Poly(trimethylene carbonate)/Poly(malic acid) Amphiphilic Diblock Copolymers as Biocompatible Nanoparticles

Amphiphilic polycarbonate–poly(hydroxyalkanoate) diblock copolymers, namely, poly(trimethylene carbonate) (PTMC)‐b‐poly(β‐malic acid) (PMLA), are reported for the first time. The synthetic strategy relies on commercially available catalysts and initiator. The controlled ring‐opening polymerization (ROP) of trimethylene carbonate (TMC) catalyzed by the organic guanidine base 1,5,7‐triazabicyclo[4.4.0]dec‐5‐ene (TBD), associated with iPrOH as an initiator, provided iPrO?PTMC?OH, which served as a macroinitiator in the controlled ROP of benzyl β‐malolactonate (MLABe) catalyzed by the neodymium triflate salt (Nd(OTf)₃). The resulting hydrophobic iPrO?PTMC‐b‐PMLABe?OH copolymers were then hydrogenolyzed into the parent iPrO?PTMC‐b‐PMLA?OH copolymers. A range of well‐defined copolymers, featuring different sizes of segments (M_n,NMR up to 9300 g mol^?1; Ð_M=1.28–1.40), were thus isolated in gram quantities, as evidenced by NMR spectroscopy, size exclusion chromatography, thermogravimetric analysis, differential scanning calorimetry, and contact angle analyses. Subsequently, PTMC‐b‐PMLA copolymers with different hydrophilic weight fractions (11–75 %) self‐assembled in phosphate‐buffered saline upon nanoprecipitation into well‐defined nano‐objects with D_h=61–176 nm, a polydispersity index <0.25, and a negative surface charge, as characterized by dynamic light scattering and zeta‐potential analyses. In addition, these nanoparticles demonstrated no significant effect on cell viability at low concentrations, and a very low cytotoxicity at high concentrations only for PTMC‐b‐PMLA copolymers exhibiting hydrophilic fractions over 47 %, thus illustrating the potential of these copolymers as promising nanoparticles.     

Poly（L—lactide）—Poly（ethylene glycol） Multiblock Copolymers：Synthesis and Properties

Poly (L-lactide)-poly (ethylene glycol) multiblock copolymers with predetermined block lengths were synthesized by polycondensation of PLA diols and PEG diacids. These copolymers presented special properties, such as better miscibility between the two components, low crystallinity and better hydrophilicity, which can be modulated by adjusting the block lengths of the two components.     

Poly(vinyl alcohol)-based Amphiphilic Copolymer Aggregates as Drug Carrying Nanoparticles

A series of amphiphilic polyisobutylene-block-poly(vinyl alcohol) (PIB-b-PVA) copolymers of constant PIB and varying PVA block length was synthesized by living carbocationic polymerization and their solution behavior was studied. The synthesis involved the preparation of polyisobutylene-b-poly(tert.-butyl vinyl ether) followed by hydrolysis with hydrogen bromide. The copolymers were characterized by gel permeation chromatography, ¹H-NMR, and MALDI-TOF MS methods. The micellization behavior of the copolymers was investigated in aqueous media by direct dissolution and dialysis using static and dynamic light scattering. The critical micelle concentration, micelle size, aggregation number, and micelle shape were determined. The ability of the aggregates as drug carrying nanodevices was also investigated by doping them with indomethacin. UV-Vis measurements showed that the solubility of indomethacine increased significantly. Our findings suggest that the solubility is largely dependent upon the block segment ratios.     

Synthesis and Characterization of Amphiphilic Poly(caprolactone) Star Block Copolymers

Summary: Novel, star‐shaped, amphiphilic block copolymers composed of fully degradable poly(caprolactone) were synthesized by sequential addition polymerization. In the first step, four‐arm macroinitiators were produced by ring‐opening polymerization of caprolactone by initiation with pentaerythritol. Then, block copolymers were synthesized by sequential addition of 4‐(2‐benzyloxyethyl)‐ε‐caprolactone to the four‐arm macroinitiators. Star‐shaped, amphiphilic block copolymers containing poly(caprolactone)‐block‐poly[4‐(2‐hydroxyethyl)caprolactone] segments were obtained by catalytic debenzylation.

Four‐arm amphiphilic polycaprolactone star block copolymer.     

