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.     

Thermosensitive polylactide‐glycolide delivery systems for treatment of narcotic addictions

Environmental switches may be fabricated for the controlled release of pharmaceutical drug using a thermally responsive polymer with the intrinsic chemical and physical nature of stimuli‐sensitive smart materials. Particularly, much attention has been paid to the biomedical applications of poly(N‐isopropyl acrylamide) (PNIPAAm) because of its unique reversible transition at a specific lower critical solution temperature (LCST).Thermally sensitive block copolymers, poly(N‐isopropyl acrylamide‐b‐poly(L ‐lactide‐co‐glycolide) (PNIPAAm‐b‐PLGA), and polyethylene glycol‐poly (lactide‐co‐glycolide) (PEG‐PLGA) triblock copolymers with different compositions and length of PLGA block were synthesized via ring‐opening polymerization of lactide and glycolide in the presence of OH‐terminated PNIPAAm or PEG. The composition and structure of the polymer were determined by NMR and FTIR. The effect of important factors, such as ionic strength, pH, and polymer concentration on the phase transition behavior of temperature‐sensitive polymers, were investigated by cloud point measurements. The resulting thermosensitive polymers were used for the entrapment of a narcotic antagonist drug, naltrexone, as the model drug. The loading efficiency and drug release behavior of naltrexone‐loaded hydrogels were investigated. The naltrexone loaded thermosensitive polymers were able to sustain the release of naltrexone for different periods of time, depending on the polymer composition, and concentration. In vitro release studies showed that these thermosensitive polymers are able to deliver naltrexone in biologically active forms at a controlled rate for 3–8 weeks. Copyright © 2009 John Wiley & Sons, Ltd.     

Pyrogallic acid‐PLGA conjugate as new biodegradable material suitable for final sterilization by irradiation

This paper reports the feasibility to prepare a biodegradable material stable to γ‐irradiation by grafting of poly(lactide‐co‐glycolide) with pyrogallic acid (PLGA‐g‐PA) and ferulic acid (PLGA‐g‐FA) in mild condition. Only the grafting procedure with PA did not modify molecular weight (Mw) of the starting polymer and PLGA‐g‐PA showed antioxidant properties. The polymer degradation in pH 7.4 phosphate buffer saline (PBS) was mainly governed by a random chain scission mechanism according to a first‐order reaction. The irradiation at the dose of 25 kGy caused only a very slight decrease of Mw and the degradation patterns of the non‐irradiated and irradiated material were superimposable. PLGA‐g‐PA resulted a promising material to develop biodegradable drug delivery systems which would be sterilizable in the final container. Copyright © 2010 John Wiley & Sons, Ltd.     

Synthesis and characterization of a series of biodegradable and biocompatible PEG‐supported poly(lactic‐ran‐glycolic acid) amphiphilic barbell‐like copolymers

A series of multihydroxyl (2, 4, and 8) terminated poly(ethylene glycol)s and their biodegradable, biocompatible, and branched barbell‐like (PLGA)_n‐b‐PEG‐b‐(PLGA)_n (n = 1, 2, 4) copolymers have been synthesized. The lengths of the PLGA arms were varied by controlling the molar ratio of monomers to hydroxyl groups of PEG ([LA+GA]₀/[? OH]₀ = 23, 45, 90). Chemical structures of synthesized barbell‐like copolymers were confirmed by both ¹H and ¹³C‐NMR spectroscopies. Molecular weights were determined by ¹H‐NMR end‐group analysis and gel permeation chromatography. The result of hydrolytic degradation indicated that the rate of degradation increased with the increase of arm numbers or with the decrease of arm lengths. The thermal properties were evaluated by using differential scanning calorimetry and a thermogravimetric analysis. The results indicated that the thermal properties of barbell‐like copolymers depended on the structural variations. The morphology of (PLGA)_n‐PEG‐(PLGA)_n copolymers self‐assembly films were investigated by atomic force microscope, the results indicated that the microphase separation existed in (PLGA)_n‐PEG‐(PLGA)_n copolymers. Because of the favorable biodegradability and biocompatibility of the PLGA and PEG, these results may therefore create new possibilities for these novel structural amphiphilic barbell‐like copolymers as potential biomaterials. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 3802–3812, 2008     

