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.     

Non‐catalyst synthesis and in vitro drug release property of poly(5,5‐dimethyl‐1,3‐dioxan‐2‐one)‐block‐methoxy poly(ethylene glycol) copolymers

A series of poly(5,5‐dimethyl‐1,3‐dioxan‐2‐one)‐block‐methoxy poly(ethylene glycol) (PDTC‐b‐mPEG) copolymers were synthesized by the ring‐opening polymerization of 5,5‐dimethyl‐1,3‐dioxan‐2‐one (DTC) in bulk, using methoxy poly(ethylene glycol) (mPEG) as initiator without adding any catalysts. The resulting copolymers were characterized by Fourier transform infrared spectra, ¹H NMR and gel permeation chromatography. The influences of some factors such as the DTC/mPEG molar feed ratio, reaction time and reaction temperature on the copolymerization were investigated. The experimental results showed that mPEG could effectively initiate the ring‐opening polymerization of DTC in the absence of catalyst, and that the copolymerization conditions had a significant effect on the molecular weight of PDTC‐b‐mPEG copolymer. In vitro drug release study demonstrated that the amount of indomethacin released from PDTC‐b‐mPEG copolymer decreased with increase in the DTC content in the copolymer. © 2013 Society of Chemical Industry     

Excellent biocompatible polymeric membranes prepared via layer‐by‐layer self‐assembly

Excellent biocompatible polymeric membranes were prepared by combining the antifouling property of poly(ethylene glycol) methyl ether (mPEG) and the anticoagulant property of poly(sodium p‐styrene sulfonate) (PSS). Block copolymers of poly(ethylene glycol) methyl ether‐b‐poly(sodium p‐styrene sulfonate) (mPEG‐b‐PSS) with different chain lengths were synthesized by ATRP using mPEG macroinitiator. The copolymers were then used to modify polyethersulfone (PES) membrane via layer‐by‐layer (LBL) self‐assembly technology. The chemical compositions, surface morphologies and hydrophilicity of the modified membranes were characterized, indicating that the mPEG‐b‐PSS copolymers were successfully deposited on the membranes surfaces. Then, the blood compatibility and cytocompatibility of the modified membranes were systematically investigated. The results indicated that the mPEG‐b‐PSS copolymers could improve the hydrophilicity and the resistance to protein adsorption, and had great effect on suppressing platelet adhesion, prolonging clotting times, and improving cytocompatibility. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41245.     

Lipase‐catalyzed synthesis of polymeric prodrugs of nonsteroidal anti‐inflammatory drugs

Because of the potential application of prodrugs of nonsteroidal anti‐inflammatory drugs (NSAIDs), Candida antarctica lipase B (CAL‐B) catalyzed polycondensation of profen‐containing diol monomers and diesters were designed to prepare a series of biodegradable polymeric prodrugs composed of NSAID branches and poly(amide‐co‐ester) backbone. The structure of the products was confirmed by Fourier transform infrared spectroscopy, NMR, and gel permeation chromatography (GPC). The reaction conditions of polymerization, such as the enzyme source, amount of catalyst, and temperature, were optimized. The molecular weights of resultant copolymers were 2170–13,270 g/mol, with corresponding polydispersities from 1.17 to 2.4. The copolymers had relatively high drug loadings of 44.7–59.7 wt % because every repeat unit contained one drug molecule. The strategy of enzymatic polymerization appeared to be quite general and accommodated a large number of comonomer substrates with various chain lengths and substituents. The optically pure (R)‐naproxen monomer was demonstratively incorporated into the corresponding copolymers with the developed synthesis strategy. The in vitro study showed that the polyester could release the drug effectively under physiological conditions with enzyme, which indicated that the obtained product could be a promising prodrug for extending pharmacological effects by delayed drug release. With GPC analysis, we confirmed that the prodrug was completely degradable in aqueous solution. The attractive features of the copolymer were its high drug loading, biodegradability, and biocompatibility. The high tolerance of the CAL‐B toward drug groups, as described in this article, provides a new route for synthesizing polymeric drugs with potential biomedical applications in mild conditions and for reducing environmental impact. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Gadolinium‐conjugated FA‐PEG‐PAMAM‐COOH nanoparticles as potential tumor‐targeted circulation‐prolonged macromolecular MRI contrast agents

