Aggregation phenomena of linear and miktoarm star copolymers of styrene and dimethylsiloxane: Influence of the architecture

The micellar behavior of PS-b-PDMS, PS-b-PDMS-b-PS linear block and (PS)₂(PDMS) miktoarm star copolymers of polystyrene (PS) and polydimethylsiloxane (PDMS) is investigated in DMF, a selective solvent for PS. The linear PS-b-PDMS and star (PS)₂(PDMS) copolymers exhibit different macromolecular architectures but similar compositions and total molecular weight, while the linear PS-b-PDMS-b-PS copolymer has the same composition as the diblock and miktoarm star but double their molecular weight. Static, dynamic light scattering and viscometry were used for the structural characterization of the micelles. Aggregation numbers were found to increase in the order PS-b-PDMS-b-PS < (PS)₂(PDMS) < PS-b-PDMS. The corona thickness was dependent on the molecular weight of the soluble PS chains. In the case of (PS)₂(PDMS), although the core area per PS chain, A_C, was significantly lower than that of the linear copolymers, the coronal chains were not significantly stretched. This can be attributed to the stiff nature of the PS chains, which maintains the elongated form of the chains.     

Super-nucleation in nanocomposites and confinement effects on the crystallizable components within block copolymers, miktoarm star copolymers and nanocomposites

In this paper we reexamine recent results obtained by our group on the crystallization of nanocomposites and linear and miktoarm star copolymers in order to obtain some general features of their crystallization properties. Different nanocomposites have been prepared where a close interaction between the polymer matrix and the nano-filler has been achieved: in situ polymerized high density polyethylene (HDPE) on carbon nanotubes (CNT); and polycaprolactone (PCL) and poly(ethylene oxide) (PEO) covalently bonded to carbon nanotubes. In all these nanocomposites a “super-nucleation” effect was detected where the CNTs perform a more efficient nucleating action than the self-nuclei of the polymer matrix. It is believed that such a super-nucleation effect stems from the fact that the polymer chains are tethered to the surface of the CNT and can easily form nuclei. For polystyrene (PS) and PCL block copolymers, miktoarm star copolymers (with two arms of PS and two arms of PCL) were found to display more compact morphologies for equivalent compositions than linear PS-b-PCL diblock copolymers. As a consequence, the crystallization of the PCL component always experienced much higher confinement in the miktoarm stars case than in the linear diblock copolymer case. The consequences of the topological confinement of the chains in block copolymers and nanocomposites on the crystallization were the same even though the origin of the effect is different in each case. For nanocomposites a competition between super-nucleation and confinement was detected and the behavior was dominated by one or the other depending on the nano-filler content. At low contents the super-nucleation effect dominates. In both cases, the confinement increases as the nano-filler content increases or the second block content increases (in this case a non-crystallizable block such as PS). The consequences of confinement are: a reduction of both crystallization and melting temperatures, a strong reduction of the crystallinity degree, an increase in the supercooling needed for isothermal crystallization, a depression of the overall crystallization rate and a decrease in the Avrami index until values of one or lower are achieved indicating a nucleation control on the overall crystallization kinetics.     

Synthesis of ABCD‐type miktoarm star copolymers and transformation into zwitterionic star copolymers

ABCD‐type 4‐miktoarm star copolymers of styrene (St), α‐methylstyrene (αMSt), tert‐butyl methacrylate (tBuMA), and 4‐vinylpyridine (4VP) were synthesized via anionic polymerization using 1,3‐bis(1‐phenylvinyl)benzene (m‐DDPE) as the linking molecule. The synthetic route was rationally designed with respect to the reactivity of individual propagating anion towards the double bond of m‐DDPE. Thus the synthesis includes several consecutive key reactions, for example, the monoaddition of polystyryllithium towards m‐DDPE, the polymerization of tBuMA initiated by the resulting monoadduct to produce a diblock macromonomer, the coupling of the macromonomer with poly(α‐methylstyryl)lithium to form a 3‐arm star anion, and the polymerization of 4‐vinylpyridine initiated by the star anion. These reactions were conducted either in a one‐pot process, in which the diblock macromonomer was in situ coupled with poly(α‐methylstyryl)lithium, or in a batch polymerization process, in which the same diblock macromonomer was separated. The final product was hydrolyzed to produce a zwitterionic miktoarm star copolymer, which was soluble at lower pH but insoluble in neutral and basic solution. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 4818–4828, 2007     

