Biocompatibility evaluation of self‐assembled micelles prepared from poly(lactide‐co‐glycolide)‐poly(ethylene glycol) diblock copolymers

In this work, a series of PLGA‐PEG diblock copolymers were synthesized by ring‐opening polymerization of L‐lactide and glycolide using mPEG as macroinitiator and stannous octoate as catalyst. Spherical micelles were obtained from the various copolymers by using co‐solvent evaporation method. The biocompatibility of micelles was evaluated with the aim of assessing their potential in the development of drug delivery systems. Various aspects of biocompatibility were considered, including MTT assay, agar diffusion test, release of cytokines, hemolytic test, dynamic clotting time, protein adsorption in vitro, and zebrafish embryonic compatibility in vivo. The combined results revealed that the micelles present good cytocompatibility and hemocompatibility in vitro. Moreover, the cumulative effects of micelles throughout embryos developing stages have no toxicity in vivo. It is thus concluded that micelles prepared from PLGA‐PEG copolymers present good biocompatibility as potential drug carrier.     

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

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

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

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

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

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

Synthesis of four‐armed poly(ε‐caprolactone)‐block‐poly(ethylene oxide) by diethylzinc catalyst

Biodegradable, amphiphilic, four‐armed poly(?‐caprolactone)‐block‐poly(ethylene oxide) (PCL‐b‐PEO) copolymers were synthesized by ring‐opening polymerization of ethylene oxide in the presence of four‐armed poly(?‐caprolactone) (PCL) with terminal OH groups with diethylzinc (ZnEt₂) as a catalyst. The chemical structure of PCL‐b‐PEO copolymer was confirmed by ¹H NMR and ¹³C NMR. The hydroxyl end groups of the four‐armed PCL were successfully substituted by PEO blocks in the copolymer. The monomodal profile of molecular weight distribution by gel permeation chromatography provided further evidence for the four‐armed architecture of the copolymer. Physicochemical properties of the four‐armed block copolymers differed from their starting four‐armed PCL precursor. The melting points were between those of PCL precursor and linear poly(ethylene glycol). The length of the outer PEO blocks exhibited an obvious effect on the crystallizability of the block copolymer. The degree of swelling of the four‐armed block copolymer increased with PEO length and PEO content. The micelle formation of the four‐armed block copolymer was examined by a fluorescent probe technique, and the existence of the critical micelle concentration (cmc) confirmed the amphiphilic nature of the resulting copolymer. The cmc value increased with increasing PEO length. The absolute cmc values were higher than those for linear amphiphilic block copolymers. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 950–959, 2004     

Synthesis of end‐functionalized AB copolymers. II. Synthesis and characterization of carboxyl‐terminated poly(ethylene glycol)–poly(amino acid) block copolymers

AB block copolymers composed of hydrophilic poly(ethylene glycol) (PEG) and hydrophobic poly(amino acid) with a carboxyl group at the end of PEG were synthesized with α‐carboxylic sodium‐ω‐amino‐PEG as a macroinitiator for the ring‐opening polymerization of N‐carboxy anhydride. Characterizations by ¹H NMR, IR, and gel permeation chromatography were carried out to confirm that the diblock copolymers were formed. In aqueous media this copolymer formed self‐associated polymer micelles that have a carboxyl group on the surface. The carboxyl groups located at the outer shell of the polymeric micelle were expected to combine with ligands to target specific cell populations. The diameter of the polymer micelles was in the range of 30–80 nm. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 3527–3536, 2004     

Synthesis and micellization of amphiphilic poly(sebacic anhydride)–poly(ethylene glycol)–poly(sebacic anhydride) block copolymers

Amphiphilic biodegradable block copolymers [poly(sebacic anhydride)–poly(ethylene glycol)–poly(sebacic anhydride)] were synthesized by the melt polycondensation of poly(ethylene glycol) and sebacic anhydride prepolymers. The chemical structure, crystalline nature, and phase behavior of the resulting copolymers were characterized with ¹H NMR, Fourier transform infrared, gel permeation chromatography, and differential scanning calorimetry. Microphase separation of the copolymers occurred, and the crystallinity of the poly(sebacic anhydride) (PSA) blocks diminished when the sebacic anhydride unit content in the copolymer was only 21.6%. ¹H NMR spectra carried out in CDCl₃ and D₂O were used to demonstrate the existence of hydrophobic PSA domains as the core of the micelle. In aqueous media, the copolymers formed micelles after precipitation from water‐miscible solvents. The effects on the micelle sizes due to the micelle preparation conditions, such as the organic phase, dropping rate of the polymer organic solution into the aqueous phase, and copolymer concentrations in the organic phase, were studied. There was an increase in the micelle size as the molecular weight of the PSA block was increased. The diameters of the copolymer micelles were also found to increase as the concentration of the copolymer dissolved in the organic phase was increased, and the dependence of the micelle diameters on the concentration of the copolymer varied with the copolymer composition. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 1271–1278, 2006     