The aim of research is to develop potential tumor‐targeted circulation‐prolonged macromolecular magnetic resonance imaging (MRI) contrast agents without the use of low molecular gadolinium (Gd) ligands. The contrast agents were based on polymer–metal complex nanoparticles with controllable particle size to achieve the active and passive tumor‐targeted potential. In particular, poly (amidoamine) (PAMAM) dendrimer with 32 carboxylic groups was modified with folate‐conjugated poly (ethyleneglycol) amine (FA‐PEG‐NH₂, M_w: 2 k and 4 kDa). FA‐PEG‐PAMAM‐Gd macromolecular MRI contrast agents were prepared by the complex reaction between the carboxylic groups in PAMAM and GdCl₃. The structure of FA‐PEG‐PAMAM‐COOH was confirmed by nuclear magnetic resonance (¹H‐NMR), Fourier transform infrared (FTIR) spectra, and electrospray ionization mass spectra (ESI‐MS). The mass percentage content of Gd (III) in FA‐PEG‐PAMAM‐Gd was measured by inductively coupled plasma‐atomic emission spectrometer (ICP‐AES). The sizes of these nanoparticles were about 70 nm measured by transmission electron microscopy, suggestion of their passive targeting potential to tumor tissue. In comparison with clinically available small molecular Gadopentetate dimeglumine, FA‐PEG‐PAMAM‐Gd showed comparable cytotoxicity and higher relaxation rate, suggestion of their great potential as tumor‐targeted nanosized macromolecular MRI contrast agents due to the overexpressed FA receptor in human tumor cell surfaces. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Polycarbonate microspheres containing tumor necrosis factor‐α genes and magnetic powder as potential cancer therapeutics

Amphiphilic polycarbonate copolymers including methoxy‐terminated poly(ethylene glycol)‐co‐poly (5,5‐dimethyl trimethylene carbonate) [Poly(PEG‐b‐TMC)] and poly(ethylene glycol)‐co‐poly(trimethylene carbonate) [Poly(PEG‐b‐DTC)] were synthesized. The water‐in‐oil‐in‐water (W/O/W) solvent evaporation technique was adopted to produce anticancer magnetic Poly(PEG‐b‐DTC) microspheres containing tumor necrosis factor‐α (TNF‐α) genes and Fe₃O₄ magnetic ultrafine powder. Drug release studies showed that the microspheres can sustain a steady release rate of TNF‐α genes in 0.1M phosphate buffer saline solution in vitro for up to 60 h. In vitro cytotoxicity assays demonstrated that the microspheres have high inhibition and antitumor action to human hepatocellular carcinoma (Bel‐7204) cells in vitro. In vivo inhibition on the growth of hepatic carcinomas and histopathologic observation indicated that the microspheres possess a markedly high antitumor activity to human hepatocellular carcinoma (Bel‐7204). © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Encapsulation of diclofenac sodium with acidic copolymer hydrogels based on PEG/poly(N‐isopropylacrylamide‐co‐2‐acrylamido‐2‐methyl‐1‐propanesulfonic acid) semi‐interpenetrating network using in situ loading technique