Tunable Amphiphilic Poly(Ether-Anhydride) Gel Nanoparticles for the Delivery of Hydrophobic Drugs

Summary: Biodegradable amphiphilic poly(ether-anhydride) gel nanoparticles (GNPs) with a hydrophobic crosslinked core and a hydrophilic PEG shell have been prepared from amphiphilic photo-crosslinkable ether-anhydride macromers via microemulsion photo-polymerization. The properties of the GNPs, such as degradability, size and drug-loading capacity, were investigated by tailoring the length of PEG chains in macromers from 400 to 4000 and by the addition of a hydrophobic photo-crosslinkable monomer: stearic monoacrylic anhydride (MSA). TEM showed that the GNPs were spherical in shape with a core-shell structure when MSA was added. The GNPs were used as the carriers to enhance the solubility of hydrophobic drugs. Indomethacin (IND) as a model drug was entrapped in the hydrophobic crosslinked core by an in situ embedding method. Results showed that IND maintained chemically intact during the formulation process, and its dissolution rate were improved compared to those of the pure IND. The GNPs prepared from PEG macromer (molecular weight: 4000) with the addition of MSA exhibited the zero-order release behavior, which is potentially useful to control the release of hydrophobic drugs.     

Preparation of Size Tunable Amphiphilic Poly(amino acid) Nanoparticles

Size tunable amphiphilic NPs composed of poly(γ‐PGA) and hydrophobic amino acids, such as Phe or Trp, were prepared. To prepare these size‐regulated NPs, γ‐PGA‐g‐Phe or γ‐PGA‐g‐Trp dissolved in DMSO was added to various concentrations of NaCl solution. The γ‐PGA‐Phe and γ‐PGA‐Trp formed monodispersed NPs, and the size of NPs can be easily controlled by NaCl concentration. The different‐sized NPs showed the same structure. The encapsulation of protein into the different‐sized NPs was successfully achieved and the size of protein‐encapsulated γ‐PGA‐Phe NPs was increased when protein was encapsulated.

     

Synthesis and Self‐Assembly of Thermoresponsive Amphiphilic Biodegradable Polypeptide/Poly(ethyl ethylene phosphate) Block Copolymers

We report the design and synthesis of new fully biodegradable thermoresponsive amphiphilic poly(γ‐benzyl L ‐glutamate)/poly(ethyl ethylene phosphate) (PBLG‐b‐PEEP) block copolymers by ring‐opening polymerization of N‐carboxy‐γ‐benzyl L ‐glutamate anhydride (BLG? NCA) with amine‐terminated poly(ethyl ethylene phosphate) (H₂N? PEEP) as a macroinitiator. The fluorescence technique demonstrated that the block copolymers could form micelles composed of a hydrophobic core and a hydrophilic shell in aqueous solution. The morphology of the micelles as determined by transmission electron microscopy (TEM) was spherical. The size and critical micelle concentration (CMC) values of the micelles showed a decreasing trend as the PBLG segment increased. However, UV/Vis measurements showed that these block copolymers exhibited a reproducible temperature‐responsive behavior with a lower critical solution temperature (LCST) that could be tuned by the block composition and the concentration.     

Synthesis of Poly(N-ethylaniline) Nanoparticles Synthesis and Characterization of Organically Soluble Conducting Poly(N-ethylaniline) Nanoparticles using Acrylic Acid as a Soft Template

In this paper, we report the synthesis of poly(N-ethylaniline) (PNETA) by using tartaric acid (TA) as an organic acid dopant by aqueous polymerization method of N-ethylaniline using ammonium per sulphate (APS) as an oxidant and acrylic acid (AA) as a soft template. This is a new polymerization method for the direct synthesis of the emeraldine salt form of poly(N-ethylaniline) in bulk quantity, which is soluble in organic solvents such as m-cresol and N-methyl pyrrolidinone. The prepared polymers were characterized by UV, FTIR, XRD, TGA, SEM and conductivity measurement studies. The results are discussed with reference to HCl doped poly(N-ethylaniline). It is observed that PNETA/TA/AA polymer is comparatively more soluble in m-cresol than that doped with HCl in its salt form. The formation of emeraldine salt phase and dopping process was confirmed by FTIR and UV-Vis spectroscropy. We demonstrate the effect of organic dopant on the morphology and conductivity of the PNETA. It was found that, PNETA doped with TA synthesized using acrylic acid (AA) as a soft template display higher doping level, crystallinity and solubility in common organic solvent. On the contrary, HCl doped polymer was lowered at doping level and amorphous in nature which reflects the role of organic dopant and soft template. X-ray diffraction studies indicate that the PNETA/TA/AA doped samples exhibit higher crystallinity, which indicates enhanced polymer sub-chain alignment as compared to HCl doped polymer. This is also manifested by the FTIR studies. SEM result also revealed the continuous morphology and sub-micrometer size, evenly distributed particles of the PNETA/TA/AA doped polymer.     

