Redox‐Responsive Micelles with Cores Crosslinked via Click Chemistry

Redox‐responsive micelles with cores crosslinked via click chemistry are developed to improve the stability of polymer micelles. Amphiphilic block copolymer mPEG‐b‐P(DTC‐ADTC) with pendant azido groups on the hydrophobic chains is synthesized by the ring‐opening polymerization of 2,2‐bis(azidomethyl)trimethylene carbonate (ADTC) and 2,2‐dimethyltrimethylene carbonate (DTC) with monomethoxy poly(ethylene glycol) (mPEG) as an initiator. mPEG‐b‐P(DTC‐ADTC) self‐assemble to form the micelles in aqueous solution and the cores of the micelles are crosslinked via click chemistry to afford redox‐responsive core‐crosslinked micelles. Core‐crosslinking enhances the stability of the micelles in aqueous solution and improve the drug‐loading property. The redox‐responsive core‐crosslinked micelles can be reduced by the addition of reducing agents such as dithiothreitol (DTT), and thus release the loaded drug quickly in the presence of DTT.

     

Amphiphilic Block‐Graft Copolymers with a Degradable Backbone and Polyethylene Glycol Pendant Chains Prepared via Ring‐Opening Polymerization of a Macromonomer

Well‐defined amphiphilic block‐graft copolymers PCL‐b‐[DTC‐co‐(MTC‐mPEG)] with polyethylene glycol methyl ether pendant chains were designed and synthesized. First, monohydroxyl‐terminated macroinitiators PCL‐OH were prepared. Then, ring‐opening copolymerization of 2,2‐dimethyltrimethylene carbonate (DTC) and cyclic carbonate‐terminated PEG (MTC‐mPEG) macromonomer was carried out in the presence of the macroinitiator in bulk to give the target copolymers. All the polymers were characterized by ¹H NMR and gel permeation chromatography (GPC). The polymers have unimodal molecular weight distributions and moderate polydispersity indexes. The amphiphilic block‐graft copolymers self‐assemble in water forming stable micelle solutions with a narrow size distribution.

     

Synthesis and characterization of temperature‐sensitive block‐graft PNiPAAm‐b‐(PαN3CL‐g‐alkyne) copolymers by ring‐opening polymerization and click reaction

This study synthesized thermo‐sensitive amphiphilic block‐graft PNiPAAm‐b‐(PαN₃CL‐g‐alkyne) copolymers through ring‐opening polymerization of α‐chloro‐ε‐caprolactone (αClCL) with hydroxyl‐terminated macroinitiator poly(N‐isopropylacrylamide) (PNiPAAm), substituting pendent chlorides with sodium azide. This was then used to graft various kinds of terminal alkynes moieties by means of the copper‐catalyzed Huisgen's 1,3‐dipolar cycloaddition (“click” reaction). ¹H NMR, FTIR, and gel permeation chromatography (GPC) was used to characterize these copolymers. The solubility of the block‐graft copolymers in aqueous media was investigated using turbidity measurement, revealing a lower critical solution temperature (LCST) in the polymers. These solutions showed reversible changes in optical properties: transparent below the LCST, and opaque above the LCST. The LCST values were dependant on the composition of the polymer. With critical micelle concentrations (CMCs) in the range of 2.04–9.77 mg L^?1, the block copolymers formed micelles in the aqueous phase, owing to their amphiphilic characteristics. An increase in the length of hydrophobic segments or a decrease in the length of hydrophilic segments amphiphilic block‐graft copolymers produced lower CMC values. The research verified the core‐shell structure of micelles by ¹H NMR analyses in D₂O. Transmission electron microscopy was used to analyze the morphology of the micelles, revealing a spherical structure. The average size of the micelles was in the range of 75–145 nm (blank), and 105–190 nm (with drug). High drug entrapment efficiency and drug loading content were observed in the drug micelles. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Lactic acid‐ and carbonate‐based crosslinked polymeric micelles for drug delivery