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     

Effect of PLGA block molecular weight on gelling temperature of PLGA‐PEG‐PLGA thermoresponsive copolymers

Thermoresponsive, biodegradable polymeric hydrogel networks are used widely in medicinal applications. Poly(d ,l ‐lactic acid‐co‐glycolic acid)‐b‐poly(ethylene glycol)‐b‐poly(d ,l ‐lactic acid‐co‐glycolic acid) (PLGA‐PEG‐PLGA) triblock copolymers exhibit a sol–gel transition upon heating. The effect of PLGA block and PEG chain molecular weights (MWs) on the gelling temperature of polymer aqueous solution (20% w/w) is described. All polymer solutions convert into a hard gel within 2 °C of the gelling temperature. The release properties of the gels were displayed using paracetamol as a representative drug. A linear relation is described between the gelling temperature and PLGA block MW. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019 , 57, 35–39     

N‐Boc‐Histidine‐Capped PLGA‐PEG‐PLGA as a Smart Polymer for Drug Delivery Sensitive to Tumor Extracellular pH

A pH‐sensitive polymer was synthesized by introducing the N‐Boc‐histidine to the ends of a PLGA‐PEG‐PLGA block copolymer. The synthesized polymer was confirmed to be biodegradable and biocompatible, well dissolved in water and forming micelles above the CMC. DOX was employed as a model anticancer drug. In vitro drug release from micelles of N‐Boc‐histidine‐capped PLGA‐PEG‐PLGA exhibited significant difference between pH = 6.2 and pH = 7.4, whereas DOX release from micelles composed of un‐capped virgin polymers was not significantly sensitive to medium pH. Uptake of DOX from micelles of the new polymer into MDA‐MB‐435 solid tumor cells was also observed, and pH sensitivity was confirmed. Hence, the N‐Boc‐histidine capped PLGA‐PEG‐PLGA might be a promising material for tumor targeting.

     

Highly porous poly(lactide‐co‐glycolide) microparticles for sustained tiotropium release

In this study, porous poly(lactide‐co‐glycolide) (PLGA) microparticles with low mass density and large particle size were developed for chronic obstructive pulmonary disease treatment using anticholinergic drug (tiotropium). The porous PLGA microparticles were prepared by the water‐in‐oil‐in‐water (W₁/O/W₂) multi‐emulsion method using PLGA polymer and ammonium bicarbonate (as a porogen). Herein, soluble starch was incorporated in porous PLGA microparticles for long‐term tiotropium release. In vitro drug release studies determined that the rapid release of tiotropium from porous PLGA microparticles was reduced because of the high viscosity of the incorporated starch. Tiotropium release from porous PLGA microparticles continued up to 3 days. Furthermore, the inhaled microparticles showed longer drug residence in in vivo lung epithelium. Copyright © 2013 John Wiley & Sons, Ltd.     

Bioreducible and core‐crosslinked hybrid micelles from trimethoxysilyl‐ended poly(ε‐caprolactone)‐S‐S‐poly(ethylene oxide) block copolymers: Thiol‐ene click synthesis and properties

Bioreducible and core‐crosslinked hybrid micelles were for the first time fabricated from biodegradable and biocompatible trimethoxysilyl‐terminated and disulfide‐bond‐linked block copolymers poly(ε‐caprolactone)‐S‐S‐poly(ethylene oxide), which were prepared by combining thiol‐ene coupling reaction and ring‐opening polymerization. The molecular structures, physicochemical, self‐assembly, and bioreducible properties of these copolymers were thoroughly characterized by means of FTIR, ¹H NMR, gel permeation chromatography, differential scanning calorimetry, wide‐angle X‐ray diffraction, dynamic light scattering (DLS), and transmission electron microscopy. The core‐crosslinking sol‐gel reaction was confirmed by ¹H NMR, and the core‐crosslinked hybrid micelles contained about 3 wt % of silica. The bioreducible property of both uncrosslinked and core‐crosslinked micelles in 10 mM 1,4‐dithiothreitol (DTT) solution was monitored by DLS, which demonstrated that the PEO corona gradually shedded from the PCL core. The anticancer doxorubicin drug‐loaded micelles showed nearly spherical morphology compared with blank micelles, presenting a DTT reduction‐triggered drug‐release profile at 37 °C. Notably, the core‐crosslinked hybrid micelles showed about twofold drug loading capacities and a half drug‐release rate compared with the uncross‐liked counterparts. This work provides a useful platform for the fabrication of bioreducible and core‐crosslinked hybrid micelles potential for anticancer drug delivery system. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