两亲型聚L-亮氨酸-聚乙二醇单甲醚嵌段共聚物的合成与表征

开环聚合;生物降解共聚物;两亲型聚L-亮氨酸-聚乙二醇单甲醚嵌段共聚物的合成与表征     

Development of Poly(ethylene glycol) Based Amphiphilic Copolymers for Controlled Release Delivery of Carbofuran

The formation of micelles in a solvent that is selective for one of the blocks is one of the most important and useful properties of block copolymers. We had synthesized copolymers of polyethylene glycol and various dimethyl esters, which self assemble into nano micellar aggregates in aqueous media. In the present work, we have utilized these nano micelles for the encapsulation of carbofuran, [2,3–dihydro-2,2-dimethylbenzofuran-7-yl methylcarbamate], a systemic insecticide-nematicide, for the development of controlled release formulation.     

Novel Amphiphilic Block Copolymers for the Formation of Stimuli-Responsive Non-Lamellar Lipid Nanoparticles

Non-lamellar lyotropic liquid crystalline (LLC) lipid nanoparticles contain internal multidimensional nanostructures such as the inverse bicontinuous cubic and the inverse hexagonal mesophases, which can respond to external stimuli and have the potential of controlling drug release. To date, the internal LLC mesophase responsiveness of these lipid nanoparticles is largely achieved by adding ionizable small molecules to the parent lipid such as monoolein (MO), the mixture of which is then dispersed into nanoparticle suspensions by commercially available poly(ethylene oxide)–poly(propylene oxide) block copolymers. In this study, the Reversible Addition-Fragmentation chain Transfer (RAFT) technique was used to synthesize a series of novel amphiphilic block copolymers (ABCs) containing a hydrophilic poly(ethylene glycol) (PEG) block, a hydrophobic block and one or two responsive blocks, i.e., poly(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acrylate) (PTBA) and/or poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA). High throughput small angle X-ray scattering studies demonstrated that the synthesized ABCs could simultaneously stabilize a range of LLC MO nanoparticles (vesicles, cubosomes, hexosomes, inverse micelles) and provide internal particle nanostructure responsiveness to changes of hydrogen peroxide (H₂O₂) concentrations, pH and temperature. It was found that the novel functional ABCs can substitute for the commercial polymer stabilizer and the ionizable additive in the formation of next generation non-lamellar lipid nanoparticles. These novel formulations have the potential to control drug release in the tumor microenvironment with endogenous H₂O₂ and acidic pH conditions.     

（苯乙烯—丁二烯—环氧乙烷）多嵌段共聚物的合成及表征

α,ω—双羟基聚苯乙烯与α,ω—双羟基聚丁二烯及聚乙二醇为预聚体,以2,4-甲苯二异氰酸酯为偶联剂,聚合得到(苯乙烯-丁二烯-环氧乙烷)多嵌段共聚物。研究了聚合条件的影响。产物分别用热环已烷及水萃取提纯。并用IR、~1HNMR、GPC、动态粘弹谱及透射电子显微镜进行了表征。     

Phenolic Building Blocks for the Assembly of Functional Materials

Phenolic materials have long been known for their use in inks, wood coatings, and leather tanning. However, there has recently been a renewed interest in engineering advanced materials from phenolic building blocks. The intrinsic properties of phenolic compounds, such as metal chelation, hydrogen bonding, pH responsiveness, redox potentials, radical scavenging, polymerization, and light absorbance, have made them a distinct class of structural motifs for the synthesis of functional materials. Materials prepared from phenolic compounds often retain many of these useful properties with synergistic effects in applications ranging from catalysis to biomedicine. This Review provides an overview of the diverse functional materials that can be prepared from natural and synthetic phenolic building blocks, as well as their applications.     

