Synthesis of pH‐ and temperature‐responsive chitosan‐graft‐poly[2‐(N,N‐dimethylamino) ethyl methacrylate] copolymer and gold nanoparticle stabilization by its micelles

Novel pH‐ and temperature‐responsive chitosan‐graft‐poly[2‐(N,N‐dimethylamino)ethyl methacrylate] (chitosan‐g‐PDMAEMA) copolymers were successfully synthesized by homogeneous atom transfer radical polymerization (ATRP) under mild conditions. Chitosan macroinitiator was prepared by phthaloylation of amino groups of chitosan and subsequent acylation of hydroxyl groups of chitosan with 2‐bromoisobutyryl bromide. The copolymers were obtained by ATRP of 2‐(N,N‐dimethylamino)ethyl methacrylate and they can self‐assemble into stable micelles in water. Hybrid micelles with a PDMAEMA corona incorporating gold nanoparticles (Au NPs) were prepared in situ via the reduction of HAuCl₄ with NaBH₄. The pH and temperature responses of the copolymer micelles and hybrid micelles were characterized using UV‐visible spectroscopy and dynamic laser light scattering. The morphology of the micelles was observed using transmission electron microscopy and atomic force microscopy. The PDMAEMA corona of the micelles acts as the ‘nanoreactor’ and the ‘anchor’ for the in situ formation and stabilization of Au NPs. Therefore, the spatial distribution of Au NPs within the micelles can be tuned by varying the temperature and pH value. Copyright © 2010 Society of Chemical Industry     

Synthesis of well‐defined comb‐like amphiphilic copolymers with protonizable units in the pendent chains: 2. Poly(2‐(dimethylamino)ethyl methacrylate) grafted poly(methyl methacrylate‐co‐2‐hydroxyethyl methacrylate) copolymers and their association behavior in aqueous solution

Narrow‐distribution, well‐defined comb‐like amphiphilic copolymers are reported in this work. The copolymers are composed of poly(methyl methacrylate‐co‐2‐hydroxyethyl methacrylate) (P(MMA‐co‐HEMA)) as the backbones and poly(2‐(dimethylamino)ethyl methacrylate) (PDMAEMA) as the grafted chains, with the copolymer backbones being synthesized via atom‐transfer radical polymerization (ATRP) and the grafted chains by oxyanionic polymerization. The copolymers were characterized by gel permeation chromatography (GPC), Fourier‐transform infrared (FT‐IR) spectroscopy and ¹H NMR spectroscopy. The aggregation behavior in aqueous solutions of the comb‐like amphiphilic copolymers was also investigated. ¹H NMR spectroscopic and surface tension measurements all indicated that the copolymers could form micelles in aqueous solutions and they possessed high surface activity. The results of dynamic light scattering (DLS) and scanning electron microscopy (SEM) investigations showed that the hydrodynamic diameters of the comb‐like amphiphilic copolymer aggregates increased with dilution. Because of the protonizable properties of the graft chains, the surface activity properties and micellar state can be easily modulated by variations in pH. Copyright © 2004 Society of Chemical Industry     

Synthesis and characterization of thermo‐ and pH‐sensitive block copolymers bearing a biotin group at the poly(ethylene oxide) chain end

A poly(ethylene oxide)‐block‐poly(dimethylamino ethyl methacrylate) block copolymer (PEO‐b‐PDMAEMA) bearing an amino moiety at the PEO chain end was synthesized by a one‐pot sequential oxyanionic polymerization of ethylene oxide (EO) and dimethylamino ethyl methacrylate (DMAEMA), followed by a coupling reaction between its PEO amino and a biotin derivative. The polymers were charac terized with ¹H NMR spectroscopy and gel permeation chromatography. Activated biotin, biotin‐NHS (N‐hydroxysuccinimide), was used to synthesize biotin‐PEO‐PDMAEMA. In aqueous media, the solubility of the copolymer was temperature‐ and pH‐sensitive. The particle size of the micelle formed from functionalized block copolymers was determined by dynamic light scattering. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 3552–3558, 2006     

Temperature,pH, and reduction triple‐stimuli‐responsive inner‐layer crosslinked micelles as nanocarriers for controlled release

