Polyampholyte Nanoparticles Prepared by Self‐Complexation of Cationized Poly(γ‐glutamic acid) for Protein Carriers

A novel amphoteric poly(amino acid) is synthesized by grafting a cationic amino acid (L ‐Arg) to γ‐PGA to prepare charged NPs. γ‐PGA‐Arg NPs can be prepared by the self‐complexation of a single polymer by intra‐/inter‐molecular electrostatic interactions when the polymer is dispersed in water. The size and surface charge of the NPs can be regulated by the grafting degree of Arg (41, 56, and 83%). The smallest NPs are obtained at 56% grafting degree of the γ‐PGA‐Arg copolymer. The 56 and 83% grafting degree NPs are stable for at least 1 week. Depending on their surface charge, these NPs can selectively adsorb anionically or cationically charged proteins.

     

Investigation on thermoresponsive behavior of biodegradable poly(γ‐glutamic acid)‐graft‐L‐phenylalanine ethyl ester

The thermosensitivity of biodegradable and non‐toxic amphiphilic polymer derived from a naturally occurring polypeptide and a derivative of amino acid was first reported. The amphiphilic polymer consisted of poly(γ‐glutamic acid) (γ‐PGA) as a hydrophilic backbone, and L ‐phenylalanine ethyl ester (L ‐PAE) as a hydrophobic branch. Poly(γ‐glutamic acid)‐graft‐L ‐phenylalanine (γ‐PGA‐graft‐L ‐PAE) with grafting degrees of 7–49% were prepared by varying the content of a water‐soluble carbodiimide (WSC). γ‐PGA‐graft‐L ‐PAE with a grafting degree of 49% exhibited thermoresponsive phase transition behavior in an aqueous solution at around 80°C. The copolymers with grafting degrees in the range of 30–49% showed thermoresponsive properties in NaCl solution. A clouding temperature (T_cloud) could be adjusted by changing the polymer concentration and/or NaCl concentration. The thermoresponsive behavior was reversible. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Visualization of spontaneous aggregates by diblock poly(styrene)‐b‐poly(L‐lactide)/poly(D‐lactide) pairs in solution with new fluorescent CdSe quantum dot labels

Spontaneous stereocomplex aggregation of diblock poly(styrene)‐b‐poly(L ‐lactide) PS‐b‐PLLA/poly(D ‐lactide) PDLA pairs has been investigated under ambient temperature in tetrahydrofuran solution. First, diblock PS₂₆₀‐b‐PLLA₁₆₅ and PS₂₆₀‐b‐PDLA₁₆₂ bearing similar lengths of respective PLLA and PDLA blocks were synthesized through controlled atom‐transfer radical polymerization of styrene, and a subsequent living ring‐opening polymerization of optically pure lactides, and their structures were further characterized by nuclear magnetic resonance spectroscopy (NMR) and gel‐permeation chromatography (GPC). Subsequently, new enantiomeric poly(D ‐lactide) stabilized core‐shell fluorescent CdSe quantum dots (CdSe/PDLA QD) were designed and prepared as sensitive fluorescence labels to shed new lights on the spontaneous stereocomplex aggregation in THF, which was mediated by stereocomplexation of the PLLA and PDLA chains. Upon simply mixing two individual THF solution of diblock PS₂₆₀‐b‐PLLA₁₆₅ and HO‐PDLA₃₀‐SH, spontaneous stereocomplex aggregation was studied, and the aggregated uniform spherical particles were observed by scanning electronic microscopy (SEM) to exhibit average particle diameters of 2.0 μm. Finally, utilizing the prepared CdSe/PDLA QDs as new fluorescent labels, morphologies of the spontaneous aggregates by new diblock PS₂₆₀‐b‐PLLA₁₆₅/HO‐PDLA₃₀‐SH pair were for the first time directly visualized by a confocal laser scanning fluorescence microscopy (CLSFM). These results might suggest alternative ways to simply prepare functional fluorescent particles with tunable diameter sizes and would be helpful to understand the mechanism of stereocomplex particle aggregation. © 2009 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 47: 1393–1405, 2009     

Preparation of Pixantrone/Poly(γ‐glutamic acid) Nanoparticles through Complex Self‐Assembly for Oral Chemotherapy

A facile and green approach is reported to construct pixantrone/poly(γ‐glutamic acid) nanoparticles (PIX/γ‐PGA NPs) as an oral drug delivery system through the complex self‐assembly of polyelectrolyte γ‐PGA and the anticancer drug pixantrone dimaleate (PDM). The complex self‐assembly behavior is investigated in detail. The results demonstrate that PDM can interact with γ‐PGA to conveniently form NPs and the size of NPs can be controlled by adjusting the solution volume ratio of PDM to γ‐PGA. These NPs illustrate their pH‐dependent release behavior, efficient cellular uptake and enhanced drug efficacy through an in vitro release study, flow cytometry, CLSM analysis and the MTT assay. In summary, PIX/γ‐PGA NPs may serve as a promising oral drug delivery system for cancer therapy.

