Hybrid alginate beads with thermal‐responsive gates for smart drug delivery

Polysaccharide‐based thermo‐responsive material was prepared by grafting PNIPAAm onto hybrid alginate beads, in which a biomineralized polyelectrolyte layer was constructed aiming to enhance the mechanical strength and ensure higher graft efficiency. XPS results demonstrated that the incorporation of PNIPAAm to the hybrid beads was successful, and the PNIPAAm‐grafted beads were more hydrophilic than the ungrafted ones as indicated by their swelling behavior. The drug release behaviors revealed that the grafted beads were both thermo‐ and pH‐sensitive, and the PNIPAAm existed in the pores of the alginate beads acted as the “on–off” gates: the pores of the beads were covered by the stretched PNIPAAm to delay the drug release at 25°C and opened to accelerate the drug release at 37°C because of the shrinking of PNIPAAm molecules. This paper would be a useful example of grafting thermo‐responsive polymers onto biodegradable natural polymer substrate. The obtained beads provide a new mode of behavior for thermo‐responsive “smart” polysaccharide materials, which is highly attractive for targeting drug delivery system and chemical separation. Copyright © 2010 John Wiley & Sons, Ltd.     

Synthesis of a biodegradable polymeric supramolecular assembly for drug delivery

A novel design of a biodegradable carrier for drug delivery was established by constructing a supramolecular assembly of drugs and polymer backbones without any covalent bonds. A biodegradable polyrotaxane was synthesized in which α-cyclodextrins (α-CDs) as drug carriers were threaded onto poly(ethylene glycol) chains which then were capped at each chain end by L -phenylalanine via peptide linkages. The release of α-CDs was observed only when the terminal peptide linkages were degraded.     

Use of quasi-SMILES to model biological activity of “micelle–polymer” samples

The basic task of the drug discovery is the establishing of molecular structure of new pharmaceutical agents. To define the molecular structure is only half of the way to new drug. The transport of active molecules to appropriate targets in an organism should be elucidated in details. The selection of polymeric structures playing the role of basis for transport of therapeutic agents into the body is one of the ways to solve the task. Drug loading capacity (DLC) and critical micelle concentration (CMC) are measures of ability of “polymer–micelle” systems to be suitable for the process of the transport of therapeutic agents into an organism. Polymeric micelles are a type of complex multi-phase and multicomponent chemical process and can be used to transport drug into an organism. Prediction of ability of “micelle–polymer” systems to be a tool for transport of therapeutic agents to targets in organism is an important task. Models, which are a mathematical function of available eclectic information about architecture of micelles and polymers, are suggested. The eclectic data are represented via the so-called quasi-simplified molecular input-line entry system (SMILES), which are analogy of traditional SMILES. The quasi-SMILES contain some additional information besides the molecular architecture (physicochemical and biochemical conditions). Predictive potential of these models is good.

     

Ag Nanocomposite Particles: Preparation,Characterization and Application

Summary Herein, we report that different core-shell particles could be successfully used as the carrier systems for the deposition of silver nanoparticles. Firstly, thermosensitive core-shell microgel particles have been used as the carrier system for the deposition of Ag nanoparticles, in which the core consists of poly (styrene) (PS) whereas the shell consists of poly (N-isopropylacrylamide) (PNIPA) network cross-linked by N, N′-methylenebisacrylamide (BIS). Immersed in water the shell of these particles is swollen. Heating the suspension above 32 °C leads to a volume transition within the shell, which is followed by a marked shrinking of the network of the shell. Secondly, “nano-tree” type polymer brush can be used as “nanoreactor” for the generation of silver nanoparticles also. This kind of carrier particles consists of a solid core of PS onto which bottlebrush chains synthesized by the macromonomer poly (ethylene glycol) methacrylate (PEGMA) are affixed by “grafting from” technique. Thirdly, silver nanoparticles can be in-situ immobilized onto polystyrene (PS) core-polyacrylic acid (PAA) polyelectrolyte brush particles by UV irradiation. Monodisperse Ag nanoparticles with diameter of 8.5 nm, 7.5 nm and 3 nm can be deposited into thermosensitive microgels, “nano-tree” type polymer brushes and polyelectrolyte brush particles, respectively. Moreover, obtained silver nano-composites show different catalytic activity for the catalytic reduction of p-nitrophenol depending on the carrier system used for preparation.     

