New Linear and Star‐Shaped Thermogelling Poly([R]‐3‐hydroxybutyrate) Copolymers

The synthesis of multi‐arm poly([R]‐3‐hydroxybutyrate) (PHB)‐based triblock copolymers (poly([R]‐3‐hydroxybutyrate)‐b‐poly(N‐isopropylacrylamide)‐b‐[[poly(methyl ether methacrylate)‐g‐poly(ethylene glycol)]‐co‐[poly(methacrylate)‐g‐poly(propylene glycol)]], PHB‐b‐PNIPAAM‐b‐(PPEGMEMA‐co‐PPPGMA), and their subsequent self‐assembly into thermo‐responsive hydrogels is described. Atom transfer radical polymerization (ATRP) of N‐isopropylacrylamide (NIPAAM) followed by poly(ethylene glycol) methyl ether methacrylate (PEGMEMA) and poly(propylene glycol) methacrylate (PPGMA) was achieved from bromoesterified multi‐arm PHB macroinitiators. The composition of the resulting copolymers was investigated by ¹H and ¹³C J‐MOD NMR spectroscopy as well as size‐exclusion chromatography (SEC), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). The copolymers featuring different architectures and distinct hydrophilic/hydrophobic contents were found to self‐assemble into thermo‐responsive gels in aqueous solution. Rheological studies indicated that the linear one‐arm PHB‐based copolymer tend to form a micellar solution, whereas the two‐ and four‐arm PHB‐based copolymers afforded gels with enhanced mechanical properties and solid‐like behavior. These investigations are the first to correlate the gelation properties to the arm number of a PHB‐based copolymer. All copolymers revealed a double thermo‐responsive behavior due to the NIPAAM and PPGMA blocks, thus allowing first the copolymer self‐assembly at room temperature, and then the delivery of a drug at body temperature (37 °C). The non‐significant toxic response of the gels, as assessed by the cell viability of the CCD‐112CoN human fibroblast cell line with different concentrations of the triblock copolymers ranging from 0.03 to 1 mg mL^?1, suggest that these PHB‐based thermo‐responsive gels are promising candidate biomaterials for drug‐delivery applications.     

Synthesis,self‐assembly,drug‐release behavior,and cytotoxicity of triblock and pentablock copolymers composed of poly(ε‐caprolactone), poly(L‐lactide), and poly(ethylene glycol)

Biocompatible and biodegradable ABC and ABCBA triblock and pentablock copolymers composed of poly(ε‐caprolactone) (PCL), poly(L ‐lactide) (PLA), and poly(ethylene glycol) (PEO) with controlled molecular weights and low polydispersities were synthesized by a click conjugation between alkyne‐terminated PCL‐b‐PLA and azide‐terminated PEO. Their molecular structures, physicochemical and self‐assembly properties were thoroughly characterized by means of FT‐IR, ¹H‐NMR, gel permeation chromatography, differential scanning calorimetry, wide‐angle X‐ray diffraction, dynamic light scattering, and transmission electron microscopy. These copolymers formed microphase‐separated crystalline materials in solid state, where the crystallization of PCL block was greatly restricted by both PEO and PLA blocks. These copolymers self‐assembled into starlike and flowerlike micelles with a spherical morphology, and the micelles were stable over 27 days in aqueous solution at 37 °C. The doxorubicin (DOX) drug‐loaded nanoparticles showed a bigger size with a similar spherical morphology compared to blank nanoparticles, demonstrating a biphasic drug‐release profile in buffer solution and at 37 °C. Moreover, the DOX‐loaded nanoparticles fabricated from the pentablock copolymer sustained a longer drug‐release period (25 days) at pH 7.4 than those of the triblock copolymer. The blank nanoparticles showed good cell viability, whereas the DOX‐loaded nanoparticles killed fewer cells than free DOX, suggesting a controlled drug‐release effect. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

Synthesis,self‐assembly,and thermosensitivity of amphiphilic POEGMA‐PDMS‐POEGMA triblock copolymers