     

Self‐Assembly in Water of Poly(acrylic acid)‐Based Diblock Copolymers Synthesized by Nitroxide‐Mediated Polymerization

Summary: Amphiphilic diblock copolymers consisting of a hydrophilic block, poly(acrylic acid), and a hydrophobic block, polystyrene, were synthesized by direct nitroxide‐mediated polymerization using the PS block as a macro‐initiator for the first time. Several techniques were used to characterize the amphiphilic block copolymers (size exclusion chromatography, NMR spectroscopy). The proposed method can lead to samples with a broad range of composition and molar mass. Preliminary studies of their self‐assembly in aqueous medium using fluorescence spectroscopy and small‐angle neutron scattering are presented.

Schematic of the formation of the PS‐b‐PAA block copolymers and their micellization in aqueous media.     

Linear and four‐armed poly(l‐lactide)‐block‐poly(d‐lactide) copolymers and their stereocomplexation with poly(lactide)s

Linear and four‐armed poly(l ‐lactide)‐block‐poly(d ‐lactide) (PLLA‐b‐PDLA) block copolymers are synthesized by ring‐opening polymerization of d ‐lactide on the end hydroxyl of linear and four‐armed PLLA prepolymers. DSC results indicate that the melting temperature and melting enthalpies of poly (lactide) stereocomplex in the copolymers are obviously lower than corresponding linear and four‐armed PLLA/PDLA blends. Compared with the four‐armed PLLA‐b‐PDLA copolymer, the similar linear PLLA‐b‐PDLA shows higher melting temperature (212.3 °C) and larger melting enthalpy (70.6 J g^?1). After these copolymers blend with additional neat PLAs, DSC, and WAXD results show that the stereocomplex formation between free PLA molecular chain and enantiomeric PLA block is the major stereocomplex formation. In the linear copolymer/linear PLA blends, the stereocomplex crystallites (sc) as well as homochiral crystallites (hc) form in the copolymer/PLA cast films. However, in the four‐armed copolymer/linear PLA blends, both sc and hc develop in the four‐armed PLLA‐b‐PDLA/PDLA specimen, which means that the stereocomplexation mainly forms between free PDLA molecule and the inside PLLA block, and the outside PDLA block could form some microcrystallites. Although the melting enthalpies of stereocomplexes in the blends are smaller than that of neat copolymers, only two‐thirds of the molecular chains participate in the stereocomplex formation, and the crystallization efficiency strengthens. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2014 , 52, 1560–1567     

Stereocomplex formation between enantiomeric poly(α‐methyl‐α‐ethyl‐β‐propiolactones): Effect of molecular weight

Optically pure S(?) and R(+)‐poly(α‐methyl‐α‐ethyl‐β‐propiolactones) (PMEPLs) of controlled low molecular weights were synthesized by anionic polymerization of the corresponding optically active monomers, and characterized using gel permeation chromatography, Maldi‐TOF mass spectrometry, and NMR spectroscopy. Blends of PMEPLs of opposite configurations and different molecular weights were investigated. All blends lead to the formation of a stereocomplex and its crystallization prevails over a wide range of mixing ratios. The stereocomplex melts 30–40 °C above that of the corresponding pure polymers, depending on the molecular weight; pairs of polymers having similar molecular weights exhibit the highest melting temperatures and enthalpies of fusion. Finally, when the stereocomplex is dispersed in a PMEPL matrix, it acts as a very effective nucleation agent for the crystallization of the polymer in excess. © 2007 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 45: 2380–2389, 2007     

Cationic Graft Copolymers as Carriers for Delivery of Antisense‐Oligonucleotides

Self‐assembling systems based on ionic complexes of DNA fragments (36 base pairs), bcl‐2 antisense oligonucleotides (octadecamer), oligophosphates (25 phosphate groups) or acrylic oligomers (18 groups of phosphonic acid) with poly(L ‐lysine) (PLL) ( = 130 000 and 88 000) grafted with short poly[N‐(2‐hydroxypropyl)methacrylamide] (PHPMA) chains ( = 4 300 or 8 600) were studied by static and dynamic light scattering methods as systems suitable for gene therapy applications. The graft copolymers (GPLLs) with shorter PHPMA grafts ( = 4 300) provide polyelectrolyte complexes (PECs) with smaller and R_H than the corresponding GPLLs with longer grafts ( = 8 600) and the same content of PLL. The lowest aggregation number of 2 was observed for PECs prepared from the GPLL with short grafts and 40 wt.‐% of PLL. The complexes of oligonucleotides and DNA fragments with GPLLs showed quite similar behavior to that with oligophosphates and acrylic oligomer. The complexes prepared from GPLLs containing 40 wt.‐% of PLL and at excess of oligophosphate were stable for at least 48 h under physiological conditions (0.15 M NaCl) and in bovine serum albumin solutions (1 mg · mL^?1). Additionally, polyanion exchange reactions of the PECs in contact with poly(styrenesulfonate) and DNA were studied in 0.15 M NaCl solutions. The oligophosphates in complexes were at least partially substituted with high‐molecular‐weight polyanions. The structure of the initial PECs dominated the PEC structure after the exchange reaction.