Our objective was to synthesize and evaluate lactic acid‐ and carbonate‐based biodegradable core‐ and core‐corona crosslinkable copolymers for anticancer drug delivery. Methoxy poly(ethylene glycol)‐b‐poly(carbonate‐co‐lactide‐co‐5‐methyl‐5‐allyloxycarbonyl‐1,3‐dioxane‐2‐one) [mPEG‐b‐P(CB‐co‐LA‐co‐MAC)] and methoxy poly(ethylene glycol)‐b‐poly(acryloyl carbonate)‐b‐poly(carbonate‐co‐lactide) [mPEG‐b‐PMAC‐b‐P(CB‐co‐LA)] copolymers were synthesized by ring‐opening polymerization of LA, CB, and MAC using mPEG as an macroinitiator and 1,8‐diazabicycloundec‐7‐ene as a catalyst. These amphiphilic copolymers which exhibited low polydispersity and critical micelle concentration values (0.8–1 mg/L) were used to prepare micelles with or without drug and stabilized by crosslinking via radical polymerization of double bonds introduced in the core and interface to improve stability. mPEG₁₁₄‐b‐P(CB₈‐co‐LA₃₅‐co‐MAC_2.5) had a higher drug encapsulation efficiency (78.72% ± 0.15%) compared to mPEG₁₁₄‐b‐PMAC_2.5‐b‐P(CB₉‐co‐LA₃₉) (20.29% ± 0.11%).¹H NMR and IR spectroscopy confirmed successful crosslinking (～70%) while light scattering and transmission electron microscopy were used to determine micelle size and morphology. Crosslinked micelles demonstrated enhanced stability against extensive dilution with aqueous solvents and in the presence of physiological simulating serum concentration. Furthermore, bicalutamide‐loaded crosslinked micelles were more potent compared to non‐crosslinked micelles in inhibiting LNCaP cell proliferation irrespective of polymer type. Finally, these results suggest crosslinked micelles to be promising drug delivery vehicles for chemotherapy. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013     

Y‐shaped poly(ethylene glycol) and poly(trimethylene carbonate) amphiphilic copolymer: Synthesis and for drug delivery

New Y‐shaped (AB₂‐type) amphiphilic copolymers of poly(ethylene glycol) (PEG) with poly(trimethylene carbonate) (PTMC), PEG‐b‐(PTMC)₂, were successfully synthesized by the ring‐opening polymerization (ROP) of TMC with bishydroxy‐modified monomethoxy‐PEG (mPEG). First, a bishydroxy functional ROP initiator was synthesized by esterification of acryloyl bromide with mPEG, followed by Michael addition using excess diethanolamine. A series of Y‐shaped amphiphilic PEG‐(PTMC)₂ block copolymers were obtained via ROP of TMC using this PEG with bishydroxyl end groups as macroinitiator and ZnEt₂ as catalyst. The amphiphilic block copolymers with different compositions were characterized by gel permeation chromatography (GPC) and ¹H NMR, and their molecular weight was measured by GPC. The results showed that the molecular weight of Y‐shaped copolymers increased with the increase of the molar ratio of TMC to mPEG‐(OH)₂ initiator in feed while the PEG chain length was kept constant. The Y‐shaped copolymer mPEG‐(PTMC)₂ could self‐assemble into micelles in aqueous medium and the critical micelle concentration values of the micelles decrease with increase in hydrophobic PTMC block length of mPEG‐(PTMC)₂. The in vitro cytotoxicity and controlled drug release properties of the Y‐shaped amphiphilic block copolymers were also investigated. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 8131–8140, 2008     

Synthesis and characterization of amphiphilic block–graft MPEG‐b‐(PαN3CL‐g‐alkyne) degradable copolymers by ring‐opening polymerization and click chemistry