Synthesis of miktoarm star (block) polymers based on a heterofunctional initiator via combination of ROP, ATRP and functional group transformation

Versatile miktoarm three-arm star polymers, (polystyrene)(polyε-caprolactone)₂ ((PS)(PCL)₂), (PS-b-poly(n-butyl acrylate))(PCL-b-PS-b-poly(n-butyl acrylate))₂ ((PS-b-PnBA)(PCL-b-PS-b-PnBA)₂) and (PtBA-b-PS)(PCL-b-PtBA-b-PS)₂ were synthesized via combination of atom-transfer radical polymerization (ATRP), functional group transformation technique and ring opening polymerization (ROP) using 1,1-dihydroxymethyl-1-(2-bromoisobutyryloxy)methyl ethane (DHB) as a heterofunctional initiator. In the synthesis of (PS)(PCL)₂ by combination of ROP of ε-caprolactone (ε-CL) and ATRP, the implementation sequence, ROP followed by ATRP, was proved to be effective to get a well-defined miktoarm star polymer than the reverse one. The two miktoarm star block polymers, (PS-b-PnBA)(PCL-b-PS-b-PnBA)₂ and (PtBA-b-PS)(PCL-b-PtBA-b-PS)₂, were prepared by one ROP step, one group transformation and ATRP steps using the same initiator. All the polymers have defined structures and their molecular weights are adjustable with good controllability.     

Synthesis and characterization of miktoarm star copolymer of styrene and butadiene using multifunctional macromolecular initiator

A new kind of multifunctional macromolecular initiator with Sn-C bonds and polydiene arms was synthesized by living anionic polymerization.At first,polydiene-stannum chloride(PD-SnCl_3) was prepared by the reaction of n-butyl-Li(n-BuLi),stannic chloride(SnCl_4) and diene.Then PD-SnCl_3 was used to react with the dilithium initiator to prepare the multifunctional organic macromolecular initiators.The result suggested that the initiators had a remarkable yield by GPC,nearly 90%.By using these multifunction...     

Fluorescent micelles based on star amphiphilic copolymer with a porphyrin core for bioimaging and drug delivery

Star-shaped poly(ε-caprolactone)-b-poly(ethylene oxide) amphiphilic copolymer with a tetrakis-(4-aminophenyl)-terminated porphyrin core was synthesized. Paclitaxel (PTX)-loaded polymeric micelles were prepared by the self-assembly of the star copolymer and in situ encapsulation of PTX. The fluorescent characteristic of the porphyrin moiety allowed the cellular uptake and biodistribution of the PTX-loaded micelles to be monitored by fluorescent imaging. The PTX-loaded micelles can be readily internalized by cancer cells and have a slightly higher cytotoxicity than clinic PTX injection Taxol. In vivo real-time fluorescent imaging revealed that the micelles could accumulate at tumor site via the blood circulation in tumor-bearing mice. In vivo antitumor efficacy examinations indicated that the PTX-loaded micelles had significantly superior efficacy in impeding tumor growth than Taxol and low toxicity to the living mice.     