Dendron–polymer conjugates via the diels–alder “click” reaction of novel anthracene‐based dendrons

Diblock and triblock dendron–polymer conjugates containing biodegradable polyester dendron blocks and polyethylene glycol (PEG) polymer were synthesized using the Diels–Alder “click” cycloaddition reaction. PEG polymers with furan‐protected maleimide functionality were synthesized and reacted with biodegradable polyester dendrons containing an anthracene moiety at their focal point. First through third generations of biodegradable polyester dendrons containing an anthracene unit at their focal point were synthesized using a divergent strategy. Efficient conjugation of the dendrons to polymers was demonstrated using ¹HNMR and size exclusion chromatography. This modular approach provides an easy access to the design of multivalent PEG conjugates. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3191–3201     

Groups of Organic Molecules That Operate Collectively

A “chemical system” is defined as an assemblage of molecules that collectively does something interesting or useful. The key word here is “collectively”, a word that implies an interdependency and a group behavior that can be quite different from that of individual molecules. Batteries, computer chips, concrete, mayonnaise, shampoo, paint, liquid crystal displays, composites, and viruses are all examples of commonly encountered systems. A host–guest or “supramolecular” complex, on the other hand, would not be considered a system (as defined here), because only two species are involved. A chemical system is multimolecular, a collection of molecules interlocked in a tangle of dependencies. The review delves into a variety of chemical systems investigated by the author, including micelles, water pools, films, vesicles, and polymers. All of them can be categorized as “self-assembling” or “self-organizing” in the sense that defined structures arise spontaneously owing to noncovalent forces among the component molecules. Such chemical systems are useful for many purposes, including decontamination of environmentally dangerous substances, drug delivery, and separation of organic compounds.     

Characteristics of a single‐layered organic electroluminescent device using a carrier‐transporting copolymer and a nonconjugated light‐emitting polymer

We have synthesized a novel carrier‐transporting copolymer and a nonconjugated light‐emitting polymer. The carrier‐transporting copolymer has a triphenylamine moiety as a hole‐transporting unit and a triazine moiety as an electron‐transporting unit, both of which are located in the polymer side chain. The nonconjugated light‐emitting polymer has a perylene moiety, which acts as an emitting unit in the polymer side chain. These polymers are very soluble in most organic solvents, such as monochlorobenzene, tetrahydrofuran, chloroform, and benzene. A single‐layered electroluminescent device consisting of ITO/copolymer and emitting‐material 4‐(dicyanomethylene)‐2‐methyl‐6‐(4‐dimethylaminostyryl)‐4H‐pyran (DCM) or light‐emitting polymer)/Al mixtures exhibits maximum external quantum efficiency when the concentration of the emitting material is 30 wt %. The device emits red or blue light according to the emitting material. When CsF is used as the electron‐injecting material, the drive voltage decreases drastically to 7 V, and the highest quantum efficiency is 0.5%. © 2003 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 41: 2733–2743, 2003     

On conformation of molecules of aromatic polyamides in solutions

On the basis of experimental data concerning the equilibrium rigidity of molecules of aromatic polyamides, possible structures of molecules of poly-?-benzamide (PPBA) and other aromatic polyamides with phenyl rings included in the chain in the para position have been considered.It is shown that extremely high equilibrium rigidity of these polymer molecules is due to the coplanar trans-structure of their amide groups leading to a “crankshaft”-like conformation of the chain.The equilibrium rigidity of the chain estimated with the aid of this model is in good agreement with experimental data.It is shown that the main factors determining the equilibrium flexibility of the PPBA molecules are the inequality of valence angles at carbon and nitrogen atoms of the amide group and also a departure from coplanarity of the amide group due to thermal motion of the chain.     

Strongly stretched polymer brushes

Polymer “brushes” are formed when long-chain molecules are somehow attached by one end at an interface with a relatively small area per chain. Such adsorbed brushes in the presence of solvent may be used to modify surface properties, stabilize colloidal particles, etc. Strongly segregated block copolymer phases, or interfacial layers of such “polymeric surfactants” may also be modeled in terms of “melt brushes,” (i.e., brushes without solvent). In both cases, when chain attachments are crowded on the interface, the chains stretch out to avoid neighboring chains. The resulting physical state has properties markedly different from polymer solutions, gels, or weakly adsorbed polymer layers. When the chains are strongly stretched, their statistical mechanics become simpler, as fluctuations around the set of most probable conformations are suppressed. This makes possible many pencil-and-paper calculations of brush properties, including bending and compressional moduli, and detailed knowledge of the chain conformations. As a recent example, I will describe calculations of phase diagrams of strongly segregated block copolymers including bicontinuous double-diamond phases. © 1994 John Wiley & Sons, Inc.     