A straightforward strategy is proposed for the synthesis of novel, amphiphilic block–graft MPEG‐b‐(PαN₃CL‐g‐alkyne) degradable copolymers. First, the ring‐opening polymerization of α‐chloro‐ε‐caprolactone (αClCL) was initiated by hydroxy‐terminated macroinitiator monomethoxy poly(ethylene glycol) (MPEG) with SnOct₂ as the catalyst. In a second step, pendent chlorides were converted into azides by the reaction with sodium azide. Finally, various kinds of terminal alkynes were reacted with pendent azides by copper‐catalyzed Huisgen's 1,3‐dipolar cycloaddition, and thus a “click” reaction. These copolymers were characterized by differential scanning calorimetry (DSC), ¹H NMR, IR, and gel permeation chromatography. By fixing the length of the MPEG block and increasing the length of PαClCL (or PαN₃CL) block, an increase tendency in T_gs was observed. However, the copolymers of MPEG‐b‐PαClCL and MPEG‐b‐PαN₃CL were semicrystalline when the M_n of MPEG was above 2000 g mol^?1. The block–graft copolymers formed micelles in the aqueous phase with critical micelle concentrations (CMCs) in the range of 1.4–12.0 mg L^?1 depending on the composition of polymers. The lengths of hydrophilic segment influence the shape of the micelle. The mean hydrodynamic diameters of the micelles from dynamic light scattering were in the range of 90–160 nm. In vitro hydrolytic degradation of block–graft copolymers is faster than the corresponding block copolymers. The drug entrapment efficiency and the drug loading content of micelles depending on the composition of block–graft polymers were described. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 4320–4331, 2008     

Synthesis,self‐assembly,and thermosensitive properties of ethyl cellulose‐g‐P(PEGMA) amphiphilic copolymers

Ethyl cellulose graft poly(poly(ethylene glycol) methyl ether methacrylate) (EC‐g‐P(PEGMA)) amphiphilic copolymers were synthesized via atom transfer radical polymerization (ATRP) and characterized by FTIR, ¹H NMR, and gel permeation chromatography. Reaction kinetics analysis indicated that the graft copolymerization is living and controllable. The self‐assembly and thermosensitive property of the obtained EC‐g‐P(PEGMA) amphiphilic copolymers in water were investigated by dynamic light scattering, transmission electron microscopy, and transmittance. It was found that the EC‐g‐P(PEGMA) amphiphilic copolymers can self‐assemble into spherical micelles in water. The size of the micelles increases with the increase of the side chain length. The spherical micelles show thermosensitive properties with a lower critical solution temperature around 65 °C, which almost independent on the graft density and the length of the side chains. The obtained EC‐g‐P(PEGMA) graft copolymers have both the unique properties of poly(ethylene glycol) and cellulose, which may have the potential applications in biomedicine and biotechnology. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 46: 6907–6915, 2008     

pH‐ and β‐cyclodextrin‐responsive micelles based on polyaspartamide derivatives as drug carrier

A novel kind of graft polymer poly(aspartic acid)‐ethanediamine‐g‐adamantane/methyloxy polyethylene glycol (Pasp‐EDA‐g‐Ad/mPEG) was designed and synthesized for drug delivery in this study. The chemical structure of the prepared polymer was confirmed by proton NMR. The obtained polymer can self‐assemble into micelles which were stable under a physiological environment and displayed pH‐ and β‐cyclodextrin (β‐CD)‐responsive behaviors because of the acid‐labile benzoic imine linkage and hydrophobic adamantine groups in the side chains of the polymer. The doxorubicin (Dox)‐loaded micelles showed a slow release under physiological conditions and a rapid release after exposure to weakly acidic or β‐CD environment. The in vitro cytotoxicity results suggested that the polymer was good at biocompatibility and could remain Dox biologically active. Hence, the Pasp‐EDA‐g‐Ad/mPEG micelles may be applied as promising controlled drug delivery system for hydrophobic antitumor drugs. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 1387–1395     

Complex,degradable polyester materials via ketoxime ether‐based functionalization: Amphiphilic,multifunctional graft copolymers and their resulting solution‐state aggregates

