Amphiphilic Copolymer Micelles Research Articles

Molecular Weight-Independent "Polysoap" Nanostructure Characterized via In Situ Resonant Soft X-ray Scattering.

Studying polymer micelle structure and loading dynamics under environmental conditions is critical for nanocarrier applications but challenging due to a lack of in situ nanoprobes. Here, the structure and loading of amphiphilic polyelectrolyte copolymer micelles, formed by 2-acrylamido-2-methylpropanesulfonic acid (AMPS) and n-dodecyl acrylamide (DDAM), were investigated using a multimodal approach centered around in situ resonant soft X-ray scattering (RSoXS). We observe aqueous micelles formed from polymers of wide-ranging molecular weights and aqueous concentrations. Despite no measurable critical micelle concentration (CMC), structural analyses point toward multimeric structures for most molecular weights, with the lowest molecular weight micelles containing mixed coronas and forming loose micelle clusters that enhance hydrocarbon uptake. The sizes of the micelle substructures are independent of both the concentration and molecular weight. Combining these results with a measured molecular weight-invariant surface charge and zeta potential strengthens the link between the nanoparticle size and ionic charge in solution that governs the polysoap micelle structure. Such control would be critical for nanocarrier applications, such as drug delivery and water remediation.

Amphiphilic multi-targeting copolymer micelles efficiently deliver pZNF580 to promote endothelial cell proliferation and migration.

Cationic copolymers are widely used in gene delivery as a non-viral gene vector, but their applications are limited by low transfection efficiency and high cytotoxicity. In order to enhance the transfection efficiency of copolymer micelles to endothelial cells (HUVECs) and reduce their cytotoxicity, this study synthesized an amphipathic multi-targeted copolymer micelle delivery system PCLMD-PPEGMA-NLS-TAT-REDV (TCMs). Gel test results showed that TCMs showed good pZNF580 binding ability and could effectively load the pZNF580 plasmid. The CCK-8 results show that when the concentration of TCMs is greater than 60 μg mL-1, it will affect cell viability and have low cytotoxicity. We found that the multi-targeted copolymer micelles can be effectively taken up by HUVECs in vitro. The transfection efficiency of TCMs@pZNF580 (w/wpZNF580 = 3) to HUVECs was comparable to that of the positive control group lip2000@pZNF580, and WB also showed the same trend. In addition, the TCMs@pZNF580 complex also significantly enhanced the proliferation and migration of HUVECs. The experimental results on blood vessel formation showed that TCMs@pZNF580 accelerated the vascularization of HUVECs. This experiment provided a new technology platform for targeted gene therapy, especially for endothelialization and vascularization. The research results have important reference value for the treatment of cardiovascular diseases.

Copolymer Micelles: A Focus on Recent Advances for Stimulus-Responsive Delivery of Proteins and Peptides.

Historically used for the delivery of hydrophobic drugs through core encapsulation, amphiphilic copolymer micelles have also more recently appeared as potent nano-systems to deliver protein and peptide therapeutics. In addition to ease and reproducibility of preparation, micelles are chemically versatile as hydrophobic/hydrophilic segments can be tuned to afford protein immobilization through different approaches, including non-covalent interactions (e.g., electrostatic, hydrophobic) and covalent conjugation, while generally maintaining protein biological activity. Similar to many other drugs, protein/peptide delivery is increasingly focused on stimuli-responsive nano-systems able to afford triggered and controlled release in time and space, thereby improving therapeutic efficacy and limiting side effects. This short review discusses advances in the design of such micelles over the past decade, with an emphasis on stimuli-responsive properties for optimized protein/peptide delivery.

Multi-fractal modeling of curcumin release mechanism from polymeric nanomicelles

The physicochemical properties of “smart” or stimuli-sensitive amphiphilic copolymers can be modeled as a function of their environment. In special, pH-sensitive copolymers have practical applications in the biomedical field as drug delivery systems. Interactions between the structural units of any polymer-drug system imply mutual constraints at various scale resolutions and the nonlinearity is accepted as one of the most fundamental properties. The release kinetics, as a function of pH, of a model active principle, i.e., Curcumin, from nanomicelles obtained from amphiphilic pH-sensitive poly(2-vinylpyridine)-b-poly(ethylene oxide) (P2VP-b-PEO) tailor-made diblock copolymers was firstly studied by using the Rietger-Peppas equation. The value of the exponential coefficient, n, is around 0.5, generally suggesting a diffusion process, slightly disturbed in some cases. Moreover, the evaluation of the polymer-drug system’s nonstationary dynamics was caried out through harmonic mapping from the usual space to the hyperbolic one. The kinetic model we developed, based on fractal theory, fits very well with the experimental data obtained for the release of Curcumin from the amphiphilic copolymer micelles in which it was encapsulated. This model is a variant of the classical kinetic models based on the formal kinetics of the process.