In this article, the synthesis and self‐assembly of a novel well‐defined biocompatible amphiphilic POEGMA‐PDMS‐POEGMA triblock copolymer were studied. The copolymer was synthesized by atom transfer radical polymerization of oligo(ethylene glycol) methyl ether methacrylate (OEGMA) using α,ω‐dibromo polydimethylsiloxane macroinitiator (Br‐PDMS‐Br). Br‐PDMS‐Br was synthesized through the esterification of α,ω‐hydroxypropyl polydimethylsiloxane and 2‐bromoisobutyryl bromide. The structures of the copolymers were confirmed by proton nuclear magnetic resonance spectroscopy, and gel permeation chromatography. The copolymers showed reversible aggregation in response to temperature cycles with a lower critical solution temperature (LCST) between 61 and 66 °C, as determined by ultraviolet‐visible spectrophotometry and dynamic light scattering. The LCST values increased in proportion to the length of the hydrophilic block and were lower than that of the POEGMA homopolymer. The self‐assembly behavior of the copolymers in aqueous solution was investigated by fluorescence spectroscopy and transmission electron microscopy. The critical micelle concentration value (1.08–0.26 10^?6 mol L^?1) decreased as the length of the POEGMA chain increased. The POEGMA‐PDMS‐POEGMA copolymers can easily self‐assemble into spherical micelles in aqueous solution. Such biocompatible block copolymers may be attractive candidates as ‘‘smart'' thermo‐responsive drug delivery systems. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 2684‐2691     

Poly(ϵ‐caprolactone)‐b‐poly(ethylene glycol)‐b‐poly(ϵ‐caprolactone) triblock copolymers: Synthesis and self‐assembly in aqueous solutions

Nontoxic and biodegradable poly(?‐caprolactone)‐b‐poly(ethylene glycol)‐b‐poly(?‐caprolactone) triblock copolymers were synthesized by the solution polymerization of ?‐caprolactone in the presence of poly(ethylene glycol). The chemical structure of the resulting triblock copolymer was characterized with ¹H NMR and gel permeation chromatography. In aqueous solutions of the triblock copolymers, the micellization and sol–gel‐transition behaviors were investigated. The experimental results showed that the unimer‐to‐micelle transition did occur. In a sol–gel‐transition phase diagram obtained by the vial‐tilting method, the boundary curve shifted to the left, and the gel regions expanded with the increasing molecular weight of the poly(?‐caprolactone) block. In addition, the hydrodynamic diameters of the micelles were almost independent of the investigated temperature (25–55 °C). The atomic force microscopy results showed that spherical micelles formed at the copolymer concentration of 2.5 × 10^?4 g/mL, whereas necklace‐like and worm‐like shapes were adopted when the concentration was 0.25 g/mL, which was high enough to form a gel. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 605–613, 2007     

Synthesis and self‐assembling of poly(N‐isopropylacrylamide‐block‐poly(L‐lactide)‐block‐poly(N‐isopropylacrylamide) triblock copolymers prepared by combination of ring‐opening polymerization and atom transfer radical polymerization

Novel thermo‐responsive poly(N‐isopropylacrylamide)‐block‐poly(l ‐lactide)‐block‐poly(N‐isopropylacylamide) (PNIPAAm‐b‐PLLA‐b‐PNIPAAm) triblock copolymers were successfully prepared by atom transfer radical polymerization of NIPAAm with Br‐PLLA‐Br macroinitiator, using a CuCl/tris(2‐dimethylaminoethyl) amine (Me₆TREN) complex as catalyst at 25 °C in a N,N‐dimethylformamide/water mixture. The molecular weight of the copolymers ranges from 18,000 to 38,000 g mol^?1, and the dispersity from 1.10 to 1.28. Micelles are formed by self‐assembly of copolymers in aqueous medium at room temperature, as evidenced by ¹H NMR, dynamic light scattering (DLS) and transmission electron microscopy (TEM). The critical micelle concentration determined by fluorescence spectroscopy ranges from 0.0077 to 0.016 mg mL^?1. ¹H NMR analysis in selective solvents confirmed the core‐shell structure of micelles. The copolymers exhibit a lower critical solution temperature (LCST) between 32.1 and 32.8 °C. The micelles are spherical in shape with a mean diameter between 31.4 and 83.3 nm, as determined by TEM and DLS. When the temperature is raised above the LCST, micelle size increases at high copolymer concentrations due to aggregation. In contrast, at low copolymer concentrations, decrease of micelle size is observed due to collapse of PNIPAAm chains. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3274–3283     