Degradable, amphiphilic graft copolymers of poly(ε‐caprolactone)‐graft‐poly(ethylene oxide), PCL‐g‐PEO, were synthesized via a grafting onto strategy taking advantage of the ketones presented along the backbone of the statistical copolymer poly(ε‐caprolactone)‐co‐(2‐oxepane‐1,5‐dione), (PCL‐co‐OPD). Through the formation of stable ketoxime ether linkages, 3 kDa PEO grafts and p‐methoxybenzyl side chains were incorporated onto the polyester backbone with a high degree of fidelity and efficiency, as verified by NMR spectroscopies and GPC analysis (90% grafting efficiency in some cases). The resulting block graft copolymers displayed significant thermal differences, specifically a depression in the observed melting transition temperature, T_m, in comparison with the parent PCL and PEO polymers. These amphiphilic block graft copolymers undergo self‐assembly in aqueous solution with the P(CL‐co‐OPD‐co‐(OPD‐g‐PEO)) polymer forming spherical micelles and a P(CL‐co‐OPD‐co‐(OPD‐g‐PEO)‐co‐(OPD‐g‐pMeOBn)) forming cylindrical or rod‐like micelles, as observed by transmission electron microscopy and atomic force microscopy. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3553–3563, 2010     

Gas‐forming poly(ethylene glycol)‐b‐poly(L‐lactic acid) micelles

In this study, a novel drug‐carrying micelle composed of methoxy poly(ethylene glycol) (mPEG)‐b‐poly(L‐lactic acid) (PLLA) with gas‐forming carbonate linkage was fabricated. Here, the gas‐forming carbonate linkage was formed by the chemical coupling of the terminal hydroxyl group of the PLLA block and benzyl chloroformate (BC). mPEG‐b‐PLLA‐BC was self‐organized in aqueous solution: the PEG block on the hydrophilic outer shell and the PLLA‐BC block in the hydrophoboic innor core. The cleavage of carbonate linkage by hydrolysis and formation of carbon dioxide nanobubbles in the micellar core enabled an accelerated release of the encapsulated anticancer drug (doxorubicin: DOX) from the mPEG‐b‐PLLA‐BC micelles. The amount of drug (DOX) released from the mPEG‐b‐PLLA‐BC micelle was higher than that from the conventional mPEG‐b‐PLLA micelle, which allowed for increased in vitro toxicity against KB tumor cells. Copyright © 2013 John Wiley & Sons, Ltd.     

Biocompatible and pH‐responsive triblock copolymer mPEG‐b‐PCL‐b‐PDMAEMA: Synthesis,self‐assembly,and application

A series of well‐defined amphiphilic triblock copolymers [polyethylene glycol monomethyl ether]‐block‐poly(ε‐caprolactone)‐block‐poly[2‐(dimethylamino)ethyl methacrylate] (mPEG‐b‐PCL‐b‐PDMAEMA or abbreviated as mPEG‐b‐PCL‐b‐PDMA) were prepared by a combination of ring‐opening polymerization and atom transfer radical polymerization. The chemical structures and compositions of these copolymers have been characterized by Fourier transform infrared spectroscopy, ¹H NMR, and thermogravimetric analysis. The molecular weights of the triblock copolymers were obtained by calculating from ¹H NMR spectra and gel permeation chromatography measurements. Subsequently, the self‐assembly behavior of these copolymers was investigated by fluorescence probe method and transmission electron microscopy, which indicated that these amphiphilic triblock copolymers possess distinct pH‐dependent critical aggregation concentrations and can self‐assemble into micelles or vesicles in PBS buffer solution, depending on the length of PDMA in the copolymer. Agarose gel retardation assays demonstrated that these cationic nanoparticles can effectively condense plasmid DNA. Cell toxicity tests indicated that these triblock copolymers displayed lower cytotoxicity than that of branched polyethylenimine with molecular weight of 25 kDa. In addition, in vitro release of Naproxen from these nanoparticles in pH buffer solutions was conducted, demonstrating that higher PCL content would result in the higher drug loading content and lower release rate. These biodegradable and biocompatible cationic copolymers have potential applications in drug and gene delivery. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 1079–1091, 2010     

Amphiphilic PEG‐grafted poly(ester‐carbonate)s: Synthesis and diverse nanostructures in water