Temperature, pH, and reduction triple‐stimuli‐responsive inner‐layer crosslinked micelles as nanocarriers for drug delivery and release are designed. The well‐defined tetrablock copolymer poly(polyethylene glycol methacrylate)–poly[2‐(dimethylamino) ethyl methacrylate]–poly(N‐isopropylacrylamide)–poly(methylacrylic acid) (PPEGMA‐PDMAEMA‐PNIPAM‐PMAA) is synthesized via atom transfer radical polymerization, click chemistry, and esterolysis reaction. The tetrablock copolymer self‐assembles into noncrosslinked micelles in acidic aqueous solution. The core‐crosslinked micelles, shell‐crosslinked micelles, and shell–core dilayer‐crosslinked micelles are prepared via quaternization reaction or carbodiimide chemistry reaction. The crosslinked micelles are used as drug carriers to load doxorubicin (DOX), and the drug encapsulation efficiency with 20% feed ratio reached 59.2%, 73.1%, and 86.1%, respectively. The cumulative release rate of DOX is accelerated by single or combined stimulations. The MTT (3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay verifies that the inner‐layer crosslinked micelles show excellent cytocompatibility, and DOX‐loaded micelles exhibit significantly higher inhibition for HepG2 cell proliferation. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46714.     

Synthesis of a poly(methyl methacrylate)‐b‐poly[2‐(N,N‐dimethylamino) ethyl methacrylate] block copolymer and its effects on the surface charges and pH‐responsive properties of poly(vinylidene fluoride) blend membranes

A poly(methyl methacrylate) (PMMA)‐b‐poly[2‐(N,N‐dimethylamino) ethyl methacrylate] (PDMAEMA) block copolymer was successfully synthesized by a reversible addition–fragmentation chain‐transfer method. The resulting copolymer was used to prepare poly(vinylidene fluoride) blend membranes via a phase‐inversion technique. The polymorphism, structure, and properties of the blend membranes were investigated by Fourier transform infrared spectrometry, scanning electron microscopy (SEM), ζ potential analysis, and filtration. The results indicate that PMMA‐b‐PDMAEMA could migrate onto the surface of the membrane during the coagulation process, and more of the β‐crystal phase appeared with the increase of the block copolymer in the membranes. The surface morphology and cross section of the membranes were also affected by the copolymer, as shown by SEM. The ζ‐potential results show that the surface charges of the membrane could be changed from positive to negative at an isoelectric point as the pH increased. The blend membrane also exhibited good pH sensitivity, and its water flux showed a great dependence on pH. The filtration experiment also indicated that the blend membrane had good hydrophilicity and antifouling properties. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40685.     

Poly(N‐isopropylacrylamide‐co‐hydroxyethyl methacrylate) graft copolymers and their application as carriers for drug delivery system

Poly(N‐isopropylacrylamide‐co‐hydroxyethyl methacrylate) [P(NIPAM‐co‐HEMA)] copolymer was synthesized by controlled radical polymerization from respective N‐isopropylacrylamide (NIPAM) and hydroxyethyl methacrylate (HEMA) monomers with a predetermined ratio. To prepare the thermosensitive and biodegradable nanoparticles, new thermosensitive graft copolymer, poly(L ‐lactide)‐graft‐poly(N‐isoporylacrylamide‐co‐hydroxyethyl methacrylate) [PLLA‐g‐P(NIPAM‐co‐HEMA)], with the lower critical solution temperature (LCST) near the normal body temperature, was synthesized by ring opening polymerization of L ‐lactide in the presence of P(NIPAM‐co‐HEMA). The amphiphilic property of the graft copolymers was formed by the grafting of the PLLA hydrophobic chains onto the PNIPAM based hydrophilic backbone. Therefore, the graft copolymers can self‐assemble into uniformly spherical micelles ò about 150–240 nm in diameter as observed by the field emission scanning electron microscope and dynamic light scattering. Dexamethasone can be loaded into these nanostructures during dialysis with a relative high loading capacity and its in vitro release depends on temperature. Above the LCST, most of the drugs were released from the drug‐loaded micelles, whereas a large amount of drugs still remains in the micelles after 48 h below the LCST. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Synthesis and characterization of poly(dimethylamino ethyl methacrylate)–poly(ethylene oxide)–poly(dimethylamino ethyl methacrylate) triblock copolymers

