Formation of polymeric micelles with amino surfaces from amphiphilic AB‐type diblock copolymers composed of poly(glycolic acid lysine) segments and polylactide segments

Amphiphilic AB‐type diblock copolymers composed of hydrophobic poly(L ‐lactide) (PLA) segments and hydrophilic poly(glycolic acid lysine) [poly(Glc‐Lys)] segments with amino side‐chain groups self‐associated to form PLA‐based polymeric micelles with amino surfaces in an aqueous solution. The average diameter of the loose core–shell polymeric micelles for poly(Glc‐Lys) [number‐average molecular weight (M_n) = 1240]‐b‐PLA (M_n = 7000) obtained by a dimethyl sulfoxide/water dialysis method was estimated to be about 50 nm in water by dynamic light scattering measurements. The size and shape of the obtained polymeric micelles were further observed with transmission electron microscopy and atomic force microscopy. To investigate the possibility of applying the obtained PLA‐based polymeric micelles as bioabsorbable vehicles for hydrophobic drugs, we tested the entrapment of drugs in poly(Glc‐Lys) (M_n = 1240)‐b‐PLA (M_n = 7000) micelles and their release with doxorubicin as a hydrophobic drug. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 1426–1432, 2002     

Size and morphology controllable core cross‐linked self‐aggregates from poly(ethylene glycol‐b‐succinimide) copolymers

We developed a simple route to prepare stabilized micelles and nanovesicles in aqueous solutions. A hydrophobic poly(succinimide) (PSI) was conjugated with the hydrophilic poly(ethylene glycol) (PEG) as a new type of cross‐linkable unit. Spherical aggregates were formed when dissolving the amphiphilic PEG₆₈₂‐b‐PSI₁₃₀ copolymer in aqueous solutions directly, and polymer nanovesicles were prepared by a precipitation‐dialysis method using PEG₄₅₅‐b‐PSI₁₃₀ copolymer. Bifunctional primary amine was added to the micelle or nanovesicle solutions to prepare cross‐linked structures via aminolysis reaction of the succinimide units. The degree of cross‐linking was controlled by adjusting the molar ratio of the cross‐linker to the succinimide units. Increasing the degree of cross‐linking leads to the compaction of the micelle core thus reduced diameter. The cross‐linked polymer micelles or nanovesicles maintained their morphology in extremely diluted solutions because of their structural stability. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

Construction of temperature responsive hybrid crosslinked self‐assemblies based on PEG‐b‐P(MMA‐co‐MPMA)‐b‐PNIPAAm triblock copolymer: ATRP synthesis and thermoinduced association behavior

A novel amphiphilic thermosensitive poly(ethylene glycol)₄₅‐b‐poly(methyl methacrylate₄₆‐co‐3‐(trimethoxysilyl)propyl methacrylate)₂‐b‐poly(N‐isopropylacrylamide)₄₂₉ (PEG₄₅‐b‐P(MMA₄₆‐co‐MPMA₂)‐b‐PNIPAAm₄₂₉) triblock copolymer was synthesized via consecutive atom transfer radical polymerization techniques. The thermoinduced association behavior of the resulting triblock copolymers in aqueous medium was further investigated in detail by ¹H NMR, transmission electron microscopy, and dynamic light scattering. The results showed that at the temperature (25 °C) below the LCST, PEG₄₅‐b‐P(MMA₄₆‐co‐MPMA₂)‐b‐PNIPAAm₄₂₉ triblock copolymers self‐assembled into the core crosslinked micelles with the hydrophobic P(MMA‐co‐MPMA) block constructing a dense core, protected by the mixed soluble PEG and PNIPAAm chains acting as a hydrophilic shell simultaneously. With an increase in temperature, the resulting core‐shell micelles converted into a new type of micelles with the hydrophilic PEG chains stretching out from the hydrophobic core through the collapsed PNIPAAm shell. On the other hand, at the temperature (40 °C) above the LCST, such triblock copolymers formed the crosslinked vesicles with the hydrophobic PNIPAAm and P(MMA‐co‐MPMA) blocks constructing a membrane core and the soluble PEG chains building the hydrophilic lumen and the shell. On further decreasing the temperature, the resulting vesicles underwent transformation from the shrunken to the expanded status, leading to the formation of swollen vesicles with enlarged size. This study is believed to present the first formation of two types of hybrid crosslinked self‐assemblies by thermoinduced regulation. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