Novel biodegradable amphiphilic graft copolymers containing hydrophobic poly(ester‐carbonate) backbone and hydrophilic poly(ethylene glycol) (PEG) side chains were synthesized by a combination of ring‐opening polymerization and “click” chemistry. First, the ring‐opening copolymerization of 5,5‐dibromomethyl trimethylene carbonate (DBTC) and ε‐caprolactone (CL) was performed in the presence of stannous octanoate [Sn(Oct)₂] as catalyst, resulting in poly(DBTC‐co‐CL) with pendant bromo groups. Then the pendant bromo groups were completely converted into azide form, which permitted “click” reaction with alkyne‐terminated PEG by Huisgen 1,3‐dipolar cycloadditions to give amphiphilic biodegradable graft copolymers. The graft copolymers were characterized by proton nuclear magnetic resonance (¹H NMR), Fourier transform infrared spectra and gel permeation chromatography measurements, which confirmed the well‐defined graft architecture. These copolymers could self‐assemble into micelles in aqueous solution. The size and morphologies of the copolymer micelles were measured by transmission electron microscopy and dynamic light scattering, which are influenced by the length of PEG and grafting density. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011.     

Amphiphilic diblock copolymers based on poly(2‐ethyl‐2‐oxazoline) and poly(4‐substituted‐ε‐caprolactone): Synthesis,characterization, and cellular uptake

Amphiphilic diblock copolymers with various block compositions were synthesized on poly(2‐ethyl‐2‐oxazoline) (PEtOz) as a hydrophilic block and poly(4‐methyl‐ε‐caprolactone) (PMCL) or poly(4‐phenyl‐ε‐caprolactone) (PBCL) as a hydrophobic block. These PEtOz‐b‐PMCL and PEtOz‐b‐PBCL copolymers consisting of soft domains of amorphous PEtOz and PM(B)CL had no melting endothermal peaks but displayed T_g. The lower critical solution temperature (LCST) values for the PEtOz‐b‐PMCL, and the PEtOz‐b‐PBCL aqueous solution were observed to shift to lower temperature than PEtOz homopolymers. Their aqueous solutions were characterized using fluorescence techniques and dynamic light scattering (DLS). The block copolymers formed micelles with critical micelle concentrations (CMCs) in the range 0.6–11.1 mg L^?1 in an aqueous phase. As the length of the hydrophobic PMCL or PBCL blocks elongated, lower CMC values were generated. The mean diameters of the micelles were between 127 and 318 nm, with PDI in the range of 0.06–0.21, suggesting nearly monodisperse size distributions. The drug entrapment efficiency and drug‐loading content of micelles depend on block polymer compositions. In vitro cell viability assay showed that PEtOz‐b‐PMCL has low cytotoxicity. Doxorubicin hydrochloride (DOX)‐loaded micelles facilitated human cervical cancer (HeLa) cell uptake of DOX; uptake was completed within 2 h, and DOX was able to reach intracellular compartments and enter the nuclei by endocytosis. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 2769–2781     

ATNRC and SET‐NRC synthesis of PtBA‐g‐PEO well‐defined amphiphilic graft copolymers

A series of new well‐defined amphiphilic graft copolymers containing hydrophobic poly(tert‐butyl acrylate) backbone and hydrophilic poly(ethylene oxide) side chains were reported. Reversible addition‐fragmentation chain transfer homopolymerization of tert‐butyl 2‐((2‐bromopropanoyloxy)methyl)acrylate was first performed to afford a well‐defined backbone with a narrow molecular weight distribution (M_w/M_n = 1.07). The target poly(tert‐butyl acrylate)‐g‐poly(ethylene oxide) (PtBA‐g‐PEO) graft copolymers with low polydispersities (M_w/M_n = 1.18–1.26) were then synthesized by atom transfer nitroxide radical coupling or single electron transfer‐nitroxide radical coupling reaction using CuBr(Cu)/PMDETA as catalytic system. Fluorescence probe technique was employed to determine the critical micelle concentrations (cmc) of the obtained amphiphilic graft copolymers in aqueous media. Furthermore, PAA‐g‐PEO graft copolymers were obtained by selective acidic hydrolysis of hydrophobic PtBA backbone while PEO side chains kept inert. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Synthesis and pH‐responsive assembly of methoxy poly(ethylene glycol)‐b‐poly(ε‐caprolactone) with pendant carboxyl groups