Thermo‐ and pH‐induced self‐assembly of P(AA‐b‐NIPAAm‐b‐AA) triblock copolymers synthesized via RAFT polymerization

A series of environmentally sensitive ABA triblock copolymers with different block lengths were prepared by reversible addition‐fragmentation chain transfer (RAFT) polymerization from acrylic acid (AA) and N‐isopropylacrylamide (NIPAAm). The GPC and ¹H NMR analyses demonstrated the narrow molecular weight distribution and precise chemical structure of the prepared P(AA‐b‐NIPAAm‐b‐AA) triblock copolymers owing to the controlled/living characteristics of RAFT polymerization. The lower critical solution temperature (LCST) of the triblock copolymers could be tailored by adjusting the length of PAA block and controlled by the pH value. Under heating, the triblock copolymers underwent self‐assemble in dilute aqueous solution and formed nanoparticles revealed via TEM images. Physically crosslinked nanogels induced by inter‐/intra‐hydrogen bonding or core‐shell micelle particles thus could be obtained by changing environmental conditions. With a well‐defined structure and stimuli‐responsive properties, the P(AA‐b‐NIPAAm‐b‐AA) copolymer is expected to be employed as a nanocarrier for biomedical applications in controlled‐drug delivery and targeting therapy. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 1109–1118     

Synthesis and characterization of biodegradable triblock copolymers based on bacterial poly[(R)‐3‐hydroxybutyrate] by atom transfer radical polymerization

Biodegradable poly(tert‐butyl acrylate)–poly[(R)‐3‐hydroxybutyrate]–poly (tert‐butyl acrylate) triblock copolymers based on bacterial poly[(R)‐3‐hydroxybutyrate] (PHB) were synthesized by atom transfer radical polymerization. The chain architectures of the triblock copolymers were confirmed by ¹H NMR and ¹³C NMR spectra. Gel permeation chromatography analysis was used to estimate the molecular weight characteristics and lengths of the PHB and poly(tert‐butyl acrylate) blocks of the copolymers. The thermal properties of the copolymers were studied by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). TGA showed that the triblock copolymers underwent stepwise thermal degradation and had better thermal stability than their respective homopolymers, whereas DSC analyses showed that a microphase‐separation structure was formed only in the triblock copolymers with the longer PHB block. As a similar result, from wide‐angle X‐ray diffraction experimentation, the crystalline phase of PHB could not be seen evidently in the triblock copolymers with the shorter PHB block. The enzymatic hydrolysis of the copolymer films was carried at 37 °C and pH 7.4 in a potassium phosphate buffer with an extracellular PHB depolymerase from Penicillum sp. The biodegradability of the triblock copolymers increased with an increase in the PHB block content. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 4857–4869, 2005     

Synthesis and characterization of poly(L‐lactide‐co‐ε‐caprolactone) (B)‐poly(L‐lactide) (A) ABA block copolymers

ABA triblock copolymers of L ‐lactide (LL) and ε‐caprolactone (CL), designated as PLL‐P(LL‐co‐CL)‐PLL, were synthesized via a two‐step ring‐opening polymerization in bulk using diethylene glycol and stannous octoate as the initiating system. In the first‐step reaction, an approximately 50:50 mol% P(LL‐co‐CL) random copolymer (prepolymer) was prepared as the middle (B) block. This was then chain extended in the second‐step reaction by terminal block polymerization with more L ‐lactide. The percentage yields of the triblock copolymers were in excess of 95%. The prepolymers and triblock copolymers were characterized using a combination of dilute‐solution viscometry, gel permeation chromatography (GPC), ¹H‐ and ¹³C‐NMR, and differential scanning calorimetry (DSC). It was found that the molecular weight of the prepolymer was controlled primarily by the diethylene glycol concentration. All of the triblock copolymers had molecular weights higher than their respective prepolymers. ¹³C‐NMR analysis confirmed that the prepolymers contained at least some random character and that the triblock copolymers consisted of additional terminal PLL end (A) blocks. From their DSC curves, the triblock copolymers were seen to be semi‐crystalline in morphology. Their glass transition, solid‐state crystallization, and melting temperature ranges, together with their heats of melting, all increased as the PLL end (A) block length increased. Copyright © 2005 John Wiley & Sons, Ltd.     