Biotin-Conjugated Poly(Acrylic Acid)-Grafted Ultrasmall Gadolinium Oxide Nanoparticles for Enhanced Tumor Imaging

Herein, biotin (Bio)-conjugated poly(acrylic acid) (PAA)-grafted ultrasmall gadolinium oxide nanoparticles (Bio-PAA-Gd₂O₃ NPs) were synthesized for enhanced tumor imaging using Bio as a tumor-targeting ligand. The average particle diameter of Gd₂O₃ NPs was 2.1 nm. The Bio-PAA-Gd₂O₃ NPs exhibited excellent colloidal stability (i. e., no precipitation) and a high longitudinal water proton spin relaxivity (r₁) of 23.8 s⁻¹ mM⁻¹ (r₂/r₁=1.6 and r₂=transverse water proton spin relaxivity), which was ∼6 times higher than those of commercial Gd-chelated magnetic resonance imaging (MRI) contrast agents. Cytotoxicity tests using two cell lines showed that the Bio-PAA-Gd₂O₃ NPs were almost non-toxic up to the measured concentration of 500 μM Gd. The enhanced tumor imaging of the Bio-PAA-Gd₂O₃ NPs was demonstrated through their higher positive contrasts and longer contrast retention at the tumor after intravenous injection in T₁ MR images, compared with those of the control PAA-Gd₂O₃ NPs.     

Functional Amphiphilic Poly(2-oxazoline) Block Copolymers as Drug Carriers: the Relationship between Structure and Drug Loading Capacity

Poly(2-oxazoline)(POx) is a kind of polymeric amides that can be viewed as conformational isomers of polypeptides with excellent cyto-and hemo-compatibility, and is promising to be used as drug carriers. However, the drug loading capacity(DLC) of POx for many drugs is still low except several hydrophobic ones including paclitaxel(PTX). Herein, we prepared a series of amphiphilic POx block copolymers with various functional groups, and investigated the relationship between functional structures a...     

聚(Nε-苄氧羰基赖氨酸)-聚乙二醇-聚(Nε-苄氧羰基赖氨酸)的合成及其表征

利用三光气合成了Nε-苄氧羰基赖氨酸酸酐(Lys(z)-NCA),并用双端氨基聚乙二醇做引发剂,在DMF中引发Lys(z)-NCA聚合,合成了聚(Nε-苄氧羰基赖氨酸)-聚乙二醇-聚(Nε-苄氧羰基赖氨酸)三嵌段共聚物.利用IR、1H NMR、DSC和GPC对其结构进行了表征,结果表明,这种方法能够合成分子量可控、分子量分布窄(Ip=1.06)的嵌段共聚物,产率95.4%.     

Resorcinarene-Encapsulated Nanoparticles: Building Blocks for Self-Assembled Nanostructures

Calix[4]resorcinarene-derived surfactants are highly effectiveat stabilizing metal nanoparticles of different sizes, creating opportunities tofabricate well-defined nanostructures with size-tunable materials properties. Theresorcinarenes have a critical role in the dispersion of nanoparticles under varioussolvent conditions and in the robustness of the protective surfactant layer.Magnetic cobalt particles stabilized by resorcinarenes self-assemble intonanostructured ``bracelets' in toluene. Resorcinarene surfactants can also promote theself-organization of gold nanoparticles as large as 170 nm into two-dimensional arrays. Thesenanostructured films possess novel optoelectronic properties such as surface-enhancedRaman scattering (SERS), and are expected to have useful applications for chemical sensing.     

Multiblock Copolymers Based on Highly Crystalline Polyethylene and Soft Poly(ethylene-co-butadiene) Segments: Towards Polyolefin Thermoplastic Elastomers

Block copolymers based on polyethylene (PE) and ethylene butadiene rubber (EBR) were obtained by successive controlled coordinative chain transfer polymerization (CCTP) of a mixture of ethylene and butadiene (80/20) and pure ethylene. EBR-b-PE diblock copolymers were synthesized using the {Me₂Si(C₁₃H₈)₂Nd(BH₄)₂Li(THF)}₂ complex in combination with n-butyl,n-octyl magnesium (BOMAG) used as both the alkylating and chain transfer agent (CTA). Triblock and multiblock copolymers featuring highly semi-crystalline PE hard segments and soft EBR segments were further obtained by the development of a bimetallic CTA, the pentanediyl-1,5-di(magnesium bromide) (PDMB). These new block copolymers undergo crystallization-driven organization into lamellar structures and exhibit a variety of mechanical properties, including excellent extensibility and elastic recovery in the case of triblock and multiblock copolymers.