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     

Solid‐State NMR investigations of anhydrous proton‐conducting acid–base poly(acrylic acid)– poly(4‐vinyl pyridine) polymer blend system: A study of hydrogen bonding and proton conduction

NMR studies of the structure and dynamics of a system composed of the acidic polymer poly(acrylic acid) (PAA) and the basic polymer poly(4‐vinyl pyridine) (P4VP) are presented. This system aims at the application of anhydrous proton‐conducting membranes that can be used at elevated temperatures at which the proton conduction of hydrated membranes breaks down. The ¹H NMR measurements have been preformed under fast magic angle spinning (MAS) conditions to achieve sufficient resolution and the applied ¹H NMR methods vary from simple ¹H MAS to double‐quantum filtered methods and two‐dimensional ¹H double‐quantum spectroscopy. The dynamic behavior of the systems has been investigated via variable temperature ¹H MAS NMR. ¹³C cross‐polarization MAS NMR provides additional aspects of dynamic and structural features to complete the picture. Different types of acidic protons have been identified in the studied PAA‐P4VP systems that are nonhydrogen‐bonded free acidic protons, hydrogen‐bonded dicarboxylic dimers, and protons forming hydrogen bonds between carboxylic protons and ring nitrogens. The conversion of dimer structures in dried PAA to free carboxylic acid groups is accomplished at temperatures above 380 K. However, the stability of hydrogen‐bonding strongly depends on the hydration level of the polymer systems. The effect of hydration becomes less apparent in the complexes. An inverse proportionality between hydrogen‐bonding strength and proton conduction in the PAA‐P4VP acid–base polymer blend systems was established. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 47: 138–155, 2009     

Synthesis of an esterase‐sensitive degradable polyester as facile drug carrier for cancer therapy

Polyethylene glycol (PEG) is widely used as a carrier to improve the pharmaceutical properties of drugs with low molecular weight. However, PEG has few functional groups (usually two) for drug conjugation and the resulting low drug content (1–2%) has hampered its clinical applications. For this study, we synthesized biodegradable poly(ethylene glycol‐co‐anhydride). This polyester‐based polymer possesses multiple carboxylic acid groups that can be used as facile drug carriers. Two anticancer drugs, camptothecin (CPT) and doxorubicin (DOX) were loaded into the carrier and their releasing properties and in vitro anticancer activities were studied. The polymer–drug conjugates exhibited esterase‐promoted degradation and drug release. Their cytotoxicity against the human ovarian cancer cell line SKOV‐3 was comparable to unconjugated drugs. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 507–515     

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     

Synthesis of star‐shaped poly(D,L‐lactic acid‐alt‐glycolic acid)‐b‐poly(L‐lactic acid) with the poly(D,L‐lactic acid‐alt‐glycolic acid) macroinitiator and stannous octoate catalyst

Two types of three‐arm and four‐arm, star‐shaped poly(D,L ‐lactic acid‐alt‐glycolic acid)‐b‐poly(L ‐lactic acid) (D,L ‐PLGA50‐b‐PLLA) were successfully synthesized via the sequential ring‐opening polymerization of D,L ‐3‐methylglycolide (MG) and L ‐lactide (L ‐LA) with a multifunctional initiator, such as trimethylolpropane and pentaerythritol, and stannous octoate (SnOct₂) as a catalyst. Star‐shaped, hydroxy‐terminated poly(D,L ‐lactic acid‐alt‐glycolic acid) (D,L ‐PLGA50) obtained from the polymerization of MG was used as a macroinitiator to initiate the block polymerization of L ‐LA with the SnOct₂ catalyst in bulk at 130 °C. For the polymerization of L ‐LA with the three‐arm, star‐shaped D,L ‐PLGA50 macroinitiator (number‐average molecular weight = 6800) and the SnOct₂ catalyst, the molecular weight of the resulting D,L ‐PLGA50‐b‐PLLA polymer linearly increased from 12,600 to 27,400 with the increasing molar ratio (1:1 to 3:1) of L ‐LA to MG, and the molecular weight distribution was rather narrow (weight‐average molecular weight/number‐average molecular weight = 1.09–1.15). The ¹H NMR spectrum of the D,L ‐PLGA50‐b‐PLLA block copolymer showed that the molecular weight and unit composition of the block copolymer were controlled by the molar ratio of L ‐LA to the macroinitiator. The ¹³C NMR spectrum of the block copolymer clearly showed its diblock structures, that is, D,L ‐PLGA50 as the first block and poly(L ‐lactic acid) as the second block. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 40: 409–415, 2002     