Novel, monodispersed, and well‐defined ABA triblock copolymers [poly(dimethylamino ethyl methacrylate)–poly(ethylene oxide)–poly(dimethylamino ethyl methacrylate)] were synthesized by oxyanionic polymerization with potassium tert‐butanoxide as the initiator. Gel permeation chromatography and ¹H‐NMR analysis showed that the obtained products were the desired copolymers with molecular weights close to calculated values. Because the poly(dimethylamino ethyl methacrylate) block was pH‐ and temperature‐sensitive, the aqueous solution behavior of the polymers was investigated with ¹H‐NMR and dynamic light scattering techniques at different pH values and at different temperatures. The micelle morphology was determined with transmission electron microscopy. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Synthesis and thermal properties of poly(methyl methacrylate)‐poly(L‐lactic acid)‐poly(methyl methacrylate) tri‐block copolymer

Poly(methyl methacrylate)‐poly(L ‐lactic acid)‐poly(methyl methacrylate) tri‐block copolymer was prepared using atom transfer radical polymerization (ATRP). The structure and properties of the copolymer were analyzed using infrared spectroscopy, gel permeation chromatography, nuclear magnetic resonance (¹H‐NMR, ¹³C‐NMR), thermogravimetry, and differential scanning calorimetry. The kinetic plot for the ATRP of methyl methacrylate using poly(L ‐lactic acid) (PLLA) as the initiator shows that the reaction time increases linearly with ln[M]₀/[M]. The results indicate that it is possible to achieve grafted chains with well‐defined molecular weights, and block copolymers with narrowed molecular weight distributions. The thermal stability of PLLA is improved by copolymerization. A new wash‐extraction method for removing copper from the ATRP has also exhibits satisfactory results. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Self‐assembled micelles prepared from poly(ɛ‐caprolactone)–poly(ethylene glycol) and poly(ɛ‐caprolactone/glycolide)–poly(ethylene glycol) block copolymers for sustained drug delivery

A series of poly(?‐caprolactone)–poly(ethylene glycol) (PCL‐PEG) and poly(?‐caprolactone/glycolide)–poly(ethylene glycol) [P(CL/GA)‐PEG] diblock copolymers were prepared by ring‐opening polymerization of ?‐caprolactone or a mixture of ?‐caprolactone and glycolide using monomethoxy PEG (mPEG) as macroinitiator and Sn(Oct)₂ as catalyst. The resulting copolymers were characterized using ¹H‐NMR, gel permeation chromatography, differential scanning calorimetry, and wide‐angle X‐ray diffraction. Copolymer micelles were prepared using the nanoprecipitation method. The morphology of the micelles was spherical or worm‐like as revealed by transmission electron microscopy, depending on the copolymer composition and the length of the hydrophobic block. Introduction of the glycolide component, even in small amounts (CL/GA = 10), disrupted the chain structure and led to the formation of spherical micelles. Interestingly, the micelle size decreased with the encapsulation of paclitaxel. Micelles prepared from mPEG5000‐derived copolymers exhibited better drug loading properties and slower drug release than those from mPEG2000‐derived copolymers. Drug release was faster for copolymers with shorter PCL blocks than for those with longer PCL chains. The introduction of glycolide moieties enhanced drug release, but the overall release rate did not exceed 10% in 30 days. In contrast, drug release was enhanced in acidic media. Therefore, these bioresorbable micelles and especially P(CL/GA)‐PEG micelles with excellent stability, high drug loading content, and prolonged drug release could be promising for applications as drug carriers. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45732.     

Fabrication of micelles from poly(butylene succinate) and poly(2‐methacryloyloxyethyl phosphorylcholine) copolymers as a potential drug carrier