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     

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     

RAFT synthesis of polystyrene‐block‐poly(polyethylene glycol monomethyl ether acrylate) for zinc phthalocyanine‐loaded polymeric micelles as photodynamic therapy photosensitizers

A series of polystyrene‐block‐poly(polyethylene glycol monomethyl ether acrylate) (PSt_m‐b‐PPEGA_n) polymers were systematically synthesized as carriers for zinc phthalocyanine (ZnPc) for photodynamic therapy via reversible addition and fragmentation chain transfer polymerization. The degree of polymerization of the styrene (m) and PEGA units (n) of the resulting block copolymers were characterized to be n = 174, 40, and 18 for m = 52; and n = 200, 84, and 31 for m = 30. All the block copolymers formed micelles in water. The critical micelle concentration (CMC) of the PSt_m‐b‐PPEGA_n was determined by fluorometry using pyrene as a hydrophobic probe. The CMC value increased from 4.5 to 20 mg·L⁻¹ with an increase in the mole fraction of PEGA units. The median diameters of the micelles increased from 19 to 31 nm for PSt₅₂‐b‐PPEGA_n and from 15 to 23 nm for PSt₃₀‐b‐PPEGA_n with increasing n value. ZnPc‐loaded micelles were prepared by dialysis of the block copolymer in the presence of ZnPc followed by removal of large aggregates by filtration. The encapsulation efficiency was dramatically changed in the range of 0–68%. The light‐dose‐dependent cytotoxicity of the ZnPc‐loaded PSt₃₀‐b‐PPEGA₂₀₀ was clearly established in HeLa cell lines; while no cytotoxicity was confirmed under the dark. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 560–570     

Well‐defined poly(oxazoline)‐b‐poly(acrylate) amphiphilic copolymers: From synthesis by polymer–polymer coupling to self‐organization in water

In this contribution, we report on the self‐assembly in water of original amphiphilic poly(2‐methyl‐2‐oxazoline)‐b‐poly(tert‐butyl acrylate) copolymers, synthesized by copper‐catalyzed azide–alkyne cycloaddition (CuAAC) reaction. For such purpose, (poly(2‐methyl‐2‐oxazoline)) and (poly(tert‐butyl acrylate)) are first prepared by cationic ring‐opening polymerization and atom transfer radical polymerization, respectively. Well‐defined polymeric building blocks, ω‐N₃‐P(t‐BA) and α‐alkyne‐P(MOx), bearing reactive chain end groups, are accurately characterized by matrix‐assisted laser desorption ionization time‐of‐flight spectroscopy. Then, P(MOx)_n‐b‐P(t‐BA)_m are achieved by polymer–polymer coupling and are fully characterized by diffusion‐ordered NMR spectroscopy and size exclusion chromatography, demonstrating the obtaining of pure amphiphilic copolymers. Consequently, the latter lead to the formation in water of well‐defined monodisperse spherical micelles (R_H = 40–60 nm), which are studied by fluorescence spectroscopy, static light scattering, atomic force microscope, and transmission electronic microscopy. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013     

The glucose‐responsive behavior of a block copolymer featuring boronic acid and glycine