The dependence of the molecular weight (a) and the hydrodynamic radius R_H (b) of complexes of the oligophosphate (OPP) and four graft copolymers (GPLLi, i = 0–3) on the mixing ratio X.     

Crystallization and stereocomplexation governed self‐assembling of poly(lactide)‐b‐poly(ethylene glycol) to mesoscale structures

The stereocomplex formation between enantioselective poly(lactide) (PLA) homopolymers is well understood. In this report an attempt is made to analyze the influence on the self‐assembling of the stereocomplex of enantiomorphic PLA‐PEG di‐ and tri‐blocks in different solvents. Powder diffraction studies showed the poly(ethylene glycol) (PEG) and the PLA blocks crystallize separately forming unique supra structures like rods, discs and coiled coils with dimensions in the micrometer scale in length and sub‐micrometer scale in diameter. The influence of the solvents on the crystal formation was shown in the formation of uniform structures. Discs emerged from equimolar mixtures of the D ‐ and L ‐configured di‐ and tri‐block copolymers, in dioxan and acetonitrile and in water the stereocomplexes crystallized mainly as rods. In some cases the rods were observed as coiled coils. The shape, the hydrophobic/hydrophilic content and the PEG coated surface of the discs give them a future potential as matrix for the controlled and targeted delivery of bioactive agents. Copyright © 2005 John Wiley & Sons, Ltd.     

Novel poly(l‐lactide)/poly(d‐lactide)/poly(tetrahydrofuran) multiblock copolymers with a controlled architecture: Synthesis and characterization

Novel poly(l ‐lactide) (PLLA)/poly(d ‐lactide) (PDLA)/poly(tetrahydrofuran) (PTHF) multiblock copolymers with designed molecular structure were synthesized by a two‐stage procedure. Well‐defined PDLA‐PLLA‐PTHF‐PLLA‐PDLA pentablock copolymers were prepared by sequential ring opening polymerization of l ‐ and d ‐lactides starting from PTHF glycol, with the length of the (equimolar) PLLA and PDLA blocks being varied. Then, these dihydroxyl‐terminated pentamers were transformed into multiblock copolymers by melt chain‐extension with hexamethylene diisocyanate–being the first time that the coupling of pentablock units is reported. The successful formation of macromolecular chains with a multiblock and well‐defined architecture was demonstrated by ¹H NMR spectroscopy. The thermal properties and structuring of the resulting materials were investigated by means of DSC and WAXD measurements and DMA analysis. Stereocomplexation was found to be promoted during solution and melt crystallization. This approach affords materials combining the high rigidity and strength (other than improved thermal resistance) of the hard stereocomplex crystallites with the flexibility imparted by the soft block, whereby their properties can be finely tailored through the composition of the basic pentablock units without limitations on the final molecular weight. The adopted reaction conditions make this process highly appealing in view of the possibility to perform it in extruder. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 3269–3282     

Self‐Catalysis of Phthaloylchitosan for Graft Copolymerization of ε‐Caprolactone with Chitosan

Summary: A protection‐graft‐deprotection method was developed to prepare chitosan‐g‐polycaprolactone graft copolymers, during which the ring‐opening copolymerization of ε‐caprolactone onto phthaloylchitosan (PHCS) happened without any additional catalysis. The intermediate PHCS was introduced primarily to protect the active amino group of chitosan. After controlled experiments, the phthalimido compound was proposed to be a novel kind of organic catalyst for the ring‐opening polymerization of caprolactone monomers, while the hydroxyl group acted as an initiator. Hence, in this graft system, PHCS was endowed with both self‐catalysis and self‐initiation at the same time, and the PCL side chains grew from the hydroxyl groups of the chitosan backbone.