A series of copolymers of poly(2‐methacryloyloxyethyl phosphorylcholine)‐b‐poly(butylene succinate)‐b‐poly(2‐methacryloyloxyethyl phosphorylcholine) (PMPC‐b‐PBS‐b‐PMPC) were synthesized by atom transfer radical polymerization. The structure of the polymers was characterized by ¹H NMR and infrared spectroscopy, and their thermal properties were described using TGA and DSC. In aqueous solutions, the PMPC‐b‐PBS‐b‐PMPC could form micelles with sizes ranging from 108 to 170 nm. In vitro release studies showed that acidic media and a longer PMPC chain benefited doxorubicin (DOX) release. 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assays indicated that the micelles had low cytotoxicity to HeLa and L929 cells. DOX‐loaded micelles exhibited high cytotoxicity to HeLa cells. Flow cytometry results demonstrated that DOX‐loaded micelles could be internalized by HeLa cells. The in vitro phagocytosis results showed 3.9‐fold and 5.5‐fold reductions compared with poly(lactic acid) (PLA) nanoparticles and PDS55 micelles. These results demonstrate that PMPC‐b‐PBS‐b‐PMPC block copolymer micelles have great promise for cancer therapy. © 2017 Society of Chemical Industry     

Application of the biodegradable diblock copolymer poly(L‐lactide)‐block‐poly(L‐cysteine): Drug delivery and protein conjugation

A novel approach to self‐assembled and shell‐crosslinked (SCL) micelles from the diblock copolymer poly(L ‐lactide)‐block‐poly(L ‐cysteine) to be used as drug and protein delivery carriers is described. Rifampicin was used as a model drug. The drug‐loaded SCL micelles were obtained by self‐assembly of the copolymer in the presence of the drug in aqueous media. Their morphology and size were studied with dynamic light scattering and field emission scanning electron microscopy. The rifampicin loading capacity and encapsulation efficiency were studied with ultraviolet–visible spectrophotometry. The drug‐release rate in vitro depended on the oxidizing and reducing environment. Moreover, a straightforward approach to the conjugation of the copolymer with bovine serum albumin (BSA) was developed, and a gel electrophoresis test demonstrated that this conjugated BSA could be reversibly released from the copolymer substrate under reducing conditions. In conclusion, this L ‐cysteine copolymer can be used in drug delivery and in protein fixation and recovery. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Synthesis and surface properties of polydimethylsiloxane‐based block copolymers: poly[dimethylsiloxane‐block‐ (ethyl methacrylate)] and poly[dimethylsiloxane‐block‐(hydroxyethyl methacrylate)]

A polydimethylsiloxane (PDMS) macroazoinitiator was synthesized from bis(hydroxyalkyl)‐terminated PDMS and 4,4′‐azobis‐4‐cyanopentanoic acid by a condensation reaction. The bifunctional macroinitiator was used for the block copolymerization of ethyl methacrylate (EMA) and 2‐(trimethylsilyloxy)ethyl methacrylate (TMSHEMA) monomers. The poly(DMS‐block‐EMA) and poly(DMS‐block‐TMSHEMA) copolymers thus obtained were characterized using Fourier transform infrared and ¹H NMR spectroscopy and differential scanning calorimetry. After the deprotection of trimethylsilyl groups, poly(DMS‐block‐HEMA) and poly(DMS‐block‐EMA) copolymer film surfaces were analysed using scanning electron microscopy and X‐ray photoelectron spectroscopy. The effects of the PDMS concentration in the copolymers on both air and glass sides of films were examined. The PDMS segments oriented and moved to the glass side in poly(DMS‐block‐EMA) copolymer film while orientation to the air side became evident with increasing DMS content in poly(DMS‐block‐HEMA) copolymer film. The block copolymerization technique described here is a versatile and economic method and is also applicable to a wide range of monomers. The copolymers obtained have phase‐separated morphologies and the effects of DMS segments on copolymer film surfaces are different at the glass and air sides. Copyright © 2010 Society of Chemical Industry     

Preparation of new dendrimer‐like star‐shaped amphiphilic poly(ethylene glycol)–poly(ϵ‐caprolactone) copolymers for biocompatible and high‐efficiency curcumin delivery