Glucose responsive block copolymer featuring boronic acid as a glucose responsive moiety and glycine are reported. The first block is polymerized through reversible addition–fragmentation chain transfer (RAFT) polymerization and the resulting poly(N‐acryloylmorpholine)₁₁₃ (PAcM) is employed as a macro‐chain transfer agent for chain extension with pentafluorophenyl acrylate (PFPA) yielding a well‐defined PAcM₁₁₃‐block‐poly(pentafluorophenyl acrylate)₈₄ (PPFPA). The PPFPA block is then reacted with functional (3‐aminomethyl) phenyl boronic acid and glycine via post‐polymerization modification and the structure of the block copolymer is confirmed by proton nuclear magnetic resonance (NMR), ¹⁹F NMR, Fourier transform infrared, and gel permeation chromatography. By copolymerizing glycine into the polymer backbone, the relative pK_a of the block copolymer is significantly lowered. The block copolymer can self‐assemble into core–shell micelles in aqueous solution and disassemble in response to glucose at the physiological pH. Furthermore, the encapsulation and release of Nile red (NR) as a hydrophobic model drug is studied under the physiological pH. The influence of the glucose concentration on the NR release from the polymeric micelles is demonstrated. These results suggested that the glucose‐responsive poly[(AcM)₁₁₃‐b‐(3‐(aminomethyl)phenylboronic acid hydrochloride(‐co‐Gly)₈₄] block copolymer has potential applications as a glucose‐responsive polymer for insulin delivery. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019 , 57, 422–431     

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.     

Encapsulation of nanomaterials using an intermediary layer cross‐linkable ABC triblock copolymer

For the preparation of core‐shell nanoparticles containing functional nanomaterials, a photo‐cross‐linkable amphiphilic ABC triblock copolymer, poly(ethylene glycol)‐b‐poly(2‐cinnamoyloxyethyl methacrylate)‐b‐poly(methyl methacrylate) (PEG‐PCEMA‐PMMA), was synthesized. This triblock copolymer was then used to encapsulate Au nanoparticles or pyrene. The triblock copolymer of PEG‐b‐poly(2‐hydroxyethyl methacrylate)‐b‐PMMA (PEG‐PHEMA‐PMMA) (M_n = 15,800 g/mol, M_w/M_n = 1.58) was first synthesized by activators generated by electron transfer atom transfer radical polymerization. Its middle block was then functionalized with cinnamoyl chloride. The degrees of polymerization of the PEG, PHEMA, and PMMA blocks were 45, 13, and 98, respectively. PMMA‐tethered Au nanoparticles (with an average diameter of 3.0 nm) or pyrene was successfully encapsulated within the PEG‐PCEMA‐PMMA micelles. The intermediary layers of the micelles were then cross‐linked by UV irradiation. The spherical structures of the PEG‐PCEMA‐PMMA micelles containing Au nanoparticles or pyrene were not changed by the photo‐cross‐linking process and they showed excellent colloidal stability. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 4963–4970, 2009     

The self‐assembly over nano‐ to submicro‐length scales in water of a fluorescent julolidine‐labeled amphiphilic random terpolymer

A novel fluorescent‐labeled amphiphilic random terpolymer is synthesized by controlled radical polymerization of a fluorescent molecular rotor monomer, 2‐cyano‐2‐[4‐vinyl(1,1′‐biphenyl)‐4′‐yl]vinyljulolidine, a hydrophilic monomer, poly (ethylene glycol) methyl ether methacrylate, and a hydrophobic monomer, perfluorohexylethyl acrylate. Combined dynamic light scattering and fluorescence emission spectroscopy measurements are used to investigate its self‐assembly in water solution. Self‐assembled nanostructures with a hydrodynamic diameter size D_h of 4 ± 1 nm are detected due to the single‐chain folding of the terpolymer in unimer micelles. The fluorescence emission intensity of the terpolymer in water solution is found to be one order of magnitude higher than that in organic solvents, as a result of the preferential encapsulation of the julolidine co‐units in hydrophobic compartments of the unimer micelles. The temperature dependence of the self‐associative behavior of the amphiphilic terpolymer is also investigated and a critical temperature is identified at which a transition between single‐chain unimer micelles and multi‐chain aggregates (D_h = 400 ± 40 nm) reversibly takes place on heating–cooling cycles. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 797–804     

Thermoresponsive star triblock copolymers by combination of ROP and ATRP: From micelles to hydrogels

