyte Based on Oppositely Charged Polypeptides

A novel linear-dendron-like polyampholyte, poly(L-lysine)-b-D2-poly(L-glutamic acid) [PLL-b-D2-(PLGA)4], where D2 is the second generation of poly(amido amine), was prepared by hydrolyzing poly(ε-benzyloxycarbonyl-L-lysine)-b-D2-poly(γ-benzyl-L-glutamate) copolymer which was synthesized via a combination of ring-opening polymerization and click chemistry. The pH-responsive self-assembly behaviors of PLL-b-D2-(PLGA)4 were investigated in detail. It is found that PLL-b-D2-(PLGA)4 can self-assemble into PLGA-core aggregates at acidic pH and PLL-core aggregates at alkaline pH, which was accompanied with the coil-to-helix conformational transition of PLGA and PLL segments, respectively. The self-assembled aggregates with various morphologies, such as large compound micelles, worm-like micelles, large compound vesicles, simple vesicles, and rigid tubular structures have been obtained in "schizophrenic" aggregation process with simply increasing the solution pH. The hierarchical assembled fractal structures of PLL-b-D2-(PLGA)4 were observed during the solvent evaporation at high pH value.