A pH‐ and temperature‐responsive semi‐interpenetrating copolymer PEG6000/poly(NIPA‐co‐AMPS) (PEG/AMPS‐co‐NIPA SIPN), for short PEG SIPN, was made by ammonium persulfate‐initiated suspension copolymerization of N‐isopropylacrylamide, 2‐acrylamido‐2‐methylpropanesulphonic acid, and N,N′‐methylene‐bis‐acrylamide (MBAA; crosslinker) in the presence of PEG6000. The PEG SIPN copolymer matrices containing nanostructures made in the high‐temperature copolymerization resulted in channels for PEG and facile migration of drugs. In drug encapsulation or drug‐loading process, one can easily ignore or pay less attention to the interaction between a drug and its encapsulation materials; however, the ignored interactions may induce problems in drug properties or the release behavior in use. Sodium diclofenac (DFNa) precipitates as the carboxylic acid form in an acidic environment, and it is challenging to encapsulate sodium diclofenac in such an acidic matrix without precipitation of the sparingly soluble acid form of DFNa on the surface of the polymer substrate. To avoid bulky precipitation in drug loading, an in situ loading technique was developed for producing gel spheres with DFNa uniformly distributed in the polymer matrix. The technique is based on fast polymerization of spherical droplets of a pregel solution in which the drug is dissolved. Diffusion‐loading prodrugs were made in comparison with in situ loading prodrugs in thermal, release kinetics, and release behavior. Drug release profiles (in pH 7.4 phosphate buffer) show that the new drug loading technique gives controlled release during a period of about 7 days at 37°C. By contrast, gel spheres loaded with sodium diclofenac using the conventional diffusion technique produced almost total release of the drug within about 24 h. The thermal stability of sodium diclofenac, the PEG/AMPS‐co‐NIPA SIPN, and the prodrugs made with the SIPN and sodium diclofenac was studied. A near zero‐order release kinetics was found in the in vitro release of sodium diclofenac with in situ loading PEG SIPN prodrug. We have, for the first time, studied sodium diclofenac release behavior from the PEG SIPN hydrogel systems. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Short poly(ethylene glycol) block initiation of poly(l‐lactide) di‐block copolymers: a strategy for tuning the degradation of resorbable devices

The current range of medical applications of resorbable polyesters could be hugely expanded if more effective strategies for tailoring degradation rate were available. Block copolymerisation with poly(ethylene glycol) (PEG) has been shown to reduce degradation times; however, to date, this has relied on the addition of PEG to short lengths of polyester. This results in copolymers with high fractions of PEG and low molecular weights, reducing the potential range of applications. Furthermore, there has been no systematic study of the relative lengths of the blocks. In this work, we employed short hydroxyl‐functionalised methoxy‐terminated mPEG to initiate the synthesis of poly(l ‐lactide) (PLLA), resulting in controlled di‐block copolymers with short mPEG blocks and long PLLA blocks. A controlled series of polymers was made with PLLA lengths (60 < M_n (kg mol^?1) < 200) and mPEG lengths (550 < M_n (g mol^?1) < 5000) giving very low mPEG content (0.1–1.5 wt%). We found that, despite the low fraction of mPEG, water uptake and the rate of hydrolytic degradation, k, increased. Significantly, k for the polymers was dependent only on the presence of mPEG, and was little affected by mPEG length or PLLA length in the ranges studied. Moreover, mass loss began in all polymers when M_n of the polymer fell below a threshold of about 20 kg mol^?1 and depended on both the initial molecular weight of PLLA and the presence (but not the length) of mPEG. Short‐chain mPEG therefore provides a new route for targeted, temporal control of resorbable polyesters for biomedical devices. © 2018 The Authors. Polymer International published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.     

Synthesis and characterization of poly(ε‐caprolactone)‐b‐poly(ethylene glycol)‐b‐poly(ε‐caprolactone) triblock copolymers with dibutylmagnesium as catalyst

Two series of poly(ε‐caprolactone)‐b‐poly(ethylene glycol)‐b‐poly(ε‐caprolactone) triblock copolymers were prepared by the ring opening polymerization of ε‐caprolactone in the presence of poly(ethylene glycol) and dibutylmagnesium in 1,4‐dioxane solution at 70°C. The triblock structure and molecular weight of the copolymers were analyzed and confirmed by ¹H NMR, ¹³C NMR, FTIR, and gel permeation chromatography. The crystallization and thermal properties of the copolymers were investigated by wide‐angle X‐ray diffraction (WAXD) and differential scanning calorimetry (DSC). The results illustrated that the crystallization and melting behaviors of the copolymers were depended on the copolymer composition and the relative length of each block in copolymers. Crystallization exothermal peaks (T_c) and melting endothermic peaks (T_m) of PEG block were significantly influenced by the relative length of PCL blocks, due to the hindrance of the lateral PCL blocks. With increasing of the length of PCL blocks, the diffraction and the melting peak of PEG block disappeared gradually in the WAXD patterns and DSC curves, respectively. In contrast, the crystallization of PCL blocks was not suppressed by the middle PEG block. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Preparation and properties of water‐soluble polyester surfactants. I. Preparation and surface activity of poly(ethylene glycol)‐dimethyl 5‐sulfo‐isophthalate sodium salt polyester surfactants