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.     

Hydrogen‐bonding‐aided synthesis of novel ladderlike organobridged polysiloxane containing side‐chain naphthyl groups

With a hydrogen‐bonding template, a novel soluble aryl amide‐bridged ladderlike polysiloxane, containing naphthyl as the side‐chain group, has been successfully synthesized via a stepwise coupling polymerization. It is proposed that the monomer, N,N′‐di(3‐naphthyldiethoxylsilyl‐propyl)‐[4,4′‐oxybis(benzyl amide)], prepared by Grignard and hydrosilylation reactions, undergoes self‐assembly first via amido hydrogen bonding and then via hydrolysis, followed by condensation under controlled reaction conditions to yield a high molecular weight, soluble, dark yellow polymer. The analytical results (Fourier transform infrared, ¹H NMR, ²⁹Si NMR, X‐ray diffraction, differential scanning calorimetry, and vapor pressure osmometry) show that the polymer possesses an ordered ladderlike architecture. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 636–644, 2003     

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     

Novel ‘Nano in Nano’ Composites for Sustained Drug Delivery: Biodegradable Nanoparticles Encapsulated into Nanofiber Non‐Wovens

Novel ‘nano in nano’ composites consisting of biodegradable polymer nanoparticles incorporated into polymer nanofibers may efficiently modulate drug delivery. This is shown here using a combination of model compound‐loaded biodegradable nanoparticles encapsulated in electrospun fibers. The dye coumarin 6 is used as model compound for a drug in order to simulate drug release from loaded poly(lactide‐co‐glycolide) nanoparticles. Dye release from the nanoparticles occurs immediately in aqueous solution. Dye‐loaded nanoparticles which are encapsulated by electrospun polymer nanofibers display a significantly retarded release.

     

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

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

Disulfide‐centered star‐shaped polypeptide‐PEO block copolymers for reduction‐triggered drug release

Disulfide‐centered star‐shaped poly(ε‐benzyloxycarbonyl‐l ‐lysine)‐b‐poly(ethylene oxide) block copolymers (i.e., A₂B₄ type Cy‐PZlys‐b‐PEO) were synthesized by the combination of ring‐opening polymerization and thiol‐yne chemistry. Their molecular structures and physical properties were characterized in detail by FTIR, ¹H NMR, gel permeation chromatography, differential scanning calorimetry, wide‐angle X‐ray diffraction, and polarized optical microscope. Despite mainly exhibiting an α‐helix conformation, the inner PZlys blocks within copolymers greatly prohibited the crystallinity of the outer PEO blocks and presented a liquid crystal phase transition behavior in solid state. These block copolymers Cy‐PZlys‐b‐PEO self‐assembled into nearly spherical micelles in aqueous solution, which had a hydrophobic disulfide‐centered PZlys core surrounded by a hydrophilic PEO corona. As monitored by means of DLS and TEM, these micelles were progressively reduced to smaller micelles in 10 mM 1,4‐dithiothreitol at 37 °C and finally became ones with a half size, demonstrating a reduction‐sensitivity. Despite a good drug‐loading property, the DOX‐loaded micelles of Cy‐PZlys‐b‐PEO exhibited a reduction‐triggered drug release profile with an improved burst‐release behavior compared with the linear counterpart. Importantly, this work provides a versatile strategy for the synthesis of the disulfide‐centered star‐shaped polypeptide block copolymers potential for intracellular glutathione‐triggered drug delivery systems. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 2000–2010