Novel amphiphilic star‐shaped terpolymers comprised of hydrophobic poly(?‐caprolactone), pH‐sensitive polyaminoester block and hydrophilic poly(ethylene glycol) (M_n = 1100, 2000 g mol^?1) were synthesized using symmetric pentaerythritol as the core initiator for ring‐opening polymerization (ROP) reaction of ?‐caprolactone functionalized with amino ester dendrimer structure at all chain ends. Subsequently, a second ROP reaction was performed by means of four‐arm star‐shaped poly(?‐caprolactone) macromer with eight ‐OH end groups as the macro‐initiator followed by the attachment of a poly(ethylene glycol) block at the end of each chain via a macromolecular coupling reaction. The molecular structures were verified using Fourier transform infrared and ¹H NMR spectroscopies and gel permeation chromatography. The terpolymers easily formed core–shell structural nanoparticles as micelles in aqueous solution which enhanced drug solubility. The hydrodynamic diameter of these agglomerates was found to be 91–104 nm, as measured using dynamic light scattering. The hydrophobic anticancer drug curcumin was loaded effectively into the polymeric micelles. The drug‐loaded nanoparticles were characterized for drug loading content, encapsulation efficiency, drug–polymer interaction and in vitro drug release profiles. Drug release studies showed an initial burst followed by a sustained release of the entrapped drug over a period of 7days at pH = 7.4 and 5.5. The release behaviours from the obtained drug‐loaded nanoparticles indicated that the rate of drug release could be effectively controlled by pH value. Altogether, these results demonstrate that the designed nanoparticles have great potential as hydrophobic drug delivery carriers for cancer therapy. © 2015 Society of Chemical Industry     

Structure–property relationship of pH‐sensitive (PCL)2(PDEA‐b‐PPEGMA)2 micelles: Experiment and DPD simulation

The experiment and dissipative particle dynamics simulation were carried out on four polymers with different block ratios for the investigation of the structure–property relationship of (poly(ε‐caprolactone)₂‐[poly(2‐(diethylamino)ethyl methacrylate)‐b‐poly(poly(ethylene glycol) methyl ether methacrylate)]₂ [(PCL)₂(PDEA‐b‐PPEGMA)₂] micelles. The miktoarm star polymers assembled into spherical micelles composed of PCL core, pH‐sensitive PDEA mesosphere and poly (ethylene glycol) methyl ether methacrylate (PPEGMA) shell. When decreasing pH from 7.4 to 5.0, the hydrodynamic diameter and transmittance of (PCL)₂(PDEA‐b‐PPEGMA)₂ micelles increased along with globule‐uneven‐extended conformational transitions, owing to the protonation of tertiary amine groups of DEA at lower pH conditions. Doxorubicin (DOX) was mainly loaded in the pH‐sensitive layer, and more DOX were loaded in the core when increasing drug concentrations. The in vitro DOX release from the micelles was significantly accelerated by decreasing pH from 7.4 to 5.0. The results demonstrated that the pH‐sensitive micelles could be used as an efficient carrier for hydrophobic anticancer drugs, achieving controlled and sustained drug release. © 2014 American Institute of Chemical Engineers AIChE J, 60: 3634–3646, 2014     

Surfactant‐free nanoparticles of poly(DL‐lactide‐co‐glycolide) prepared with poly(L‐lactide)/ poly(ethylene glycol)

Surfactant‐free nanoparticles of poly(DL ‐lactide‐co‐glycolide) (PLGA) nanoparticles were prepared with or without poly(L ‐lactide)‐poly(ethylene oxide) (LE) diblock copolymer (abbreviated as PLGA/LE and PLGA nanoparticles) by dialysis method. LE diblock copolymer was used to make PLGA nanoparticles to alternate conventional surfactant. The size of PLGA and PLGA/LE nanoparticles was 295.3 ± 171.3 and 307.6 ± 27.2 nm, respectively, suggesting LE diblock copolymer might be coated onto the surface of nanoparticles. Observation of scanning electron microscope (SEM) showed that PLGA/LE nanoparticles have spherical shapes ranging ～ 200–500 nm. In ¹H‐NMR study, characteristic peaks of the methyl protons of PLGA disappeared in D₂O, whereas characteristic peaks of the methyl proton of both PEG and PLGA were shown in both CDCl₃ and D₂O, indicating that LE diblock copolymer coated on the surface of the PLGA nanoparticles. The higher the initial content of drug, the higher the drug contents and the lower the loading efficiency. PLGA/LE nanoparticles at higher drug contents resulted in slower adriamycin·HCl (ADR) release rate than that of lower drug contents. Also, slower release rate of ADR was achieved by entrapped into the PLGA/LE nanoparticles, whereas LE polymeric micelles showed rapid ADR release. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 1116–1123, 2003     