The reaction of poly(ethylene glycol) (PEG, number‐average molecular weight M_n = 400‐2000) and dimethyl 5‐sulfoisophthalate sodium salt (SIPM) synthesized a series of anionic polymeric surfactants having a range of molecular weights. ¹H‐NMR, FTIR, and elemental analysis were employed to characterize the structures of these compounds. Also, the influences of the PEG segment lengths of PEG/SIPM copolymers on the surface tension, foaming properties, wetting power, and dispersant properties were investigated. The experimental results indicated that the solution that contained the PEG/SIPM copolymer surfactants exhibited excellent surface‐active properties. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 2727–2731, 2002     

Comparison of micelles formed by amphiphilic poly(ethylene glycol)‐b‐poly(trimethylene carbonate) star block copolymers

In this article, we describe the synthesis and solution properties of PEG‐b‐PTMC star block copolymers via ring‐opening polymerization (ROP) of trimethylene carbonate (TMC) monomer initiated at the hydroxyl end group of the core PEG using HCl Et₂O as a monomer activator. The ROP of TMC was performed to synthesize PEG‐b‐PTMC star block copolymers with one, two, four, and eight arms. The PEG‐b‐PTMC star block copolymers with same ratio of between hydrophobic PTMC and hydrophilic PEG segments were obtained in quantitative yield and exhibited monomodal GPC curves. The amphiphilic PEG‐b‐PTMC star block copolymers formed spherical micelles with a core–shell structure in an aqueous phase. The mean hydrodynamic diameters of the micelles increased from 17 to 194 nm with increasing arm number. As arm number increased, the critical micelle concentration (CMC) of the PEG‐b‐PTMC star block copolymers increased from 3.1 × 10^?3 to 21.1 × 10^?3 mg/mL but the partition equilibrium constant, which is an indicator of the hydrophobicity of the micelles of the PEG‐b‐PTMC star block copolymers in aqueous media, decreased from 4.44 × 10⁴ to 1.34 × 10⁴. In conclusion, we confirmed that the PEG‐b‐PTMC star block copolymers form micelles and, hence, may be potential hydrophobic drug delivery vehicles. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

The role of the ratio (PEG:PPG) of a triblock copolymer (PPG‐b‐PEG‐b‐PPG) in the cure kinetics,miscibility and thermal and mechanical properties in an epoxy matrix

The aim of this study was to evaluate the role of different poly(ethylene glycol):poly(propylene glycol) (PEG:PPG) molar ratios in a triblock copolymer in the cure kinetics, miscibility and thermal and mechanical properties in an epoxy matrix. The poly(propylene glycol)‐block‐poly(ethylene glycol)‐block‐poly(propylene glycol) (PPG‐b‐PEG‐b‐PPG) triblock copolymers used had two different molecular masses: 3300 and 2000 g mol^?1. The mass concentration of PEG in the copolymer structure played a key role in the miscibility and cure kinetics of the blend as well as in the thermal–mechanical properties. Phase separation was observed only for blends formed with the 3300 g mol^?1 triblock copolymer at 20 wt%. Concerning thermal properties, the miscibility of the copolymer in the epoxy matrix reduced the T_g value by 13 °C, although a 62% increase in fracture toughness (K_IC) was observed. After the addition of PPG‐b‐PEG‐b‐PPG with 3300 g mol^?1 there was a reduction in the modulus of elasticity by 8% compared to the neat matrix; no significant changes were observed in T_g values for the immiscible system. The use of PPG‐b‐PEG‐b‐PPG with 2000 g mol^?1 reduced the modulus of elasticity by approximately 47% and increased toughness (K_IC) up to 43%. Finally, for the curing kinetics of all materials, the incorporation of the triblock copolymer PPG‐b‐PEG‐b‐PPG delayed the cure reaction of the DGEBA/DDM (DGEBA, diglycidyl ether of bisphenol A; DDM, Q3‐4,4′‐Diaminodiphenylmethane) system when there is miscibility and accelerated the cure reaction when it is immiscible. All experimental curing reactions could be fitted to the Kamal autocatalytic model presenting an excellent agreement with experimental data. This model was able to capture some interesting features of the addition of triblock copolymers in an epoxy resin. © 2018 Society of Chemical Industry     