Biodegradable Micelles Capable of Mannose‐Mediated Targeted Drug Delivery to Cancer Cells

A targeted micellar drug delivery system is developed from a biocompatible and biodegradable amphiphilic polyester, poly(Lac‐OCA)‐b‐(poly(Tyr(alkynyl)‐OCA)‐g‐mannose) (PLA‐b‐(PTA‐g‐mannose), that is synthesized via controlled ring‐opening polymerization of O‐carboxyanhydride (OCA) and highly efficient “Click” chemistry. Doxorubicin (DOX), a model lipophilic anticancer drug, can be effectively encapsulated into the micelles, and the mannose moiety allows active targeting of the micelles to cancer cells that specifically express mannose receptors, which thereafter enhances the anticancer efficiency of the drug. Comprised entirely of biodegradable and biocompatible polyesters, this micellar system demonstrates promising potentials for targeted drug delivery and cancer therapy.

     

New polymer systems exhibiting microphase separation transition with the formation of nano-microstructures

The concept of microphase separation was up to now widely applied mainly to the conformational transitions in block-copolymer solutions and melts. However, recently it became obvious that this concept has a much more general meaning. It was shown that microphase separation transition can be observed in random copolymers, interpenetrating polymer networks, polyelectrolyte mixtures, poor solvent polyelectrolyte solutions, ionomer solutions and melts, polymer blends and solutions with nonlocal entropy of mixing. In all these examples the emerging microdomain structures correspond to the nanometer scale, therefore the study of these effects can lead to the new ways of obtaining polymer materials with controlled nano-microstructure. In this presentation the review of our recent findings on microphase separation in some of the above-mentioned systems will be presented. 1. The problem of microphase separation in the systems containing weakly charged polyelectrolytes (polyelectrolyte mixtures and poor solvent polyelectrolyte solutions) will be considered. From the methodic point of view, it will be shown that this problem can be solved by direct minimization of the free energy, without the use of “weak segregation” or “strong segregation” assumptions which are common in the theory of block-copolymers. The final phase diagrams exhibit wide macroscopic phase separation regions, which is their main difference from the corresponding phase diagrams for block-copolymer systems. The formation of microdomains is thus coupled with macroscopic phase separation: in most of the cases microdomain structure is formed in one of the coexisting phases after macroscopic phase separation takes place [1] - [2]. 2. The formation of the multiplet structure in ionomer melts and solutions can be also considered as the microphase separation in the random copolymer system with the formation of the “micelles” (or clusters) of ionic links. The parallels with micelle formation in block-copolymer systems can be established if one considers a new “superstrong segregation regime” for block-copolymer microstructures. This regime can be indeed observed for diblock copolymers with one ionomeric and one neutral block [3]. 3. The microphase separation transition in ordinary polymer blends and solutions is also possible. The conditions for this effect are: (i) significant entropic contribution to polymer/polymer or polymer/solvent miscibility, (ii) the nonlocal character of this contribution with a high value of the nonlocality radius. It is argued that one can expect that the entropy nonlocality radius increases in the vicinity of the glass transition for the blend or polymer solutions (in the latter case solvent molecules act like “poor solvent plasticisers”). Computer simulation data supporting the theoretical prediction of microphase separation transition in these systems will be presented [4] - [5].     

Carrier gas UV laser ablation sensitizers for photopolymerized thin films

Designed carrier gas UV laser ablation sensitizers were synthesized and proved to greatly enhance the UV laser ablation of photopolymerized thin films. Polymers containing dense ester groups are reported to have better laser ablation performance because of the tendency of the ester groups to decompose into gaseous products (“carrier gases”) during the ablation process. In order to introduce this mechanism to cationic UV curable coatings for better laser ablation, a series of “carrier gas” sensitizers were synthesized by reacting hydroxyl containing reactive diluents such as oxetane and polyester polyols with monomethyl oxalyl chloride or dimethyl oxalate; the oxalyl group is considered a “carrier gas” generating moiety. Furthermore, a UV absorbing chromophore, naphthalene, is either chemically bound to the oxalyl containing molecules or blended with the synthesized oxalyl containing compounds to produce a synergistic effect. The “carrier gas” sensitizers were added into a typical cationic UV curable formulation to form sensitized coatings, which were then characterized by thermogravimetric analysis, real time FTIR and ablated by a 355 nm laser. The ablation vias were examined using optical profilometry and SEM. Compared to the control, the sensitized coatings were found to have similar thermal decomposition temperatures and higher functional group conversion during photopolymerization. All of the sensitized coatings containing the “carrier gas” sensitizers exhibited better UV laser ablation performance than the control. The combination of naphthalene derivatives and the oxalyl group gave a better ablation result, suggesting a synergistic effect. The chemical combination of the naphthalene and oxalyl group exhibited better ablation sensitization than their blends, suggesting a more efficient intramolecular laser energy utilization process.     