Non-swelling, super-tough, self-healing, and multi-responsive hydrogels based on micellar crosslinking for smart switch and shape memory

Non-swelling super-tough polymer hydrogels have great potentials for stable applications in wet conditions. It has been challenging since most polymer hydrogels uptake water from the environment and swell, which deteriorates the mechanical strength and toughness. Here, we present multi-responsive non-swelling polymer hydrogels (PHFGs) by using amphiphilic triblock copolymer micelles as non-covalent crosslinkers. Pluronic F127 (or polyethylene oxide-block-polypropylene oxide-block-polyethylene oxide, PEO-PPO-PEO) (F-127) micelles are used as a prototype for the synthesis of micelle-crosslinked poly-(2-hydroxyethylene methacrylate) (PHEMA) hydrogels, without using any modification of F-127 or other crosslinkers. FT-IR and 1H NMR studies provide first evidence that F-127 micelles form extensive hydrogen bonding and hydrophobic association with PHEMA chains. The non-covalent crosslinked hydrogels show a high fracture elongation about 460 %, a fracture strength about 240 kPa, and a fracture toughness about 660 kJ/m3. Negligible swelling is observed for the polymer hydrogels in aqueous solutions. The hydrogels are self-healable, and responsive to variations in pH or water content to change volume, shape, and transparency. Such multiple-responsive polymer hydrogels are utilized as smart switches and shape memory materials that are actuated by environmental stimuli in a controllable manner.

Structure of micelleplexes formed between QPDMAEMA-b-PLMA amphiphilic cationic copolymer micelles and DNA of different lengths

We study the structures of micelleplexes formed by quaternized poly(2-(dimethylamino) ethyl methacrylate)-b-poly(lauryl methacrylate) (QPDMAEMA-b-PLMA) amphiphilic cationic copolymer micelles interacting electrostatically with linear DNA of different lengths (113 and 2000 base pairs). QPDMAEMA-b-PLMA copolymers form micelles in aqueous milieu, with PLMA hydrophobic cores and QPDMAEMA cationic coronas. Nanosized micelleplexes were formed after mixing QPDMAEMA-b-PLMA micelles with DNAs, in a wide range of N/P ratios (nitrogen (N) of amine group of QPDMAEMA over phosphate (P) groups of DNA), as shown by Ultraviolet–Visible (UV–Vis) and fluorescence spectroscopy. Light scattering techniques demonstrated the formation of well-defined micelleplexes with monomodal and narrow size distributions, whose size and surface charge vary according to the N/P ratio. Micelleplexes presented stability under certain salt concentration. Spherical and worm-like micelleplexes were visualized by cryogenic transmission electron microscopy (Cryo-TEM). Overall, QPMDAEMA-b-PLMA micelles can efficiently interact with DNA. The stability, morphology and complexation of the micelleplexes were found to depend on copolymer molecular mass, the hydrophilic/hydrophobic ratio, the micellar structure, the length of DNA, the N/P ratio and the ionic strength. The findings demonstrate that QPDMAEMA-b-PLMA polyelectrolyte copolymer micelles have prospects for their application as non-viral vectors for nucleic acids delivery and gene therapy.