Thermogelling behaviors of poly(caprolactone‐b‐ethylene glycol‐b‐caprolactone) triblock copolymer in the presence of hyaluronic acid

In this article, we studied the effect of hyaluronic acid (HA) on thermogelation of poly(caprolactone‐b‐ethylene glycol‐b‐caprolactone) (PCL‐PEG‐PCL) aqueous solution designed as an injectable system for prevention of postsurgical tissue adhesion. The PCL‐PEG‐PCL triblock copolymers were simply synthesized by ring‐opening polymerization of ε‐caprolactone (CL) in the presence of PEG as a polymeric initiator. The synthesized copolymers were confirmed by proton nuclear magnetic resonance (¹H‐NMR) spectroscopy. Possible interactions between HA and PCL‐PEG‐PCL triblock copolymers in the blend were evaluated by Fourier‐transform infrared spectroscopy (FTIR). The effect of HA on the micellization of PCL‐PEG‐PCL aqueous solution was investigated by dye solubilization method and electrophoretic lighting scattering (ELS) spectrophotometer. Also, the thermogelling behaviors of the PCL‐PEG‐PCL triblock copolymers in the presence of HA and their mechanism were investigated by test tube inverting method, ¹³C‐NMR, ¹H‐NMR, Advanced Rheometic Expansion System (ARES), and differential scanning calorimetry (DSC). The PCL‐PEG‐PCL/HA blend aqueous solutions undergo the sol‐gel‐sol transition in response to an increase in temperature (10–60 °C) and the gelation of the PCL‐PEG‐PCL was rather accelerated by HA. Presumably, this accelerated gelation seems to arise from the attractive interactions between them and the effect of chain confinement in the micelle corona region. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 3629–3637, 2008     

Synthesis,pH‐ and temperature‐induced micellization and gelation of doubly hydrophilic triblock copolymer of poly(N,N‐dimethylamino‐2‐ethylmethacrylate)‐b‐poly(ethylene glycol)‐b‐poly(N,N‐dimethylamino‐2‐ethylmethacrylate) in aqueous solutions

A doubly hydrophilic triblock copolymer of poly(N,N‐dimethylamino‐2‐ethyl methacrylate)‐b‐Poly(ethylene glycol)‐b‐poly(N,N‐dimethylamino‐2‐ethylmethacrylate) (PDMAEMA‐b‐PEG‐b‐PDMAEMA) with well‐defined structure and narrow molecular weight distribution (M_w/M_n = 1.21) was synthesized in aqueous medium via atom transfer radical polymerization (ATRP) of N,N‐dimethylamino‐2‐ethylmethacrylate (DMAEMA) initiated by the PEG macroinitiator. The macroinitiator and triblock copolymer were characterized with ¹H NMR and gel permeation chromatography (GPC). Fluorescence spectroscopy, dynamic light scattering (DSL), transmittance measurement, and rheological characterization were applied to investigate pH‐ and temperature‐induced micellization in the dilute solution of 1 mg/mL when pH > 13 and gelation in the concentrated solution of 25 wt % at pH = 14 and temperatures beyond 80 °C. The unimer of R_h = 3.7 ± 0.8 nm coexisted with micelle of R_h = 45.6 ± 6.5 nm at pH 14. Phase separation occurred in dilute aqueous solution of the triblock copolymer of 1 mg/mL at about 50 °C. Large aggregates with R_h = 300–450 nm were formed after phase separation, which became even larger as R_h = 750–1000 nm with increasing temperature. The gelation temperature determined by rheology measurement was about 80 °C at pH 14 for the 25 wt % aqueous solution of the triblock copolymer. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 5869–5878, 2008     