Antitumor efficacy of doxorubicin encapsulated within PEGylated poly(amidoamine) dendrimers

We report here a general approach to using poly(amidoamine) (PAMAM) dendrimers modified with polyethylene glycol (PEG) as a platform to encapsulate an anticancer drug doxorubicin (DOX) for in vitro cancer therapy applications. In this approach, PEGylated PAMAM dendrimers were synthesized by conjugating monomethoxypolyethylene glycol with carboxylic acid end group (mPEG‐COOH) onto the surface of generation 5 amine‐terminated PAMAM dendrimer (G5.NH₂), followed by acetylation of the remaining dendrimer terminal amines. By varying the molar ratios of mPEG‐COOH/G5.NH₂, G5.NHAc‐mPEG_n (n = 5, 10, 20, and 40, respectively) with different PEGylation degrees were obtained. We show that the PEGylated dendrimers are able to encapsulate DOX with approximately similar loading capacity regardless of the PEGylation degree. The formed dendrimer/DOX complexes are water soluble and stable. In vitro release studies show that DOX complexed with the PEGylated dendrimers can be released in a sustained manner. Further cell viability assay in conjunction with cell morphology observation demonstrates that the G5.NHAc‐mPEG_n/DOX complexes display effective antitumor activity, and the DOX molecules encapsulated within complexes can be internalized into the cell nucleus, similar to the free DOX drug. Findings from this study suggest that PEGylated dendrimers may be used as a general drug carrier to encapsulate various hydrophobic drugs for different therapeutic applications. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40358.     

Synthesis,characterization, and in vitro drug‐release properties of 2‐hydroxyethyl methacrylate copolymers

2‐Hydroxyethyl methacrylate was copolymerized with acrylamide, N‐vinyl‐2‐pyrrolidone, and n‐butyl methacrylate by free‐radical solution polymerization with α,α′‐azobisisobutyronitrile as an initiator at 70 ± 1°C. The average molecular weights and molar compositions of the resultant copolymers were determined with gel permeation chromatography and ¹H‐NMR spectroscopy data, respectively. Diclofenac or 2‐[(2,6‐dichlorophenyl)amino]benzene acetic acid, a nonsteroidal anti‐inflammatory drug, was chemically attached to the copolymers by transesterification reaction in the presence of N,N′‐dicyclohexylcarbodiimide to give macromolecular prodrugs. All the synthesized polymers were characterized with Fourier transform infrared, ¹H‐, and ¹³C‐NMR spectroscopy techniques. The polymer–drug conjugates were hydrolyzed in cellophane member dialysis bags containing aqueous buffered solutions (pH 8) at 37°C, and the hydrolysis solutions were detected by UV spectrophotometer at selected intervals. The results showed that the drug could be released by selective hydrolysis of the ester bond from the side chain of the drug moiety. The release profiles of the drug indicated that the hydrolytic behavior of polymeric prodrugs strongly depends on the hydrophilicity of the polymer. The results suggest that the synthesized copolymers could be useful carriers for the release of diclofenac in controlled‐release systems. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 2403–2409, 2007     

Influence of the synthesis conditions on the structural and thermal properties of poly(l‐lactide)‐b‐poly(ethylene glycol)‐b‐poly(l‐lactide)

The poly(l ‐lactide)‐b‐poly(ethylene glycol)‐b‐poly(l ‐lactide) block copolymers (PLLA‐b‐PEG‐b‐PLLA) were synthesized in a toluene solution by the ring‐opening polymerization of 3,6‐dimethyl‐1,4‐dioxan‐2,5‐dione (LLA) with PEG as a macroinitiator or by transterification from the homopolymers [polylactide and PEG]. Two polymerization conditions were adopted: method A, which used an equimolar catalyst/initiator molar ratio (1–5 wt %), and method B, which used a catalyst content commonly reported in the literature (<0.05 wt %). Method A was more efficient in producing copolymers with a higher yield and monomer conversion, whereas method B resulted in a mixture of the copolymer and homopolymers. The copolymers achieved high molar masses and even presenting similar global compositions, the molar mass distribution and thermal properties depends on the polymerization method. For instance, the suppression of the PEG block crystallization was more noticeable for copolymer A. An experimental design was used to qualify the influence of the catalyst and homopolymer amounts on the transreactions. The catalyst concentration was shown to be the most important factor. Therefore, the effectiveness of method A to produce copolymers was partly due to the transreactions. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40419.     