Amphiphilic Random-Block Copolymer Micelles in Water: Precise and Dynamic Self-Assembly Controlled by Random Copolymer Association

Amphiphilic Random-Block Copolymer Micelles in Water: Precise and Dynamic Self-Assembly Controlled by Random Copolymer Association

Hollow polypyrrole coated with mesoporous silica nanoparticles graft copolymer multifunctional nanocomposites for intracellular cancer therapy

A novel hollow polypyrrole coated by mesoporous silica nanoparticles graft poly(2-(4-formylbenzoyloxy)ethyl methacrylate- co -2-(dimethylamino)ethyl methacrylate)- block -poly(triethylene glycol methyl ether methacrylate) multifunctional nanocomposite (HPPy@MSN-SS-NH- g -P(FBEMA- co -DMAEMA)- b -PTEGMA) was designed and prepared via disulfide bond linkages. This material as a gatekeeper integrated multifunctionality such as pore capping, and pH and potothermal multistimuli response abilities, and possessed good photothermal stability, near-infrared (NIR) photothermal conversion capacity and dispersion stability in aqueous solution. It could entrap anticancer doxorubicin (DOX) by pore channels of HPPy@MSN, the core of amphiphilic copolymer micelles and Schiff base linkages, offering a load capacity and load efficiency of up to about 41.5 and 83.1%, respectively. Dynamic light scattering analysis showed that the DOX-loaded preparations had particle size of less than 300 nm, and could achieve intracellular chemo–photothermal combination therapy by controlling the mesopore on-off based on the gatekeepers, tumor environments including pH and reductant stimuli. The drug-loaded nanoparticles exhibited optimal drug release dynamics in cancer tissues upon triggered by pH and glutathione (GSH) under the NIR irradiation. Cell counting Kit-8 assay manifested that the nanocarriers are non-toxic and safe, whereas the drug-loaded preparations exhibited robust anticancer efficacy. Cellular uptake and TUNEL assay revealed high concentrations of DOX accumulating around and inside Hela cells, accordingly producing significant tumor cell apoptosis. Therefore, the newly-developed materials can be used for comprehensive therapy of cancer as a promising candidate of drug delivered carriers. • We prepared hollow PPy coated with MSNs graft copolymer multifunctional composites. • The nanocomposites exhibited pH, reductant and potothermal multi-responsivities. • This material entrapped DOX by pores, hydrophobic actions and Schiff base linkages. • The drug release was triggered by synergism of pore capping, pH, reductant and NIR. • A chemo–photothermal combination therapy could be achieved by the mesopore on-off.

A novel polymer micelle as a targeted drug delivery system for 10-hydroxycamptothecin with high drug-loading properties and anti-tumor efficacy

A novel polyethylene glycol-polycaprolactone-poly-l-tyrosine (MPEG-PCL-PTyr) amphiphilic triblock copolymer micelle was synthesized for the first time. 10-hydroxycamptothecin (HCPT) was embedded in MPEG-PCL-PTyr nanomicelles using the emulsion solvent evaporation method. A series of was conducted to confirm the structure of the compound and to evaluate the physical properties of the MPEG-PCL-PTyr nanomicelles. Cellular uptake, cytotoxicity, and apoptosis were assessed using flow cytometry and MTT assays. Confocal microscopy and flow cytometry results demonstrated that the nanocapsules carrying HCPT had significantly increased anti-tumor activity against HepG2 cells and could target HepG2 cell lysosomes with obvious liver targeting. In addition, the drug-loaded nanomicelles could significantly block the S phase of cancer cells and induce apoptosis; thus, they could be potential carriers for future 10-HCPT delivery and cancer treatment.

Tenoxicam-loaded polymeric micelles material: Formulation, optimization, and evaluation

The objective of the current study was to encapsulate Tenoxicam a poorly soluble drug within self-assembled polymeric micelles created from amphiphilic block copolymer poloxamer 407 to enhance its solubility and thus increasing oral bioavailability. Thin-film hydration technique was adapted in preparation of Tenoxicam loaded polymeric micelles based on different ratios of copolymer poloxamer 407 (ranging from 1:5 up to 1:90), selection of the best micellar formula was based on the values of entrapment efficiency (EE%), particle size (PS), polydispersity index (PDI), and rate of in vitro drug release, then lyophilization was done for selected formula. Prepared micellar solutions (PM1-PM10) were characterized and the best formula PM6 was chosen according to good EE% (84.05%), smaller particle size (33.07 ± 2.23 nm), lower PDI value (0.155), and higher in vitro drug release (81.43% ± 0.048), which further lyophilized and subjected for powder characterization. Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) indicated that TNX was encapsulated in polymeric micelle core, due to the disappearance of a characteristic peak of TNX. Saturated solubility of PM6 lyophilized powder showed an increase in aqueous solubility (122 times) compared with pure drug, while transmission electron microscopy (TEM) showed the polymeric micelles in images with a spherical structure, smooth surface, uniform particle size, and homogeneous distribution in an aqueous medium. It was concluded that the prepared amphiphilic copolymer micelles loaded with TNX exhibited significant improvement in drug solubility and consequently may enhance oral bioavailability and suggested to be used to prepare solid oral dosage form as an alternative to the marketed one with lower dose size and reduce drug side effects.