Novel biocompatible, biodegradable, four‐arm star, triblock copolymers containing a hydrophobic poly(ε‐caprolactone) (PCL) segment, a hydrophilic poly(oligo(ethylene oxide)475 methacrylate) (POEOMA475) segment and a thermoresponsive poly(di(ethylene oxide) methyl ether methacrylate) (PMEO₂MA) segment were synthesized by a combination of controlled ring‐opening polymerization (ROP) and atom transfer radical polymerization (ATRP). First, a four‐arm PCL macroinitiator [(PCL‐Br)₄] for ATRP was synthesized by the ROP of ε‐caprolactone (CL) catalyzed by stannous octoate in the presence of pentaerythritol as the tetrafunctional initiator followed by esterification with 2‐bromoisobutyryl bromide. Then, sequential ATRP of oligo(ethylene oxide) methacrylate (OEOMA475, M_n = 475) and di(ethylene oxide) methyl ether methacrylate) (MEO₂MA) were carried out using the (PCL‐Br)₄ tetrafunctional macroinitiator, in different sequence, resulting in preparation of (PCL‐b‐POEOMA475‐b‐PMEO₂MA)₄ and (PCL‐b‐PMEO₂MA‐b‐POEOMA475)₄ star triblock copolymers. These amphiphilic copolymers can self‐assemble into spherical micelles in aqueous solution at room temperature. The thermal responses of the polymeric micelles were investigated by dynamic light scattering and ultraviolet spectrometer. The properties of the two series of copolymers are quite different and depend on the sequence distribution of each block along the arms of the star. The (PCL‐b‐POEOMA475‐b‐PMEO₂MA)₄ star copolymer, with the thermoresponsive PMEO₂MA segment on the periphery, can undergo reversible sol‐gel transitions between room temperature (22 °C) and human body temperature (37 °C). © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Dimensional Control of Block Copolymer Nanofibers with a π‐Conjugated Core: Crystallization‐Driven Solution Self‐Assembly of Amphiphilic Poly(3‐hexylthiophene)‐b‐poly(2‐vinylpyridine)

With the aim of accessing colloidally stable, fiberlike, π‐conjugated nanostructures of controlled length, we have studied the solution self‐assembly of two asymmetric crystalline–coil, regioregular poly(3‐hexylthiophene)‐b‐poly(2‐vinylpyridine) (P3HT‐b‐P2VP) diblock copolymers, P3HT₂₃‐b‐P2VP₁₁₅ (block ratio=1:5) and P3HT₄₄‐b‐P2VP₁₁₅ (block ratio=ca. 1:3). The self‐assembly studies were performed under a variety of solvent conditions that were selective for the P2VP block. The block copolymers were prepared by using Cu‐catalyzed azide–alkyne cycloaddition reactions of azide‐terminated P2VP and alkyne end‐functionalized P3HT homopolymers. When the block copolymers were self‐assembled in a solution of a 50 % (v/v) mixture of THF (a good solvent for both blocks) and an alcohol (a selective solvent for the P2VP block) by means of the slow evaporation of the common solvent; fiberlike micelles with a P3HT core and a P2VP corona were observed by transmission electron microscopy (TEM). The average lengths of the micelles were found to increase as the length of the hydrocarbon chain increased in the P2VP‐selective alcoholic solvent (MeOH<iPrOH<nBuOH). Very long (>3 μm) fiberlike micelles were prepared by the dialysis of solutions of the block copolymers in THF against iPrOH. Furthermore the widths of the fibers were dependent on the degree of polymerization of the chain‐extended P3HT blocks. The crystallinity and π‐conjugated nature of the P3HT core in the fiberlike micelles was confirmed by a combination of UV/Vis spectroscopy, photoluminescence (PL) measurements, and wide‐angle X‐ray scattering (WAXS). Intense sonication (iPrOH, 1 h, 0 °C) of the fiberlike micelles formed by P3HT₂₃‐b‐P2VP₁₁₅ resulted in small (ca. 25 nm long) stublike fragments that were subsequently used as initiators in seeded growth experiments. Addition of P3HT₂₃‐b‐P2VP₁₁₅ unimers to the seeds allowed the preparation of fiberlike micelles with narrow length distributions (L_w/L_n <1.11) and lengths from about 100‐300 nm, that were dependent on the unimer‐to‐seed micelle ratio.     