pH‐responsive poly(ethylene glycol)‐poly(ϵ‐caprolactone)‐poly(glutamic acid) polymersome as an efficient doxorubicin carrier for cancer therapy

The synthesis, characterization and potential application in the doxorubicin (Dox) delivery system of a biodegradable polypeptide‐based block copolymer, poly(ethylene glycol)₂₀₀₀‐poly(?‐caprolactone)₆₀₀₀‐poly(glutamic acid)₁₀₀₀ (PEG₂₀₀₀‐PCL₆₀₀₀‐PGA₁₀₀₀), was investigated. The copolymer was synthesized via ring‐opening polymerization and characterized by ¹H NMR and Fourier transform IR. The synthesized copolymer could self‐assemble into aggregates and the critical aggregation concentration was 0.23 mg mL^?1. Transmission electron microscopy indicated that spherical polymersomes formed with a desirable size about 180 nm. Therefore Dox was encapsulated into these polymersomes, and then we investigated its applications in a drug delivery system. These Dox‐loaded polymersomes (PolyDox) were characterized by dynamic light scattering, zeta potential and pH responsiveness measurements. In vitro drug release indicated that the release rate of drug from PolyDox was pH‐responsive and significantly decreased. The drug pharmacokinetic parameters were improved in comparison to the group treated with free Dox, which proved the prolonged Dox release from PolyDox. A WST‐1 assay indicated a low toxicity and good compatibility of copolymer to cells within 48 h. The results also showed that PolyDox appeared to induce a higher anti‐tumor effect. Cell uptake results indicated that PolyDox displayed higher cellular uptake in A549 cells. Endocytosis inhibition results demonstrated that the internalization of PolyDox was mostly mediated by the fluid‐phase endocytosis pathway. © 2017 Society of Chemical Industry     

Synthesis of double‐hydrophilic poly(methylacrylic acid)–poly(ethylene glycol)–poly(methylacrylic acid) triblock copolymers and their micelle formation

The aim of the work reported was to synthesize a series of double‐hydrophilic poly(methacrylic acid)‐block‐poly(ethylene glycol)‐block‐poly(methacrylic acid) (PMAA‐b‐PEG‐b‐PMAA) triblock copolymers and to study their self‐assembly behavior. These copolymeric self‐assembly systems are expected to be potential candidates for applications as carriers of hydrophilic drugs. Bromo‐terminated difunctional PEG macroinitiators were used to synthesize well‐defined triblock copolymers of poly(tert‐butyl methacrylate)‐block‐poly(ethylene glycol)‐block‐poly(tert‐butyl methacrylate) via reversible‐deactivation radical polymerization. After the removal of the tert‐butyl group by hydrolysis, double‐hydrophilic PMAA‐b‐PEG‐b‐PMAA triblock copolymers were obtained. pH‐sensitive spherical micelles with a core–corona structure were fabricated by self‐assembly of the double‐hydrophilic PMAA‐b‐PEG‐b‐PMAA triblock copolymers at lower solution pH. Transmission electron microscopy and laser light scattering studies showed the micelles were of nanometric scale with narrow size distribution. Solution pH and micelle concentration strongly influenced the hydrodynamic radius of the spherical micelles (48–310 nm). A possible reason for the formation of the micelles is proposed. Copyright © 2010 Society of Chemical Industry     

Synthesis and characterization of multi‐block copolymers containing poly [(3‐hydroxybutyrate)‐co‐(3‐hydroxyvalerate)] and poly(ethylene glycol)