Synthesis of ordered mesoporous carbon by soft template method

Much attention has been given to mesoporous carbons incorporated through soft template method because of its simple blend and easy power over the determined porous framework. Related to delicate template methods for mesoporous oxides of metal, its combination depends upon succession of shaping molecular plan of action of precursor species with delicate layouts, adjustment of the precursor system by polymerization lastly the template expulsion. Utilizing micelles of amphiphilic square copolymers as templates, effortless command over the structure and size of mesopores can be accomplished and centralization of the polymer template or synthesis and level of precursor polymerization. We depict recent synthesis models and use of mesoporous carbon materials prepared by soft template method. In addition, we emphasize central standards of self-accumulation, feature proposed blend components and present methods for regulating pore size.

Thermoresponsive Gelation of Amphiphilic Random Copolymer Micelles in Water

Herein, we developed thermoresponsive gelation systems of amphiphilic random copolymer micelles in water. To establish the design of micelle nanodomains for the physical gels, we synthesized random...

Self‐assembly mechanism of PEG‐b‐PCL and PEG‐b‐PBO‐b‐PCL amphiphilic copolymer micelles in aqueous solution from coarse grain modeling

AbstractWe followed the self‐assembly of high‐molecular weight MePEG‐b‐PCL (poly(methyl ethylene glycol)‐block‐poly(ε‐caprolactone)) diblock and MePEG‐b‐PBO‐b‐PCL (poly(methyl ethylene glycol)‐block‐poly(1,2‐butylene oxide)‐block‐poly(ε‐caprolactone)) into micelles using molecular dynamics simulation with a coarse grain (CG) force field based on quantum mechanics (CGq FF). The triblock polymer included a short poly(1,2‐butylene oxide) (PBO) at the hydrophilic‐hydrophobic interface of these systems. Keeping the hydrophilic length fixed (MePEG45), we considered 250 chains in which the hydrophobic length changed from PCL44 or PBO6‐b‐PCL43 to PCL62 or PBO9‐b‐PCL61. The polymers were solvated in explicit water for 2 μs of simulations at 310.15 K. We found that the longer diblock system undergoes a morphological transition from an intermediate rod‐like micelle to a prolate‐sphere, while the micelle formed from the longer triblock system is a stable rod‐like micelle. The two shorter diblock and triblock systems show similar self‐assembly processes, both resulting in slightly prolate‐spheres. The dynamics of the self‐assembly is quantified in terms of chain radius of gyration, shape anisotropy, and hydration of the micelle cores. The final micelle structures are analyzed in terms of the local density components. We conclude that the CG model accurately describes the molecular mechanisms of self‐assembly and the equilibrium micellar structures of hydrophilic and hydrophobic chains, including the quantity of solvent trapped inside the micellar core.

Synthesis of Ag/fluorine-containing polyacrylate latex stabilized by Ag nanoparticle hybrid amphiphilic random copolymer micelles via Pickering emulsion polymerization and its application on fabric finishing