Thermo‐sensitive amphiphilic poly(N‐vinylcaprolactam) copolymers: synthesis and solution properties

Thermo‐sensitive amphiphilic copolymers, PVCL‐PTrpAMT and PVCL‐PVP‐PTrpAMT of hydrophilic N‐vinylcaprolactam (VCL), N‐vinylpyrrolidone (NVP), and hydrophobic N‐t‐Boc‐tryptophanamido‐N′‐methacryl thioureas (TrpAMT) monomers, were synthesized and characterized by ¹H NMR, UV‐spectroscopy, and GPC‐MALLS. The cloud point (CP) measurement showed that hydrophobic PTrpAMT and hydrophilic PVP segments significantly altered the phase transition temperature of PVCL with comparable molecular weight in aqueous solution. The CP of PVP‐PTrpAMT solution was 38.0°C, lower by 5.0°C than that of unmodified PVCL. In the presence of phosphate buffer saline (PBS), the CP value of the PVCL polymer decreased by ～2.0°C in comparison to that of the aqueous solution. Fluorescent spectroscopy and TEM studies revealed that PVCL‐PTrpAMT and PVCL‐PVP‐PTrpAMT self‐assembled into the spherical micelles, 30–70 nm in diameter, at concentrations over their CMCs in an aqueous solution. Cytotoxicity tests demonstrated that the PVCL copolymers were not harmful to cell viability, which may favor the use of the copolymers as potential thermo‐sensitive polymers in pharmaceutical applications. Copyright © 2009 John Wiley & Sons, Ltd.     

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     

Stimuli‐responsive ABC triblock copolymers by sequential living cationic copolymerization: Multistage self‐assemblies through micellization to open association

Stimuli‐responsive ABC triblock copolymers with three segments with different phase‐separation temperatures were synthesized via sequential living cationic copolymerization. The triblock copolymers exhibited sensitive thermally induced physical gelation (open association) through the formation of micelles. For example, an aqueous solution of EOVE₂₀₀‐b‐MOVE₂₀₀‐b‐EOEOVE₂₀₀ [where EOVE is 2‐ethoxyethyl vinyl ether, MOVE is 2‐methoxethyl vinyl ether and EOEOVE is 2‐(2‐ethoxy)ethoxyethyl vinyl ether; the order of the phase‐separation temperatures was poly(EOVE) (20 °C) < poly(EOEOVE) (41 °C) < poly(MOVE) (70 °C)] underwent multiple reversible transitions from sol (<20 °C) to micellization (20–41 °C) to physical gelation (physical crosslinking, 41–64 °C) and, finally, to precipitation (>64 °C). At 41–64 °C, the physical gel became stiffer than similar diblock or ABA triblock copolymers of the same molecular weight. Furthermore, the ABC triblock copolymers exhibited Weissenberg effects in semidilute aqueous solutions. In sharp contrast, another ABC triblock copolymer with a different arrangement, EOVE₂₀₀‐b‐EOEOVE₂₀₀‐b‐MOVE₂₀₀, scarcely exhibited any increase in viscosity above 41 °C. The temperatures of micelle formation and physical gelation corresponded to the phase‐separation temperatures of the segment types in the ABC triblock copolymer. No second‐stage association was observed for AB and ABA block copolymers with the same thermosensitive segments found in their ABC counterparts. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 2601–2611, 2004     

Amphiphilic gradient copolymers containing fluorinated 2‐phenyl‐2‐oxazolines: Microwave‐assisted one‐pot synthesis and self‐assembly in water

Here, we present the one‐step synthesis of 2‐(m‐difluorophenyl)‐2‐oxazoline and its use as a monomer for microwave‐assisted statistical cationic ring‐opening copolymerizations (CROP). Well‐defined amphiphilic gradient copolymers, as evidenced by the polymerization kinetics, were prepared using 2‐ethyl‐2‐oxazoline as comonomer and methyl tosylate as initiator in nitromethane at 140 °C. The resulting gradient copolymers (DP = 60 and 100) were characterized by means of size exclusion chromatography and ¹H NMR spectroscopy. In the second part, we focus on a detailed study of the self‐assembly of the copolymers in aqueous solution using atomic force microscopy and dynamic light scattering. Both methods revealed the self‐assembly of the gradient copolymers into spherical micelles. To quantify the influence of the fluorine atoms and the monomer distribution on the self‐assembly, a comparative study with gradient copolymers of 2‐phenyl‐2‐oxazoline and 2‐ethyl‐2‐oxazoline was performed. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 5859–5868, 2008     