Amphiphilic well-defined degradable star block copolymers by combination of ring-opening polymerization and atom transfer radical polymerization: Synthesis and application as drug delivery carriers

Atom transfer radical polymerization (ATRP) is one of the most popular advanced polymerization techniques in macromolecular science, allowing the synthesis of tailor-made polymers with controlled molecular weight, architecture, composition, and functionality. The combination of ATRP and ring-opening polymerization (ROP) provides a straightforward route for the preparation of polymers exhibiting both targeted and well-defined features and biodegradability, which is very interesting for the development of new materials for biomedical applications. Among the different types of polymer architectures, amphiphilic star block copolymers (BCPs) represent a very attractive one, due to their high degree of functionality at the molecular surface, low hydrodynamic volume and higher encapsulation ability, compared to molecular systems based on linear polymers. This review article highlights the research focused on the synthesis of amphiphilic well-defined degradable star BCPs by combination of ROP and ATRP, with particular focus on the development of polymers for biomedical applications, such as anticancer drug delivery, diagnosis therapy, or photodynamic therapy, which is the most investigated field regarding these polymers.     

The role of crown ethers in drug delivery

The unique structure of the crown ethers has attracted the attention of many scientists to the use of these compounds in organic synthesis, and drug delivery. In recent years, extensive research has been conducted on the use of crown ethers in the drug delivery process. In the drug delivery process, the use of compounds that can act selectively is very important. Crown ethers with their unique structure can appear in various roles in drug delivery. In recent years, the use of crown ethers in the formulation of nano-drugs have attracted the attention of many researchers, and it shows that crown ethers have a great potential in the process of drug delivery. In fact, chemistry plays a role as a medium for transferring information from suitable compounds to drug delivery. Reviewing the results of the research provides the opportunity to create new ideas for using crown ether in new drug delivery systems.     

肽类树枝状大分子:自组装胶束及药物释放研究

本文以三代聚谷氨酸肽类树枝状分子(G3-Glu)为大分子引发剂,引发N-羧基-L-苯丙氨酸-环内酸酐(NCA-Phe)的开环聚合反应,制备聚谷氨酸树枝状大分子-聚苯丙氨酸嵌段共聚物.嵌段共聚物通过自组装形成以聚苯丙氨酸链段为核,聚谷氨酸树枝状大分子为壳的胶束.将抗肿瘤药物阿霉素负载到高分子胶束中,研究其药物释放性能及体外抗肿瘤效果.结果表明,共聚物胶束具有良好的生物相容性.载药胶束具有药物缓释效果,药物持续释放时间可达60h.载药胶束的体外抗肿瘤实验表明其对肝癌细胞HepG2具有很好的杀灭效果,共培养48h后对癌细胞的杀死率可高达75%.     

Polypeptide dendrimers: Self-assembly and drug delivery

Amphiphilic dendritic poly(glutamic acid)-b-polyphenylalanine copolymers were synthesized using generation 3 dendritic poly(glutamic acid) as the macroinitiator in the ring-opening polymerization of NCA-Phe.The block copolymers self-assembled micelles with polyphenylalanine segments as core and dendritic poly(glutamic acid) segments as shell.The biocompatibility of the micelles was studied.The release of the anticancer drug doxorubicin from the micelles was investigated in vitro.The results showed that the ...     

Hydrodynamic properties of model 3-miktoarm star copolymers

The synthesis of well-defined, nearly monodispersed, 3-miktoarm (from the greek word μlkτós meaning mixed) star copolymer of the A₂B type is described. A and B is either polystyrene (PS), polybutadiene (PBd), or polyisoprene (PI). The sequential controlled addition of living anionic B and A chains to methyltrichlorosilane leads to narrow molecular weight distribution miktoarm star copolymers with homogeneous composition. Characterization was carried out by size exclusion chromatography, low-angle laser light scattering, laser differential refractometry, membrane and vapor pressure osmometry, nuclear magnetic resonance and ultraviolet spectroscopy. Analysis of [η], R_H and R_v of the A₂B and one A₂B₂ miktoarm copolymers, suggests that a small expansion of the copolymer occurs either in a good solvent for both species or in a Θ solvent for one of them, as compared with the corresponding star homopolymers. This is in contrast to results obtained on linear block copolymers, and is due to the increased occurrence of heterocontacts in the miktoarm starshaped architecture. © 1995 John Wiley & Sons, Inc.     