Lipid carrier systems for targeted drug and gene delivery

For effective chemotherapy, it is necessary to deliver therapeutic agents selectively to their target sites, since most drugs are associated with both beneficial effects and side effects. The use of lipid dispersion carrier systems, such as lipid emulsions and liposomes, as carriers of lipophilic drugs has attracted particular interest. A drug delivery system can be defined as a methodology for manipulating drug distribution in the body. Since drug distribution depends on the carrier, administration route, particle size of the carrier, lipid composition of the carrier, electric charge of the carrier and ligand density of the targeting carrier, these factors must be optimized. Recently, the lipid carrier system has also been applied to gene delivery systems for gene therapy. However, in both drug and gene medicine cases, a lack of cell-selectivity limits the wide application of this kind of drug and/or gene therapy. Therefore, lipid carrier systems for targeted drug and gene delivery must be developed for the rational therapy. In this review, we shall focus on the progress of research into lipid carrier systems for drug and gene delivery following systemic or local injection.     

功能多肽在肿瘤治疗中的应用及研究进展

多肽具有生物相容性好,功能多样化,生物体内响应性高及合成修饰方法简单易行等优点,已被广泛用于构建靶向药物传递系统。以具有靶向功能和刺激响应性的多肽为基础构建的药物传递系统,能够将药物定向地运送到肿瘤区域。药物传递系统到达肿瘤组织后,在肿瘤组织特殊微环境或外源刺激下,实现药物的精准释放。这种具有特异性肿瘤靶向和刺激响应型的多肽载体可以最大程度地提高药物的抗肿瘤效果,降低药物的毒副作用。本文简要介绍了常用的靶向多肽和刺激响应型多肽,并讨论了基于功能型多肽的药物载体在肿瘤治疗方面的应用。     

“Supramolecular” Amphiphiles Created by Wrapping Poly(styrene) with the Helix‐Forming β‐1,3‐Glucan Polysaccharide

We have demonstrated that giant polymer micelles with a uniform diameter (ca. 200 nm) can be fabricated by “supramolecular wrapping” of poly(styrene) (PS) with the β‐1,3‐glucan polysaccharide, with the β‐1,3‐glucan fastening the PS chains together in a noncovalent fashion to facilitate the formation of a supramolecular polymer network on the O/W emulsion surface. Various spectroscopic and microscopic investigations have revealed that the inner cores of the micelles are comprised of a hydrophobic PS network, whereas the surfaces consist of a hydrophilic β‐1,3‐glucan layer. Accordingly, functional guest molecules can easily be encapsulated inside the cavity through hydrophobic interactions. The encapsulated molecules can simply be released from the micelle cores by peeling off the β‐1,3‐glucan shell in a supramolecular manner. As functional groups can be introduced into the glucose side‐chain unit in a straightforward manner by chemical modification, the micellar surface can acquire further functions useful for molecular recognition. These results show that the micelles obtained could have applications as novel soft nanoparticles, which would be indispensable not only for nanotechnologies, but also for biotechnologies aimed at gene or drug delivery systems.     

Physicochemical aspects of drug delivery and release from polymer-based colloids

Recent advances in the preparation/loading, surface properties, and applications of polymer-based colloidal drug delivery and release systems, such as block copolymer micelles, polymer nano- and microparticles, polymer-modified liposomes, and chemical and physical hydrogels are presented. Drug release from polymer-based systems is affected by the drug–polymer interactions as well as the polymer microstructure and dissociation/erosion properties. Surface modification with poly(ethylene oxide) has become common in improving the biocompatibility and biodistribution of drug delivery carriers. Site-specific drug delivery can be achieved by polymer-based colloidal drug carriers when ligands of targeting information are attached on the carrier surface or when a phase transition is induced by an external stimulus. While significant progress in being made, many challenges remain in preserving the biological activity and attaining the desired drug release properties, especially for protein and DNA drugs.     

Nanoscale surface patterns from 10(3) single molecule helices of biodegradable poly(L-lactic acid)

Atomic force microscopy, reflection absorption infrared spectroscopy, and X-ray reflectivity studies reveal that poly(L-lactic acid) molecules in Langmuir-Blodgett (LB) films exist as 10(3) helices over nearly the entire length of the polymer chain. This feature gives rise to LB films with highly ordered nanoscale smectic liquid crystalline-like surface patterns with low surface roughness and lamellar spacings that scale with molar mass. These studies provide a new approach for controlling surface morphology with a biodegradable polymer commonly used for drug delivery and tissue engineering.     

Redox-responsive polymer prodrug/AgNPs hybrid nanoparticles for drug delivery

The redox-responsive hybrid nanoparticles of P(MACPTS-co-MAGP)@AgNPs is developed for drug delivery and fluorescence monitoring of the drug release by applying the NSET-based strategy.