pH‐responsive methoxy poly(ethylene glycol)‐b‐poly(ε‐caprolactone) bearing pendant carboxyl groups mPEG‐b‐P(2‐CCL‐co‐6‐CCL) was synthesized based on our newly monomer benzyloxycarbonylmethly functionalized ε‐caprolactone. Their structure was confirmed by ¹H NMR, ¹³C NMR, and Fourier transform infrared spectrum spectra. In addition, SEC results indicated that the copolymers had a relatively narrow polydispersity. WXRD and DSC demonstrated that the introduction of carboxymethyl groups had significant effect on the crystallinity of the copolymers. Furthermore, the solution behavior of mPEG‐b‐P(2‐CCL‐co‐6‐CCL) has been studied by various methods. The results indicated that mPEG‐b‐P(2‐CCL‐co‐6‐CCL) had a rich pH‐responsive behavior and the micelles could be formed by pH induction, and the mPEG‐b‐P(2‐CCL‐co‐6‐CCL) could existed as unimers, micelles or large aggregates in different pH range accordingly. The mechanism of which was supposed to depend on the counteraction between the hydrophobic interaction from PCL and the ionization of the carboxyl groups along the polymer chain. Moreover, the mPEG‐b‐P(2‐CCL‐co‐6‐CCL) copolymers displayed good biocompatibility according to the preliminary cytotoxicity study. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 188–199     

Biocompatible poly(ethylene glycol)‐poly(γ‐cholesterol‐L‐glutamate) copolymers: Synthesis,characterization, and in vitro studies

A novel amphiphilic poly(ethylene glycol)‐block‐poly(γ‐cholesterol‐L ‐glutamate) (mPEG–PCHLG) diblock copolymer has been synthesized. The mPEG–PCHLG copolymer has good biocompatibility and low toxicity. The mPEG–PCHLG copolymers could aggregate into nanoparticles with PCHLG blocks as the hydrophobic core and PEG blocks as the hydrophilic shell through emulsion solvent evaporation method. The copolymers were characterized by nuclear magnetic resonance spectroscopy, mass spectrum, Fourier transform infrared spectroscopy, and gel permeation chromatography. The particle sizes, size distributions, and zeta potentials of nanoparticles can also be determined by dynamic light scattering and transmission electron microscopy. This work provides a new and facile approach to prepare amphiphilic block copolymer nanoparticles with controllable performances. This novel copolymer may have potential applications in drug delivery and bioimaging applications.© 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Successive SET‐LRP and ATRP synthesis of ferrocene‐based PPEGMEA‐g‐PAEFC well‐defined amphiphilic graft copolymer

A series of ferrocene‐based well‐defined amphiphilic graft copolymers, consisting of hydrophilic poly[poly(ethylene glycol) methyl ether acrylate] (PPEGMEA) backbone and hydrophobic poly(2‐acryloyloxyethyl ferrocenecarboxylate) (PAEFC) side chains were synthesized by successive single‐electron‐transfer living radical polymerization (SET‐LRP) and atom transfer radical polymerization (ATRP). The backbone was prepared by SET‐LRP of PEGMEA macromonomer, and it was then treated with lithium di‐isopropylamide and 2‐bromopropionyl bromide at ?78 °C to give PPEGMEA‐Br macroinitiator. The targeted well‐defined graft copolymers with narrow molecular weight distributions (M_w/M_n ≤ 1.32) were synthesized via ATRP of AEFC initiated by PPEGMEA‐Br macroinitiator, and the molecular weights of the backbone and side chains were both controllable. The electro‐chemical behaviors of graft copolymers were studied by cyclic voltammetry, and it was found that graft copolymers were more difficult to be oxidized, and the reversibility of electrode process became less with raising the content of PAEFC segment. The effects of the preparation method, the length of hydrophobic PAEFC segment, and the initial water content on self‐assembly behavior of PPEGMEA‐g‐PAEFC graft copolymers in aqueous media were investigated by transmission electron microscopy. The morphologies of micelles could transform from cylinders to spheres or rods with changing the preparation condition and the length of side chains. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Synthesis and characterization of amphiphilic block copolymers with allyl side‐groups