Various problems, including high crystallinity, high melting temperature, poor thermal stability, hydrophobicity and brittleness, have impeded many practical applications of poly[(3‐hydroxybutyrate)‐co‐(3‐hydroxyvalerate)] (PHBV) as an environmentally friendly material and biomedical material. In the work reported here, multi‐block copolymers containing PHBV and poly(ethylene glycol) (PHBV‐b‐PEG) were synthesized with telechelic hydroxylated PHBV as a hard and hydrophobic segment, PEG as a soft and hydrophilic segment and 1,6‐hexamethylene diisocyanate as a coupling reagent to solve the problems mentioned above. PHBV and PEG blocks in PHBV‐b‐PEG formed separate crystalline phases with lower crystallinity levels and lower melting temperatures than those of phases formed in the precursors. The crystallite dimensions of the two blocks in PHBV‐b‐PEG were smaller than those of the corresponding precursors. Compared to values for the original PHBV, the maximum decomposition temperature of the PHBV block in PHBV‐b‐PEG was 16.0 °C higher and the water contact angle was 9° lower. In addition, the elongation at break was 2.8% for a pure PHBV fiber but 20.9% for a PHBV/PHBV‐b‐PEG fiber with a PHBV‐b‐PEG content of 30%. PHBV‐b‐PEGs can overcome some of the disadvantages of pure PHBV; it is possible that PHBV might be a good candidate for the formulation of environmentally friendly materials and biomedical materials. Copyright © 2010 Society of Chemical Industry     

Synthesis and self‐assembly of amphiphilic star‐block copolymers consisting of polyethylene and poly(ethylene glycol) segments

We report on the synthesis and self‐assembly in water of well‐defined amphiphilic star‐block copolymers with a linear crystalline polyethylene (PE) segment and two or three poly(ethylene glycol) (PEG) segments as the building blocks. Initially, alkynyl‐terminated PE (PE‐?) is synthesized via esterification of pentynoic acid with hydroxyl‐terminated PE, which is prepared using chain shuttling ethylene polymerization with 2,6‐bis[1‐(2,6‐dimethylphenyl) imino ethyl] pyridine iron (II) dichloride/methylaluminoxane/diethyl zinc and subsequent in situ oxidation with oxygen. Then diazido‐ and triazido‐terminated PE (PE‐(N₃)₂ and PE‐(N₃)₃) are obtained by the click reactions between PE‐? and coupling agents containing triazido or tetraazido, respectively. Finally, the three‐arm and four‐arm star‐block copolymers, PE‐b‐(PEG)₂ and PE‐b‐(PEG)₃, are prepared by click reactions between PE‐(N₃)₂ or PE‐(N₃)₃ and alkynyl‐terminated PEG. The self‐assembly of the resultant amphiphilic star‐block copolymers in water was investigated by dynamic light scattering, transmission electron microscopy, and atomic force microscopy. It is found that, in water, a solvent selectively good for PEG blocks; these star‐block copolymer chains could self‐assemble to form platelet‐like micelles with insoluble PE blocks as crystalline core and soluble PEG blocks as shell. The confined crystallization of PE blocks in self‐assembled structure formed in aqueous solution is investigated by differential scanning calorimetry. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Biodegradable and photocurable multiblock copolymers with shape‐memory properties from poly(ε‐caprolactone) diol,poly(ethylene glycol), and 5‐cinnamoyloxyisophthalic acid

Biodegradable and photocurable multiblock copolymers of various compositions were synthesized by the high‐temperature solution polycondensation of poly(ε‐caprolactone) (PCL) diols of molecular weight (M_n) = 3000 and poly(ethylene glycol)s (PEG) of M_n = 3000 with a dichloride of 5‐cinnamoyloxyisophthalic acid (ICA) as a chain extender, followed by irradiation by a 400 W high‐pressure mercury lamp (λ > 280 nm) to form a network structure. The gel contents increased with photocuring time, reaching a level of over 90% after 10 min for all copolymers without a photoinitiator. The thermal and mechanical properties of the photocured copolymers were examined by DSC and tensile tests. In cyclic thermomechanical tensile tests, the photocured ICA/PCL/PEG copolymer films showed good shape‐memory properties at 37–60°C, with both shape fixity ratio and shape recovery ratio over 90% at a maximum tensile strain of 100–300%. The water absorption of these copolymers and their rate of degradation in a phosphate buffer solution (pH 7.0) at 37°C increased significantly with increasing PEG content. The novel photocured ICA/PCL/PEG multiblock copolymers are potentially useful in biomedical applications. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011