Synthesis,characterization, and application of novel amphiphilic poly(D‐gluconamidoethyl methacrylate)‐b‐polyurethane‐b‐ poly(D‐gluconamidoethyl methacrylate) triblock copolymers

Novel amphiphilic ABA‐type poly(D ‐gluconamidoethyl methacrylate)‐b‐polyurethane‐b‐poly(D ‐gluconamidoethyl methacrylate) (PGAMA‐b‐PU‐b‐PGAMA) tri‐block copolymers were successfully synthesized via the combination of the step‐growth and copper‐catalyzed atom transfer radical polymerization (ATRP). Dihydroxy polyurethane (HO‐PU‐OH) was synthesized by the step‐growth polymerization of hexamethylene diisocyanate with poly(tetramethylene glycol). PGAMA‐b‐PU‐b‐PGAMA block copolymers were synthesized via copper‐catalyzed ATRP of GAMA in N, N‐dimethyl formamide at 20°C in the presence of 2, 2′‐bipyridyl using Br‐PU‐Br as macroinitiator and characterized by ¹H‐NMR spectroscopy and GPC. The resulting block copolymer forms spherical micelles in water as observed in TEM study, and also supported by ¹H NMR spectroscopy and light scattering. Miceller size increases with increase in hydrophilic PGAMA chain length as revealed by DLS study. The critical micellar concentration values of the resulting block copolymers increased with the increase of the chain length of the PGAMA block. Thermal properties of these block copolymers were studied by thermo‐gravimetric analysis, and differential scanning calorimetric study. Spherical Ag‐nanoparticles were successfully synthesized using these block copolymers as stabilizer. The dimension of Ag nanoparticle was tailored by altering the chain length of the hydrophilic block of the copolymer. A mechanism has been proposed for the formation of stable and regulated Ag nanoparticle using various chain length of hydrophilic PGAMA block of the tri‐block copolymer. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Drug‐delivery system based on core–shell‐type nanoparticles composed of poly(γ‐benzyl‐L‐glutamate) and poly(ethylene oxide)

A block copolymer based on poly(γ‐benzyl‐L ‐glutamate) (PBLG) as the hydrophobic part and poly(ethylene oxide) (PEO) as the hydrophilic part was synthesized and characterized. PBLG/PEO/PBLG (GEG) block copolymer nanoparticles were prepared using the dialysis technique. Fluorescence spectroscopy measurement suggested that GEG block copolymers were associated in water to form polymeric micelles and the critical micelle concentration (CMC) value of the GEG‐50 block copolymer was 0.0084 g/L. Particle‐size distribution of the GEG‐50 block copolymer based on the number average was 34.9 ± 17.6 nm. Also, the particle size and drug‐loading contents of GEG nanoparticles were significantly changed with the initial solvent used. From transmission electron microscope (TEM) observations, the GEG polymeric micelle was a nice spherical shape and the sizes ranged from approximately 20–60 nm in diameter. Results from assessing the drug‐loading contents against the initial solvent showed that the use of tetrahydrofuran (THF) or 1,4‐dioxane as the initial solvent resulted in higher drug‐loading contents than those of other solvents. In the drug‐release studies, the higher the molecular weight of the polymer and drug‐loading contents, the slower the drug release. Also, the initial solvent used was significantly affected not only in the drug‐loading contents but also in the drug‐release kinetics. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 75: 1115–1126, 2000     

Two‐component “Onionlike” micelles with a PPO core,a PDMAEMA shell and a PEO corona: formation and crosslinking