Synthesis of ABC-type miktoarm star polymers by “click” chemistry, ATRP and ROP

ABC-type miktoarm star polymers, poly(ethylene oxide)-block-polystyrene-block-poly (ε-caprolactone)s (PEO-b-PS-b-PCL) were synthesized via combination of “click” chemistry, atom-transfer radical polymerization (ATRP) and ring opening polymerization (ROP). Azide ended PEO arms, PEO-N₃, and a trifunctional molecule, propargyl 2-hydroxylmethyl-2-(α-bromoisobutyraloxymethyl)-propionate (PHBP), were prepared first, respectively. A “click” reaction of PEO-N₃ and PHBP generated a PEO macroinitiator, PEO-(Br)(OH) with two functionalities, one is hydroxyl group and the other is α-bromoisobutyraloxyl group. Consecutive ATRP of styrene (St) and ROP of ε-caprolactone (ε-CL) from the PEO macroinitiator produced the PEO-b-PS-b-PCL miktoarm stars. All the structures of the polymers were determined.     

星形聚氧乙烯及星形杂臂氧化乙烯-苯乙烯共聚物的合成

以原子转移自由基偶联法合成了多臂星形聚合物S-PEO和星形杂臂共聚物PEO-PS。以傅立叶红外光谱(FT-IR)和核磁共振(1H NMR)分析方法确定了产物的结构。以GPC分析测试了产物的分子量和分子量分布。GPC分析结果表明所得聚合物分子量增大,分子量分布窄,偶联反应效率可高达99%以上。     

Synthesis of miktoarm star and miktoarm star block copolymers via a combination of atom transfer radical polymerization and stable free‐radical polymerization

A trifunctional initiator, 2‐phenyl‐2‐[(2,2,6,6‐tetramethyl)‐1‐piperidinyloxy] ethyl 2,2‐bis[methyl(2‐bromopropionato)] propionate, was synthesized and used for the synthesis of miktoarm star AB₂ and miktoarm star block AB₂C₂ copolymers via a combination of stable free‐radical polymerization (SFRP) and atom transfer radical polymerization (ATRP) in a two‐step or three‐step reaction sequence, respectively. In the first step, a polystyrene (PSt) macroinitiator with dual ω‐bromo functionality was obtained by SFRP of styrene (St) in bulk at 125 °C. Next, this PSt precursor was used as a macroinitiator for ATRP of tert‐butyl acrylate (tBA) in the presence of Cu(I)Br and pentamethyldiethylenetriamine at 80 °C, affording miktoarm star (PSt)(PtBA)₂ [where PtBA is poly(tert‐butyl acrylate)]. In the third step, the obtained St(tBA)₂ macroinitiator with two terminal bromine groups was further polymerized with methyl methacrylate by ATRP, and this resulted in (PSt)(PtBA)₂(PMMA)₂‐type miktoarm star block copolymer [where PMMA is poly(methyl methacrylate)] with a controlled molecular weight and a moderate polydispersity (weight‐average molecular weight/number‐average molecular weight < 1.38). All polymers were characterized by gel permeation chromatography and ¹H NMR. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 2542–2548, 2003     

Block and star block copolymers by mechanism transformation X. Synthesis of poly(ethylene oxide) methyl ether/polystyrene/poly(l-lactide) ABC miktoarm star copolymers by combination of RAFT and ROP

Poly(ethylene oxide) methyl ether/polystyrene/poly(l-lactide) (MPEO/PSt/PLLA) ABC miktoarm star copolymers were synthesized by combination of reversible addition-fragmentation transfer (RAFT) polymerization and ring-opening polymerization (ROP) using bifunctional macro-transfer agent, MPEO with two terminal dithiobenzoate and hydroxyl groups. It was prepared by reaction of MPEO with maleic anhydride (MAh), subsequently reacted with dithiobenzoic acid and ethylene oxide. RAFT polymerization of St at 110 °C yielded block copolymer, MPEO-b-PSt [(MPEO)(PSt)CH₂OH], and then it was used to initiate the polymerization of l-lactide in the presence of Sn(OCt)₂ at 115 °C to produce ABC miktoarm star polymers, s-[(MPEO)(PSt)(PLLA)]. The structures of products obtained at each synthetic step were confirmed by NMR and gel permeation chromatography data.     