Synthesis,self‐assembly,and formation of photo‐crosslinking‐stabilized fluorescent micelles covalently containing zinc(II)‐bis(8‐hydroxyquinoline) for ABC triblock copolymer bearing cinnamoyl and 8‐hydroxyquinoline side groups

Triblock copolymers (MPEG‐b‐PCEMA‐b‐PHQHEMA) bearing cinnamoyl and 8‐hydroxyquinoline side groups with different block length are synthesized by a two‐step reversible addition fragmentation chain transfer polymerization of cinnamoyl ethyl methacrylate (CEMA) and 2‐((8‐hydroxyquinolin‐5‐yl)methoxy)ethyl methacrylate (HQHEMA), respectively. The self‐assembly of MPEG‐b‐PCEMA‐b‐PHQHEMA in mixture of THF and ethanol is investigated by varying the ratio of THF and ethanol. Spheric micelles with diameter of 63.7 nm and polydispersity of 0.128 are obtained for MPEG₁₁₃‐b‐PCEMA₁₅‐b‐PHQHEMA₁₇ in THF/ethanol with a volume ratio (v/v) of 5/5. The PCEMA inner shell of the resulted micelles is photo‐crosslinked under UV radiation to give stabilized micelles. The complex reaction of the stabilized micelles with Zn(II) is investigated under different conditions to give zinc(II)‐bis(8‐hydroxyquinoline)(Znq₂)‐containing micelles. When the complex reaction is carried out in THF/ethanol (v/v = 5/5) or THF/toluene (v/v = 6/4) with zinc acetate, fluorescent Znq₂‐containing micelles are obtained without obvious change in diameters and morphologies. The fluorescent micelles exhibit green emission with λ_max at 520 nm. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 1056–1064     

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     

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     

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     

Molecular Nanoworm with PCL Core and PEO Shell as a Non‐spherical Carrier for Drug Delivery

Core/shell wormlike polymer brushes with densely grafted poly(ϵ‐caprolactone)‐b‐poly(ethylene oxide) (PCL‐b‐PEO) are synthesized via grafting an alkynyl terminated PCL‐b‐PEO (ay‐PCL₁₇‐b‐PEO₁₁₃) onto a well‐defined azido functionalized polymethacrylate (PGA₉₄₀) and are evaluated preliminarily as a single molecular cylindrical vehicle for drug delivery. Water soluble molecular worms of ca. 230 nm are obtained and then the anticancer drug doxorubicin (DOX) is loaded into its PCL core by hydrophobic interaction. Compared with spherical micelles from linear PCL₁₇‐b‐PEO₁₁₃, the brushes demonstrate a lower loading efficiency but a faster release rate of DOX. Confocal laser scanning microscopy measurements show that DOX‐loaded cylindrical molecular brushes can easily enter into HeLa and HepG2 cells in 1 h.     

Fluorine‐containing linear block terpolymers: Synthesis and self‐assembly in solution

Linear triblock terpolymers of poly(n‐butyl methacrylate)‐b‐poly(methyl methacrylate)‐b‐poly(2‐fluoroethyl methacrylate) (PnBMA‐PMMA‐P2FEMA) were synthesized by sequential reversible addition fragmentation chain transfer (RAFT) polymerization. Kinetic studies of the homopolymerization of 2FEMA by RAFT polymerization demonstrated controllable characteristics with fairly narrow polydispersities (～1.30). The resultant PnBMA‐PMMA‐P2FEMA triblock terpolymers were characterized via ¹H NMR, ¹⁹F NMR, and gel permeation chromatography. These polymers formed micellar aggregates in a selective solvent mixture. The as‐formed micelles were analyzed using scanning electron microscopy and dynamic light scattering. It was found that these terpolymers could directly self‐organize into complex micelles in a tetrahydrofuran/methanol mixture with diameters that depended on polymer composition. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011