Synthesis and characterization of biodegradable A–B–A triblock copolymers containing poly(ϵ‐caprolactone) A blocks and poly(trans‐4‐hydroxy‐L‐proline) B blocks

Novel, biodegradable poly(?‐caprolactone)‐block‐poly(trans‐4‐hydroxy‐N‐benzyloxycarbonyl‐L ‐proline)‐block‐poly(?‐caprolactone) triblock copolymers were synthesized by ring‐opening polymerization from dihydroxyl‐terminated macroinitiator poly(trans‐4‐hydroxy‐N‐benzyloxycarbonyl‐L ‐proline) (PHpr) and ?‐caprolactone (?‐CL) with stannous octoate as the catalyst. The molecular weights were characterized with gel permeation chromatography and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry. With an increase in the contents of ?‐CL incorporated into the copolymers, a decrease in the glass‐transition temperature (T_g) was observed. The T_g values of copoly(4‐phenyl‐?‐caprolactone) and copoly(4‐methyl‐?‐caprolactone) were higher than T_g of copoly(?‐caprolactone). Their micellar characteristics in an aqueous phase were investigated with fluorescence spectroscopy, dynamic light scattering, and transmission electron microscopy. The block copolymers formed micelles in the aqueous phase with critical micelle concentrations in the range of 1.00–1.36 mg L^?1. With higher molecular weights and hydrophobic components in the copolymers, a higher critical micelle concentration was observed. As the feed weight ratio of antitriptyline hydrochloride (AM) to the polymer increased, the drug loading increased. The micelles exhibited a spherical shape, and the average size was less than 250 nm. The in vitro hydrolytic degradation and controlled drug release properties of the triblock copolymers were also investigated. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 4268–4280, 2006     

Pendant groups fine‐tuning thermal gelation of poly(ε‐caprolactone)‐b‐poly(ethylene glycol)‐b‐poly(ε‐caprolactone) aqueous solution

Novel poly(ε‐caprolactone)‐b‐poly(ethylene glycol)‐b‐poly(ε‐caprolactone) (PCL‐PEG‐PCL) bearing pendant hydrophobic γ‐(carbamic acid benzyl ester) groups (PECB) and hydrophiphilic amino groups (PECN) were synthesized based on the functionalized comonomer γ‐(carbamic acid benzyl ester)‐ε‐caprolactone (CABCL). The thermal gelation behavior of the amphiphilic copolymer aqueous solutions was examined. The phase transition behavior could be finely tuned via the pendant groups, and an abnormal phenomenon occurred that the sol–gel transition temperature shifted to a higher temperature for PECB whereas a lower temperature for PECN. The micelles percolation was adopted to clarify the hydrogel mechanism, and the effect of the pendant groups on the micellization was further investigated in detail. The results demonstrated that the introduction of γ‐(carbamic acid benzyl ester) pendant groups significantly decreased the crystallinity of the copolymer micelles whereas amino pendant groups made the micelles easy to aggregate. Thus, the thermal gelation of PEG/PCL aqueous solution could be finely tuned by the pendant groups, and the pendant groups modified PEG/PCL hydrogels are expected to have great potential biomedical application. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 2571–2581     

Poly(ϵ‐caprolactone‐b‐glycolide) and poly(D,L‐lactide‐b‐glycolide) diblock copolyesters: Controlled synthesis,characterization, and colloidal dispersions

Living ω‐aluminum alkoxide poly‐ϵ‐caprolactone and poly‐D,L ‐lactide chains were synthesized by the ring‐opening polymerization of ϵ‐caprolactone (ϵ‐CL) and D,L ‐lactide (D,L ‐LA), respectively, and were used as macroinitiators for glycolide (GA) polymerization in tetrahydrofuran at 40 °C. The P(CL‐b‐GA) and P(LA‐b‐GA) diblock copolymers that formed were fractionated by the use of a selective solvent for each block and were characterized by ¹H NMR spectroscopy and differential scanning calorimetry analysis. The livingness of the operative coordination–insertion mechanism is responsible for the control of the copolyester composition, the length of the blocks, and, ultimately, the thermal behavior. Because of the inherent insolubility of the polyglycolide blocks, microphase separation occurs during the course of the sequential polymerization, resulting in a stable, colloidal, nonaqueous copolymer dispersion, as confirmed by photon correlation spectroscopy. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 294–306, 2001     