     

Nano Grape Formation by isotactic‐Poly(methacrylic acid)‐block‐Poly(butyl acrylate)

A novel approach is employed to produce core–corona nanospheres, which introduces a stereoregular hydrophilic part to an amphiphilic block copolymer. The resultant morphology is reported using isotactic‐poly(methacrylic acid)‐block‐poly(butyl acrylate). Infrared spectroscopy revealed a supramolecular interaction, and X ray diffraction revealed the crystallization of the outer isotactic‐poly(methacrylic acid) part. The nanostructure, which looks like a nanosized ‘grape’, was formed when nanospheres and nanofibers coexisted simultaneously and partially fused.

     

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     

Novel Amphiphilic Degradable Poly(ε‐caprolactone)‐graft‐poly(4‐vinyl pyridine), Poly(ε‐caprolactone)‐graft‐poly(dimethylaminoethyl methacrylate) and Water‐Soluble Derivatives

New amphiphilic graft copolymers that have a poly(ε‐caprolactone) (PCL) biodegradable hydrophobic backbone and poly(4‐vinylpyridine) (P4VP) or poly(2‐(N,N‐dimethylamino)ethyl methacrylate) (PDMAEMA) hydrophilic side chains have been prepared by anionic polymerization of the corresponding 4VP and DMAEMA monomers using a PCL‐based macropolycarbanion as initiator. The water solubility of these amphiphilic copolymers is improved by quaternization, which leads to fully water‐soluble cationic copolymers that give micellar aggregates in deionized water with diameters ranging from 65 to 125 nm. In addition, to improve the hydrophilicity of PCL‐g‐P4VP, grafting of poly(ethylene glycol) (PEG) segments has been carried out to give a water‐soluble double grafted PCL‐g‐(P4VP;PEG) terpolymer.

     

β‐Lactam functionalized poly(isoprene‐b‐ethylene oxide) amphiphilic block copolymers

Amphiphilic block copolymers containing β‐lactam groups on the polyisoprene block were synthesized from poly(isoprene‐b‐ethylene oxide) (IEO) diblock copolymer precursors, prepared by anionic polymerization. β‐Lactam functionalization was achieved via reaction of the polyisoprene (PI) block with chlorosulfonyl isocyanate and subsequent reduction. The resulting block copolymers were molecularly characterized by SEC, FTIR, and NMR spectroscopies and DSC. Functionalization was found to proceed in high yields, altering the solubility properties of the PI block and those of the functionalized diblocks. Hydrogen bond formation is assumed to be responsible for the decreased crystallinity of the poly(ethylene oxide) block (PEO) in the bulk state as indicated by DSC measurements. The self‐assembly behavior of the β‐lactam functionalized poly(isoprene‐b‐ethylene oxide) copolymers (LIEO) in aqueous solutions was studied by dynamic light scattering (DLS), static light scattering (SLS), fluorescence spectroscopy, and atomic force microscopy (AFM). Nearly spherical loose aggregates were formed by the LIEO block copolymers, having lower aggregation numbers and higher cmc values compared to the IEO precursors, as a result of the increased polarity of the β‐lactam rings incorporated in the PI blocks. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 24–33, 2010     

窄分布聚丙烯酸-g-聚甲基丙烯酸酯接枝共聚物的合成

利用合成的一种新型原子转移自由基聚合大分子引发剂和从主干接枝的方法制备了窄分布的两亲性接枝共聚物聚丙烯酸-g-聚甲基丙烯酸酯, 并对其结构进行表征. 产物主链和侧链的分子量可分别通过调整单体与引发剂的投料比和反应时间进行控制, 结构规整, 侧链单体适用范围广. 该合成方法不仅推动了接枝共聚物合成研究的进展, 其产物更为两亲性接枝共聚物自组装行为的研究提供了很好的研究对象.     

Surface Structure and Stereocomplex Formation of Enantiomeric Polylactide Blends Using Poly(dimethyl siloxane) as a Probe Polymer

In the stereocomplex between enantiomeric poly(l-lactide) (l-PLA) and poly(d-lactide), crystallites formed as a result of stereocomplexation, equimolar l- and d-lactide unit sequences are packed side by side. The stereocomplex exhibits a melting temperature higher by about 50 °C than that of each homopolymer. In this study, we attempt to obtain further insight into the stereocomplex-induced surface structure of enantiomeric PLA blend films. The design of the blend systems is based on principles of surface segregation of multicomponent polymeric systems with a low surface energy, triblock copolymer (l-PLA-b-PDMS-b-l-PLA) of l-PLA and poly-(dimethyl siloxane). (l-PLA-b-PDMS-b-l-PLA/l-PLA) blend films showed the surface segregation of PDMS, regardless of blend composition while the surface composition of PDMS in the (l-PLA-b-PDMS-b-l-PLA/d-PLA) blend films was strongly depended on blend composition or a degree of complexation. These results are likely due to strong interaction between d- and l-lactide unit sequences, which prevents the surface segregation of PDMS.