Ag/fluorine-containing polyacrylate latex was successfully synthesized via Pickering emulsion polymerization using Ag/poly(2-dimethylaminoethyl methacrylate-co-hexafluorobutyl acrylate) (Ag/P(DMAEMA-co-HFBA)) hybrid micelles as particle emulsifiers. The influences of introducing the Ag nanoparticles (NPs) component and the concentration of Ag/P(DMAEMA-co-HFBA) hybrid micelles on emulsion polymerization and finished cotton fabric properties were studied. The results showed that the Ag/fluorine-containing polyacrylate latex had a higher conversion, smaller particle size than the fluorine-containing polyacrylate latex using P(DMAEMA-co-HFBA) micelles as emulsifiers, indicating the positive effect of Ag NPs on emulsion polymerization. And thermogravimetric analysis (TGA) proved that Ag NPs improved the thermal stability of the latex film. Moreover, the surface of the cotton fabric finished by Ag/fluorine-containing polyacrylate latex showed more rough morphology, better hydrophobicity and excellent antibacterial activity owing to the synergistic effect of the cationic fluorine-containing polyacrylate compounds and Ag nanoparticles. Meanwhile, the presence of Ag NPs also improved the tensile strength of the finished cotton fabric, but reduced slightly the whiteness. When the concentration of Ag/P(DMAEMA-co-HFBA) hybrid micelle emulsifier was 8 mg/mL, the Ag/fluorine-containing polyacrylate latex particles presented regular raspberry-shaped with an average diameter of 120 nm, and the water/oil contact angles of finished cotton fabric attained 145° and 90°, respectively. In addition, the finished cotton fabric exhibited excellent antibacterial properties against both S. aureus and E. coli as the concentration of Ag/P(DMAEMA-co-HFBA) hybrid micelles was 12 mg/mL. The mechanism for the formation of Ag/fluorine-containing polyacrylate latex was proposed.

Improved delivery and antimetastatic effects of Stattic by self-assembled amphiphilic pendant-dendron copolymer micelles in breast cancer cell lines

Stattic is a signaling pathway inhibitor that could potentially impede the progression of tumor metastasis. However, the pharmaceutical applications of Stattic are hampered by its poor water solubility. In this study, we explored the integration of Stattic within amphiphilic pendant-dendron copolymeric (P71D3) micelles to improve its water solubility and delivery towards tumor cells. The P71D3/Stattic micelles with a 1:1.2 (P71D3:Stattic) ratio optimized for subsequent studies were 164 nm in diameter with a drug loading percentage of 52% w/w. These P71D3/Stattic micelles demonstrated a higher drug release (32%) in acidic tumor conditions compared to neutral physiological conditions (14%). However, rapid and high Stattic release was observed when dialyzed against a simulated plasma solution containing 4% albumin. Interestingly, when the same Stattic-loaded micelles and 4% albumin solution were in direct contact, the albumin molecules bound to the surface of the micelles, forming a protein corona. P71D3/Stattic micelles were found to be 30- to 90-fold more potent and to decrease the effective antimotility concentration by 3- to 6-fold compared to free Stattic in metastatic human and murine mammary cancer cells. The P71D3/Stattic micelles effectively enhanced the potency of the drug as determined from the in vitro studies, suggesting the use of P71D3/Stattic micelles as a promising antimetastatic agent worthy of further study.

Formation of Copolymer-Ag Nanoparticles Composite Micelles in Three-dimensional Co-flow Focusing Microfluidic Device

A novel method was presented to create composite micelles of amphiphilic copolymers and Ag nanoparticles (NPs) in a three-dimensional co-flow focusing microfluidic device (3D CFMD). Self-assembly of the copolymers was initiated by the fast mixing of water and a blend dispersion of hydrophobic Ag NPs and amphiphilic copolymers. At the same time, the hydrophobic Ag NPs enter the core of copolymer micelles, based on the hydrophobic interaction. The copolymer-Ag NPs composite micelles have a core-shell structure with copolymer shell and Ag NPs core. COMSOL Multiphysics is used to simulate the concentration distribution of copolymers and Ag NPs under different flow rates. Co-assembly microfluidic conditions are determined based on simulation results. Under suitable microfluidic conditions, both block copolymers and gradient copolymers can co-assemble with hydrophobic Ag NPs to form composite micelles, respectively. This microfluidic coassembly method will have a good prospect in the preparation of composite micelles of amphiphilic copolymers and metal nanoparticles.