Copolymer of star poly(epsilon‐caprolactone) and polyglycidols as potential carriers for hydrophobic drugs

Amphiphilic star shape poly(ε‐caprolactone)‐b‐hyperbranched polyglycidol (sPCL‐HPG) were synthesized and used to investigate micell formation and to encapsulate hydrophobic drugs. The synthesis of sPCL‐HPG copolymers was carried out by using sPCL as macroinitiator for the ensuing of hypergrafting reaction with glycidols. ¹H‐NMR and FTIR were used to characterize sPCL‐b‐HPG structures. The self‐assembled structure of the sPCL‐HPG was characterized by scanning electronic microscopy (SEM), transmission electron microscopy (TEM), and atomic force microscopy (AFM). The size and size dispersities of micelles were measured by dynamic light scattering DLS. Critical micelle concentration (CMC) was determined using pyrene as fluorescent probe. Hydrophobic methyl red was encapsulated in sPCL‐HPG micelles to illustrate hydrophobic drug loading. The copolymer micelles were used to enhance paclitaxel solubility. The results showed that hydrophobic drugs could be encapsulated in the sPCL‐HPG micelles. The paclitaxel solubility in the micelles of 5 wt% of sPCL23‐HPG170 got to 168 µg/ml. sPCL‐HPG, which have biodegrability and hydrophobicity at PCL part and smaller size of HPG fragments while maintaining the total repeating units of glycidols, provide an alternative choice of carriers for poorly soluble drugs. Copyright © 2011 John Wiley & Sons, Ltd.     

Hyperbranched poly (amine‐ester)‐poly (lactide‐co‐glycolide) copolymer and their nanoparticles as paclitaxel delivery system

A new hyperbranched poly (amine‐ester)‐poly (lactide‐co‐glycolide) copolymer (HPAE‐co‐PLGA) was synthesized by ring‐opening polymerization of D , L ‐lactide (DLLA) glycolid and branched poly (amine‐ester) (HPAE‐OHs) with Sn(Oct)₂ as catalyst. The chemical structures of copolymers were determined by FT‐IR, ¹H‐NMR(¹³C NMR), TGA and their molecular weights were determined by gel permeation chromatography (GPC). Paclitaxel‐loaded copolymer nanoparticles were prepared by the nanoprecipitation method. Their physicochemical characteristics, e.g. morphology and nanoparticles size distribution were then evaluated by means of fluorescence spectroscopy, environmental scanning electron microscopy (ESEM), and dynamic light scattering (DLS). Paclitaxel‐loaded nanoparticles assumed a spherical shape and have unimodal size distribution. It was found that the chemical composition of the nanoparticles was a key factor in controlling nanoparticles size, drug‐loading content, and drug release behavior. As the molar ratio of DL ‐lactide/glycolide to HPAE increased, the nanoparticles size and drug‐loading content increased, and the drug release rate decreased. The antitumor activity of the paclitaxel‐loaded HPAE‐co‐PLGA nanoparticles against human liver cancer H7402 cells was evaluated by 3‐(4, 5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) method. The paclitaxel‐loaded HPAE‐co‐PLGA nanoparticles showed comparable anticancer efficacy with the free drug. Copyright © 2010 John Wiley & Sons, Ltd.     

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

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

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 a biodegradable amphiphilic copolymer based on branched poly(ϵ‐caprolactone) and poly(ethylene glycol)

A novel biodegradable amphiphilic copolymer with hydrophobic poly(ε‐caprolactone) branches containing cholic acid moiety and a hydrophilic poly(ethylene glycol) chain was synthesized. The copolymer was characterized by FTIR, ¹H NMR, gel permeation chromatography (GPC), differential scanning calorimetry (DSC), polarizing light microscopy (PLM), and wide‐angle X‐ray diffraction (WAXD) analysis. The amphiphilic copolymer could self‐assemble into micelles in an aqueous solution. The critical micelle concentration of the amphiphilic copolymer was determined by fluorescence spectroscopy. A nanoparticle drug delivery system with a regularly spherical shape was prepared with high encapsulation efficiency. The in vitro drug release from the drug‐loaded polymeric nanoparticles was investigated. Because of the branched structure of the hydrophobic part of the copolymer and the relatively fast degradation rate of the copolymer, an improved release behavior was observed. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5256–5265, 2007     