The synthesis of a new cyclic carbonate monomer containing an allyl group was reported and its biodegradable amphiphilic block copolymer, poly(ethylene glycol)‐block‐poly(L ‐lactide‐co‐5‐methyl‐5‐allyloxycarbonyl‐propylene carbonate) [PEG‐b‐P(LA‐co‐MAC)] was synthesized by ring‐opening polymerization (ROP) of L ‐lactide (LA) and 5‐methyl‐5‐allyloxycarbonyl‐1,3‐dioxan‐2‐one (MAC) in the presence of poly (ethylene glycol) as a macroinitiator, with diethyl zinc as a catalyst. ¹³C NMR and ¹H NMR were used for microstructure identification of the copolymers. The copolymer could form micelles in aqueous solution. The core of the micelles is built of the hydrophobic P(LA‐co‐MAC) chains, whereas the shell is set up by the hydrophilic PEG blocks. The micelles exhibited a homogeneous spherical morphology and unimodal size distribution. By using the cyclic carbonate monomer containing allyl side‐groups, crosslinking of the PEG‐b‐P(LA‐co‐MAC) inner core was possible. The adhesion and spreading of ECV‐304 cells on the copolymer were better than that on PLA films. Therefore, this biodegradable amphiphilic block copolymer is expected to be used as a biomaterial for drug delivery and tissue engineering. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5518–5528, 2007     

Photoresponsive biodegradable poly(carbonate)s with pendent o‐nitrobenzyl ester

Photoresponsive amphiphilic diblock poly(carbonate)s mPEG₁₁₃‐b‐PMNC_n with pendent o‐nitrobenzyl ester group were synthesized through ring‐opening polymerization (ROP) using 1,8‐diazabi‐cyclo[5.4.0]undec‐7‐ene (DBU) as catalyst and monomethoxy poly(ethylene glycol) (mPEG) as macroinitiator. In aqueous solution, the copolymers can self‐assemble to spherical micelles with a PC core and a PEG shell. The critical micelle concentration (CMC), size, and morphology of the micelles were demonstrated by means of fluorescence spectroscopy, transmission electron microscopes (TEM), and dynamic light scattering (DLS). Under UV light irradiation, the amphiphilic copolymer micelles disassembled because of the photocleavage of o‐NB ester, and the light‐controlled release behaviors of payload Nile red were further proved. This study provides a convenient way to construct smart poly(carbonate)s nanocarriers for controlled drug release. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 2770–2780     

Preparation of main‐chain imidazolium‐functionalized amphiphilic block copolymers through combination of condensation polymerization and nitroxide‐mediated free radical polymerization and their micelle study

Main‐chain imidazolium‐functionalized amphiphilic block copolymers (PIL‐b‐PS) consisting of polyionic liquid (PIL) and polystyrene (PS) blocks have been first synthesized by condensation polymerization combined with nitroxide‐mediated free radical polymerization (NMP). The di‐functional imidazolium‐based ionic liquid (IL) having both hydroxyl and ester end groups was synthesized through Michael addition between imidazole and methylacrylate (MA) and further quaternization by 2‐chloroethanol. The HTEMPO (4‐hydroxy‐2,2,6,6‐tetramethyl‐1‐piperidinyloxy) terminated polyionic liquid (HTEMPO‐PIL) as the hydrophilic block was prepared by condensation polymerization of di‐functional imidazolium IL and HTEMPO at a certain ratio. The hydrophobic PS block was synthesized by controlled radical polymerization of styrene using HTEMPO‐PIL through NMP, resulting PIL‐b‐PS block copolymers. The structure of block copolymers obtained has been characterized and verified by FTIR, ¹H NMR, and size exclusion chromatography analyses. In addition, the morphology and size of the micelles formed by PIL‐b‐PS block copolymers in water were investigated by transmission electron microscopy and dynamic light scattering. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012