Synthesis of pH-responsive block copolymer micelles via RAFT polymerization induced self-assembly and its application in emulsifier-free emulsion polymerization

The pH-responsive amphiphilic block copolymer micelles based on poly (2-(dimethylamino) ethyl methacrylate) (PDMAEMA) as a flexible corona and poly(hexafluorobutyl acrylate) (PHFBA) as a core have been synthesized by reversible addition-fragmentation chain transfer polymerization induced self-assembly (RAFT-PISA). This core-shell type amphiphilic copolymer micelles possessed the characteristics of pH-response from pendent tertiary amine groups in PDMAEMA chain. The morphology and size of amphiphilic block copolymer micelles were measured by dynamic light scattering (DLS) and transmission electron microscopy (TEM) analyses. The results indicated that the diameter of micelles narrowed down from 160 nm to 20 nm along with the increased pH value from 1.32 to 2.90. However, the diameter of the amphiphilic block copolymer micelles ranged broadly from 20 nm to more than 100 nm at pH ≥ 5.89. The amphiphilic block copolymer micelles were later used as reactors to synthesize cationic fluorinated polyacrylate emulsifier-free emulsion at pH 2.90, using fluorinated monomers and acrylate monomers as mixed monomers. The latex particles were presented as core-shell morphology with diameter of about 220 nm and narrow distribution, as characterized by TEM and DLS. The obtained emulsion with high zeta potential (+57.8 mV) had excellent stability.

Nanoscale cationic micelles of amphiphilic copolymers based on star-shaped PLGA and PEI cross-linked PEG for protein delivery application.

To enhance the bioavailability of protein therapeutants and improve the stability of storage and delivery, a series of branched amphiphilic block copolymers consisting of cholic acid (CA) initiated poly(D,L-lactide-co-glycolide) (CA-PLGA) and water-soluble polyethyleneimine cross-linked polyethylene glycol (PEI-PEG) denoted as CA-PLGA-b-(PEI-PEG) were synthesized and characterized. CA-PLGA-b-(PEI-PEG) presented low cytotoxicity by MTT and cck-8 assay. The cationic CA-PLGA-b-(PEI-PEG) micelles (diameter about 100 nm and zeta potential 34-61 mV) were prepared through self-assembly method, and complexed with insulin via electrostatic interaction to obtain nanoscale micelle/insulin complexes. The micelle/insulin complexes-loaded CA-PLGA microspheres (MIC-MS, 10.4 ± 3.85 μm) were manufactured by employing a double emulsion (W1/O/W2) method. The in vitro insulin release behavior and in vivo hypoglycaemic effect of MIC-MS on streptozotocin (STZ) induced diabetic rats were compared with those of the insulin-loaded CA-PLGA microspheres (INS-MS, 7.8 ± 2.57 μm). The initial burst in vitro release of MIC-MS was markedly lower than that of INS-MS (P < 0.01), and the pharmacological availability of MIC-MS via subcutaneous administration was 148.9% relative to INS-MS. Therefore, the cationic CA-PLGA-b-(PEI-PEG) micelles can effectively increase the bioavailability of insulin in CA-PLGA microspheres and can be considered as a potential protein carrier.

Photo-controlled release of metal ions using triazoline-containing amphiphilic copolymers

Photo-controlled release of metal ions can be achieved by denitrogenation of triazoline from the micelles of amphiphilic copolymer, and has potential applications for biomedicines.

Preparation of polymer electrolyte membranes with continuous PEG channel via the fusion of self-assembled polycyclooctene-graft-polyethylene glycol copolymer micelles

Small molecular weight polyethylene glycol (PEG 350 g/mol) based polymer electrolyte membranes (PEMs) with continuous lithium ion transport channels are prepared via the fusion of the self-assembled micelles of amphiphilic copolymer. The self-assembled micelles consisted of nonpolar polycyclooctene (PCOE) core and polar PEG shell are formed via dialyzing the dichloromethane solution of amphiphilic polycyclooctene-graft-polyethylene glycol (PCOE-g-PEG) copolymer with ethanol, which is a good solvent for PEG and nonsolvent for PCOE. The resulted electrolyte membrane with bicontinuous morphology is obtained by casting the self-assembled micelle solution in a stainless steel plate and heating at 80 °C for 24 h after mixing with a certain amount of lithium perchlorate (LiClO4). When the content of PEG is 20 wt%, the ion conductivity of the self-assembled PEM can exceed 10−4S/cm at 25 °C, which is 3 orders of magnitude higher than the counter PEM groups prepared via directly casting of the copolymer dichloromethane solution without self-assembled process. While the mechanical strength of the self-assembled PEMs is almost the same as those directly casting ones, in which only PCOE phase is continuous.