A2B2 type miktoarm star copolymers via alkyne homocoupling reaction

The terminal alkyne homocoupling reaction (oxidative alkyne coupling) is presented here as a new route for the preparation of A₂B₂ type 4‐miktoarm star copolymer. The block copolymer with terminal alkyne at the junction point prepared by NMP‐ATRP and ROP‐NMP sequential routes is coupled via diyne formation to give (PS)₂‐(PMMA)₂ and (PCL)₂‐(PS)₂ 4‐miktoarm star polymers, respectively, by using a combination of (PPh₃)₂PdCl₂/PPh₃/CuI in a solvent mixture of Et₃N/CH₃CN at room temperature for 72 h. The molecular weight, intrinsic viscosity ([η]), radius of gyration (R_g), and hydrodynamic radius (R_h) of A₂B₂ 4‐miktoarm star copolymers were calculated using triple‐detection GPC as results of three detectors response. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 6703–6711, 2008     

Supramolecular self-assembly and controllable drug release of thermosensitive hyperbranched multiarm copolymers

A novel temperature-responsive hyperbranched multiarm copolymer with a hydrophobic hyperbranched poly(3-ethyl-3-(hydroxymethyl)oxetane)(HBPO) core and thermosensitive poly(N-isopropylacrylamide)(PNIPAM) arms was synthesized via the atom transfer radical polymerization(ATRP) of NIPAM monomers from a hyperbranched HBPO macroinitiator.It was found that HBPO-star-PNIPAM self-assembled into multimolecular micelles(around 60 nm) in water at room temperature according to pyrene probe fluorescence spectrometry,1H N...     

Two sides to supramolecular drug delivery systems

Although still in its infancy, there is a rapidly increasing interest in the development of supramolecular drug delivery systems (SDDSs). As chemists, the most challenging task ahead of us is to narrow the gap between SDDSs development in the lab, and clinical drug carriers. Only then will we achieve our ultimate goal of the successful translation of SDDSs to life saving medicines.     

Biocompatible amphiphilic conetwork based on crosslinked star copolymers: A potential drug carrier

A series of amphiphilic conetworks (APCNs) is synthesized through crosslinking of well‐defined tri‐arm star diblock copolymers via atom transfer radical polymerization. A new three‐arm initiator is synthesized to initiate the polymerization of 2‐hydroxyethyl methacrylate (HEMA) via “core‐first” method. The resulting star HEMA homopolymers with well‐defined molecular weight and narrow polydispersity are used as macroinitiator to incorporate allyl methacrylate to get the star diblock copolymers. Then, the precursors with allyl pendant groups are fully crosslinked with polyhydrosiloxanes through hydrosilylation. The so‐prepared APCNs exhibit unique properties of microphase separation of hydrophilic (HI) and hydrophobic (HO) phases with small channel size, a variable swelling capacity, excellent biocompatibility, and outstanding mechanical strength (2 ± 0.5 MPa). The properties of APCNs depend on the ratio of HI to HO, which can be regulated via precise synthesis of the star diblock copolymers. The APCNs show well‐controlled drug release to choline theophyllinate, suggesting a promising intelligent drug carrier for controlled release. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 2537–2545     

Micelle or polymersome formation by PCL-PEG-PCL copolymers as drug delivery systems

Polymeric micelles and polymersomes may have great potential as the drug delivery vehicles for solubilization of hydrophobic drugs.