BACKGROUND: Chemical or physical crosslinking of supramolecular assemblies gives them stability in a wide range of environments. Much attention is paid to multilayer (onion‐like) polymeric micelles because their functionality is higher than classic core‐shell micelles. This work reports on the formation and crosslinking of onion‐like micelles prepared by mixing two different block copolymers containing a crosslinkable poly(dimethylaminoethyl methacrylate) (PDMAEMA) block. RESULTS: Block copolymers of a crosslinkable PDMAEMA block were synthesized by atom transfer radical polymerization of 2‐(dimethylamino)ethyl methacrylate (DMAEMA) from poly(propylene oxide) (PPO) or poly(ethylene oxide) (PEO) macroinitiators. The (PDMAEMA₁₃)‐block‐PPO₆₉‐block‐(PDMAEMA₁₃) triblock formed wormlike core‐shell micelles, which were converted into ellipsoidal onion‐like micelles on mixing with the PEO₄₅‐block‐P(DMAEMA₈‐co‐MMA₄) diblock. Onion‐like micelles were crosslinked by quaternization of DMAEMA units. CONCLUSION: Formation of onion‐like micelles by mixing two different AB (ABA) and B′C block copolymers and their subsequent crosslinking is a valuable approach towards stabilized supramolecular assemblies of a higher complexity and functionality than the individual constitutive components. Copyright © 2008 Society of Chemical Industry     

Synthesis of Y‐shaped poly(N,N‐dimethylamino‐2‐ethyl methacrylate) and poly(trimethylene carbonate) from a new heterofunctional initiator

A new amphiphilic Y‐shaped copolymer, comprised of hydrophobic Poly(trimethylene carbonate) (PTMC) and hydrophilic Poly(N,N‐dimethylamino‐2‐ethyl methacrylate) (PDMAEMA), was designed and synthesized by a combination of atom transfer radical polymerization (ATRP) and ring‐opening polymerization (ROP) using a new heterofunctional initiator, Br‐Init‐(OH)₂, bearing one initiation site for ATRP and two for ROP. At first, a new trifunctional core molecule bearing hydroxyl group and bromine moieties, Br‐Init‐(OH)₂, was synthesized via protection followed by esterification reaction of 5‐ethyl‐5‐hydroxymethyl‐2,2‐dimethyl‐1,3‐dioxane with 2‐bromoisobutyryl bromide and deprotection. In the presence of trifunctional core molecule, Br‐Init‐(OH)₂, target Y‐shaped miktoarm star copolymers, (PTMC)₂‐ b‐PDMAEMA, were successfully synthesized by sequence conducting the ROP of TMC and ATRP of DMAEMA. The Y‐shaped copolymers were characterized by ¹H NMR and GPC measurements. Subsequently, the self‐assembly behavior of these copolymers was investigated by dynamic light scattering method and transmission electron microscopy, which indicated that these amphiphilic Y‐shaped copolymers can self‐assemble into micelles and possess distinct pH‐dependent size in aqueous milieu. The results indicate that the amphiphilic Y‐shaped copolymers had the pH‐responsive properties similar to the expected PDMAEMA. POLYM. ENG. SCI., 2011. © 2011 Society of Plastics Engineers     

Poly(methyl methacrylate)/poly(ethylene glycol)/poly(ethylene glycol dimethacrylate) micelles: Preparation,characterization, and application as doxorubicin carriers

A crosslinked amphiphilic copolymer [poly(ethylene glycol) (PEG)–poly(methyl methacrylate) (PMMA)–ethylene glycol dimethacrylate (EGDM)] composed of PMMA, PEG, and crosslinking units (EGDM) was synthesized by atom transfer radical polymerization to develop micelles as carriers for hydrophobic drugs. By adjusting the molar ratio of methyl methacrylate and EGDM, three block copolymer samples (P0, P1, and P2) were prepared. The measurement of gel permeation chromatography and ¹H‐NMR indicated the formation of crosslinked structures for P1 and P2. Fluorescence spectroscopy measurement indicated that PEG–PMMA–EGDM could self‐assemble to form micelles, and the critical micelle concentration values of the crosslinked polymer were lower than those of linear ones. The prepared PEG–PMMA–EGDM micelles were used to load doxorubicin (DOX). The drug‐loading efficiencies of P1 and P2 were higher than that of P0 because the crosslinking units enhanced the micelles' stability. With increasing drug‐loading contents, DOX release from the micelles in vitro was decreased, and in the crosslinked formulations, the release rate was also slower. An in vitro release study indicated that DOX release from the micelles for the linear samples was faster than that for crosslinked micelles. The drug feeding amount increased and resulted in an increase in the drug‐loading content, and the loading efficiency decreased. These PEG–PMMA–EGDM micelles did not show toxicity in vitro and could reduce the cytotoxicity of DOX in the micelles; this suggested that they are good candidates as stable drug carriers. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39623.