Dendron‐like poly(ε‐benzyloxycarbonyl‐L‐lysine)/linear PEO block copolymers: Synthesis,physical characterization,self‐assembly,and drug‐release behavior

Dendron‐like poly(ε‐benzyloxycarbonyl‐L ‐lysine)/linear poly(ethylene oxide) block copolymers (i.e., Dm‐PZLys‐b‐PEO, m = 0 and 3; Dm are the propargyl focal point poly(amido amine) dendrons having 2^m primary amine groups) were for the first time synthesized by combining ring‐opening polymerization (ROP) of ε‐benzyloxycarbonyl‐L ‐lysine N‐carboxyanhydride (Z‐Lys‐NCA) and click chemistry, where Dm‐PZLys homopolypeptides were click conjugated with azide‐terminated PEO. Their molecular structures and physical properties were characterized in detail by FTIR, ¹H NMR, gel permeation chromatography, differential scanning calorimetry, polarized optical microscopy, and wide angle X‐ray diffraction. Both homopolypeptides and copolymers presented a liquid crystalline phase transition for PZLys block, and the transition was irreversible. Moreover, the degree of crystallinity of PEO block within linear copolymers decreased from 96.2% to 20.4% with increasing PZLys composition, whereas that within dendritic copolymers decreased to zero. The secondary conformation of PZLys progressively changed from β‐sheet to α‐helix with increasing the chain length. These copolymers self‐assembled into spherical nanoparticles in aqueous solution, and the anticancer drug doxorubicin‐loaded nanoparticles gave a similar morphology compared with their blank counterparts. The drug‐loaded nanoparticles showed a triphasic drug‐release profile at aqueous pH 7.4 or 5.5 and 37 °C and sustained a longer drug‐release period for about 2 months. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Poly(N‐vinyl pyrrolidone)‐block‐Poly(N‐vinyl carbazole)‐block‐poly(N‐vinyl pyrrolidone) triblock copolymers: Synthesis via RAFT/MADIX process,self‐assembly behavior,and photophysical properties

Poly(N‐vinyl pyrrolidone)‐block‐poly(N‐vinyl carbazole)‐block‐poly(N‐vinyl pyrrolidone) (PVP‐b‐PVK‐b‐PVP) triblock copolymers were synthesized via sequential reversible addition‐fragmentation chain transfer/macromolecular design via the interchange of xanthate (RAFT/MADIX) process. First, 1,4‐phenylenebis(methylene)bis(ethyl xanthate) was used as a chain transfer agent to mediate the radical polymerization of N‐vinyl carbazole (NVK). It was found that the polymerization was in a controlled and living manner. Second, one of α,ω‐dixanthate‐terminated PVKs was used as the macromolecular chain transfer agent to mediate the radical polymerization of N‐vinyl pyrrolidone (NVP) to obtain the triblock copolymers with various lengths of PVP blocks. Transmission electron microscopy (TEM) showed that the triblock copolymers in bulks were microphase‐separated and that PVK blocks were self‐organized into cylindrical microdomains, depending on the lengths of PVP blocks. In aqueous solutions, all these triblock copolymers can self‐assemble into the spherical micelles. The critical micelle concentrations of the triblock copolymers were determined without external adding fluorescence probe. By analyzing the change in fluorescence intensity as functions of the concentration, it was judged that the onset of micellization occurred at the concentration while the FL intensity began negatively to deviate from the initial linear increase with the concentration. Fluorescence spectroscopy indicates that the self‐assembled nanoobjects of the PVP‐b‐PVK‐b‐PVP triblock copolymers in water were capable of emitting blue/or purple fluorescence under the irradiation of ultraviolet light. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 1852–1863     