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     

Phase‐transition characteristics of amphiphilic poly(2‐ethyl‐2‐oxazoline)/poly(ε‐caprolactone) block copolymers in aqueous solutions

Amphiphilic diblock and triblock copolymers of various block compositions based on hydrophilic poly(2‐ethyl‐2‐oxazoline) (PEtOz) and hydrophobic poly(ε‐caprolactone) were synthesized. The micelle formation of these block copolymers in aqueous media was confirmed by a fluorescence technique and dynamic light scattering. The critical micelle concentrations ranged from 35.5 to 4.6 mg/L for diblock copolymers and 4.7 to 9.0 mg/L for triblock copolymers, depending on the block composition. The phase‐transition behaviors of the block copolymers in concentrated aqueous solutions were investigated. When the temperature was increased, aqueous solutions of diblock and triblock copolymers exhibited gel–sol transition and precipitation, both of which were thermally reversible. The gel–sol transition‐ and precipitation temperatures were manipulated by adjustment of the block composition. As the hydrophobic portion of block copolymers became higher, a larger gel region was generated. In the presence of sodium chloride, the phase transitions were shifted to a lower temperature level. Sodium thiocyanate displaced the gel region and precipitation temperatures to a higher temperature level. The low molecular weight saccharides, such as glucose and maltose, contributed to the shift of phase‐transition temperatures to a lower temperature level, where glucose was more effective than maltose in lowering the gel–sol transition temperatures. The malonic acid that formed hydrogen bonds with the PEtOz shell of micelles was effective in lowering phase‐transition temperatures to 1.0M, above which concentration the block copolymer solutions formed complex precipitates. © 2000 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 38: 2400–2408, 2000     

Methoxy poly(ethylene glycol)‐b‐poly(octadecanoic anhydride)‐b‐methoxy poly(ethylene glycol) amphiphilic triblock copolymer nanoparticles as delivery vehicles for paclitaxel

A series of amphiphilic triblock copolymers, methoxy poly(ethylene glycol)‐b‐poly(octadecanoic anhydride)‐b‐methoxy poly(ethylene glycol) (mPEG‐b‐POA‐b‐mPEG), were prepared via melt polycondensation of methoxy poly(ethylene glycol) (mPEG) and poly(octadecanoic anhydride) (POA). mPEG‐b‐POA‐b‐mPEG were characterized by FTIR, ¹H‐NMR, GPC, DSC, and XRD. Drug‐loaded mPEG‐b‐POA‐b‐mPEG nanoparticles (NPs) with spherical morphology and narrow size polydispersity index were prepared by nanoprecipitation technique with paclitaxel as the model drug. In vitro release behaviors of drug‐loaded NPs present that the biphasic process and the release mechanism of each phase are zero order drug releases. According to this study, mPEG‐b‐POA‐b‐mPEG NPs could serve as suitable delivery agents for paclitaxel and other hydrophobic drugs. Copyright © 2009 John Wiley & Sons, Ltd.     

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.     

Synthesis and characterization of resorcinarene‐centered amphiphilic A8B4 miktoarm star copolymers based on poly(ε‐caprolactone) and poly(ethylene glycol) by combination of CROP and “click” chemistry

Well‐defined amphiphilic A₈B₄ miktoarm star copolymers with eight poly(ethylene glycol) chains and four poly(ε‐caprolactone) arms (R‐8PEG‐4PCL) were prepared using “click” reaction strategy and controlled ring‐opening polymerization (CROP). First, multi‐functional precursor (R‐8N₃‐4OH) with eight azides and four hydroxyls was synthesized based on the derivatization of resorcinarene. Then eight‐PEG‐arm star polymer (R‐8PEG‐4OH) was prepared through “click” reaction of R‐8N₃‐4OH with pre‐synthesized alkyne‐terminated monomethyl PEG (mPEG‐A) in the presence of CuBr/N,N,N′,N″,N″′‐ pentamethyldiethylenetriamine (PMDETA) in DMF. Finally, R‐8PEG‐4OH was used as tetrafunctional macroinitiator to prepare resorcinarene‐centered A₈B₄ miktoarm star copolymers via CROP of ε‐caprolactone utilizing Sn(Oct)₂ as catalyst at 100 °C. These miktoarm star copolymers could self‐assemble into spherical micelles in aqueous solution with resorcinarene moieties on the hydrophobic/hydrophilic interface, and the particle sizes could be controlled by the ratio of PCL to PEG. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 2824–2833.