Stimuli‐responsive 4‐acryloylmorpholine/4‐acryloylpiperidine copolymers via nitroxide mediated polymerization

4‐acryloylmorpholine/4‐acryloylpiperidine statistical copolymers were synthesized by nitroxide mediated polymerization (NMP) with BlocBuilder unimolecular initiator in dimethylformamide solution at 120 °C. The copolymers had narrow molecular weight distributions (dispersity ? = 1.25–1.35, number average molecular weights M _n = 8.5–13.7 kg mol^?1). The copolymer microstructure was essentially statistical (reactivity ratios r _4AP = 0.81 ± 0.73, r _4AM = 0.73 ± 0.68 based on non‐linear fitting of the Mayo‐Lewis equation). Cloud point temperatures (CPT) in aqueous media were tuned from 11 °C to 92 °C, merely by adjusting the initial monomer composition. Using NMP permitted sharper control of the CPT transitions, compared to the similar copolymer made using conventional radical polymerization. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55 , 2160–2170     

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     

Fabrication of thermosensitive PCL‐PNIPAAm‐PCL triblock copolymeric micelles for drug delivery

A series of thermosensitive ABA type triblock poly(ε‐caprolactone)‐b‐poly(N‐isopropylacrylamide)‐b‐poly(ε‐caprolactone) (PCL‐PNIPAAm‐PCL) copolymers with different molecular weights were synthesized by the combination of ring opening polymerization and reversible addition‐fragmentation chain transfer (RAFT) polymerization. The critical micelle concentrations (CMCs) of the resulted four triblock copolymers in aqueous solution were determined to be 33.8, 39.8, 35.5, and 41.7 mg/L, respectively, by fluorescence spectroscopy using pyrene as a fluorescence probe. Optical absorption measurements showed that the lower critical solution temperatures (LCSTs) of the copolymers were 35.8, 36.2, 35.2, and 36.2 °C, respectively, in distilled water, and 33.9, 34.2, 33.3, 34.6 °C, respectively, in PBS (pH = 6.8, I = 0.1). Transmission electron microscopy (TEM) showed that the self‐assembled micelles exhibited a well‐defined spherical shape with diameter of around 100 nm. The drug‐loaded PCL‐PNIPAAm‐PCL micelles displayed thermosensitive controlled release behaviors. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 3048–3057, 2008     

Temperature‐induced aggregation of the copolymers of N‐isopropylacrylamide and sodium 2‐acrylamido‐2‐methyl‐1‐propanesulphonate in aqueous solutions

A series of random copolymers of N‐isopropylacrylamide (NIPAM) and sodium 2‐acrylamido‐2‐methyl‐1‐propanesulphonate (AMPS) was synthesized by free‐radical copolymerization. The content of AMPS in the copolymers ranged from 1.1 to 9.6 mol %. The lower critical‐solution temperature (LCST) of copolymers in water increased strongly with an increasing content of AMPS. The influence of polymer concentration on the LCST of the copolymers was studied. For the copolymers with a higher AMPS content, the LCST decreased faster with an increasing concentration than for copolymers with a low content of AMPS. For a copolymer containing 1.1 mol % of AMPS the LCST dropped by about 3 °C when the concentration increased from 1 to 10 g/L, whereas for a copolymer containing 9.6 mol % of AMPS the LCST dropped by about 10 °C in the concentration range from 2 to 10 g/L. It was observed that the ionic strength of the aqueous polymer solution very strongly influences the LCST. This effect was most visible for the copolymer with the highest content of AMPS (9.6 mol %) for which an increase in the ionic strength from 0.2 to 2.0 resulted in a decrease in the LCST by about 27 °C (from 55 to 28 °C), whereas for the copolymer containing 1.1 mol % of AMPS the LCST decreased only by about 6 °C (from 37 to 31 °C) when the ionic strength increased from 0.005 to 0.3. The reactivity ratios for the AMPS and NIPAM monomer pairs were determined using different methods. The values of r_AMPS and r_NIPAM obtained were 11.0–11.6 and 2.1–2.4, respectively. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 2784–2792, 2001