Preparation of Functionalized Polymersomes and the In Vivo Imaging

Recently, polymersomes self-assembled from amphiphilic block copolymers have attracted considerable interests with superior physicochemical properties. Here, the biotinylated block copolymers were blended with unmodified block copolymers to produce biotinylated polymersomes via film rehydration. Then, the avidin molecules were attached onto the biotin molecules covalently linked with block copolymers to form surface functionalized vesicles that are capable of carrying various biotinylated bioactive molecules, generating a relatively universal delivery platform. Hydrophobic fluorophores DAF and Nile Red were encapsulated respectively into hydrophobic membrane to prepare hydrophobic substances loaded polymersomes for investigating the nature of hydrophobic functionalization. Furthermore, the hydrophobic functionalized DiR-polymersomes were employed to perform in vivo imaging to survey the in vivo behavior for nano-polymersomes with hydrophobic functionalization.     

Synthesis and functionalization of nanoengineered materials using click chemistry

The synthesis of nanoengineered materials with precise control over material composition, architecture and functionality is integral to advances in diverse fields, including biomedicine. Over the last 10 years, click chemistry has emerged as a prominent and versatile approach to engineer materials with specific properties. Herein, we highlight the application of click chemistry for the synthesis of nanoengineered materials, ranging from ultrathin films to delivery systems such as polymersomes, dendrimers and capsules. In addition, we discuss the use of click chemistry for functionalizing such materials, focusing on modifications aimed at biomedical applications.     

Polymeric nanostructured materials for biomedical applications

Polymeric nanostructured materials (PNMs), which are polymeric materials in nanoscale or polymer composites containing nanomaterials, have become increasingly useful for biomedical applications. In specific, advances in polymer-related nanoscience and nanotechnology have brought a revolutionary change to produce new biomaterials with tailored properties and functionalities for targeted biomedical applications. These materials, including micelles, polymersomes, nanoparticles, nanocapsules, nanogels, nanofibers, dendrimers and nanocomposites, have been widely used in drug delivery, gene therapy, bioimage, tissue engineering and regenerative medicine. This review presents a comprehensive overview on the various types of PNMs, their fabrication methods and biomedical applications, as well as the challenges in research and development of future PNMs.     

Polymeric nanoparticles,micelles and polymersomes from amphiphilic block copolymer

Block copolymers are made up of blocks of different polymerized monomers. Among the block copolymers, amphiphilic block copolymers can self-assemble to form nano-sized vehicles, such as micelles, nanoparticles, polymersomes, in aqueous or non-aqueous media. This review describes the synthesis, formation, and major applications of amphiphilic block copolymer and corresponding vehicles in order to provide an overview of the current features of functionalized block copolymers for drug delivery applications.     

Functional dendrimer–gold nanoparticle hybrids for biomedical applications

Dendrimers are a class of nano‐sized synthetic polymers with a well‐defined composition and regularly branched tree‐like structure produced by stepwise growth. The uniform size, globular shape and tunable surface chemistry make dendrimers versatile nanoscaffolds to encapsulate or stabilize various inorganic (metal, metal oxide, semiconductor) nanoparticles. In the past decade, research interest in dendrimer–inorganic nanoparticle hybrids has evolved from the development of interesting properties to the exploitation of advanced and useful functions. In particular, because gold nanoparticles with controlled morphology and optical properties have been demonstrated to be promising and versatile candidates for a diverse field of biomedical applications including sensing, in vitro and in vivo imaging, drug delivery, diagnostics and therapies, dendrimer–gold nanoparticle hybrids with biocompatibility have recently been intensively investigated for promising biomedical applications due to their controllable structures and dimensions, as well as their desirable internal and/or external functionalities. In this review, we discuss the recent progress regarding the development of functional dendrimer–gold nanoparticle hybrids for biomedical applications. The strategies for the fabrication of various structures of dendrimer–gold nanoparticle hybrids will first be summarized, followed by their biomedical applications in drug and gene delivery, photothermal therapy and combined therapies. © 2018 Society of Chemical Industry     

Biodegradable polymersomes from four‐arm PEG‐b‐PDLLA for encapsulating hemoglobin

A series of four‐arm star block copolymers poly(ethylene glycol)‐block‐poly(d,l ‐lactide) (PEG‐PDLLA) with different hydrophobic length were synthesized by ring‐opening polymerization of lactide and characterized using ¹H NMR and gel permeation chromatography (GPC). These copolymers could self‐assemble in aqueous solution to form the vesicle structure with controlled size and morphologies. Transmission electron microscopy (TEM) and DLS show the polymersomes are spherical with diameter of 70～500 nm. The polymersomes made by direct hydration of copolymer thin films in water exhibit the controllable ability of encapsulating hemoglobin under mild condition. The hemoglobin content in the polymersomes could reach to 35 wt %. More importantly, the encapsulated hemoglobin keeps its own bioactivity and is capable of binding oxygen. This hemoglobin‐encapsulated four‐arm PEG‐PLA polymersomes could have the potential to be applied as an artificial oxygen carrier for transfusion. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40433.     

Amphiphilic diblock and crosslinked copolymers synthesized via metal‐free atom transfer radical polymerization

The use of metal‐free atom transfer radical polymerization (MF‐ATRP) was explored for the formation of diverse macromolecular structures to assess the versatility of this advanced polymerization process. In MF‐ATRP using an organic photocatalyst, 10‐phenylphenothiazine, the influences of various monomers, initiators and solvents were examined, showing that molecular weight and polydispersity could be tailored through appropriate selection of each component. Using this modern polymerization technology, metal‐free amphiphilic diblock and crosslinked copolymers were prepared successfully. Especially, demonstration of amphiphilic diblock copolymer synthesis provides a basis for further applications to biomedical materials. © 2017 Society of Chemical Industry     

Modular Manufacturing Platform for Continuous Synthesis and Analysis of Versatile Nanomaterials

Nanoparticular materials have a great potential in various fields including technical and biomedical applications; to meet the specific requirements, a good control over the particle characteristics is mandatory. Addressing this, a modular system for the automated and continuous synthesis, workup, and analysis of a broad range of nanoparticles was developed. Application examples of inorganic (silica) and organic (polymersomes, niosomes) nanoparticles demonstrate the versatility of the production platform. Modules for downstream processing via a falling‐film microreactor or tangential flow filtration are presented. The hydrodynamic size as a key parameter is acquired in real time, with an inline dynamic light scattering device. All modules are controlled and operated by a process control system.     

Modification of Poly(Vinyl Chloride) for Biocompatibility Improvement and Biomedical Application-Review

Poly(vinyl chloride) is widely used in biomedical devices. This review deals with various applications of PVC and modified PVC in the medical field. Blended, grafted, and plasma-treated modified PVCs are described for various medical applications. Plasma treatment of PVC devices is a versatile and useful method for changing the surface properties, as compared to blending and grafting.     

Emerging Perspectives in the Synthesis of Novel Degradable Biomedical Copolymers

Biodegradable polymer is playing an increasingly significant role in the development of biomedical materials due to its good biocompatibility and biodegradability, and is undoubtedly the focus in the biomedical fields, such as controlled drug delivery, tissue engineering, and regenerative medicine. In this review, some new degradable biomedical copolymers reported over the past 5 years are introduced and discussed in combination with some our research results. The molecular design, chemical structures and related properties of these novel biodegradable copolymers are reported. In summarizing the review, the development, potential applications and future directions of the degradable biomedical copolymers are discussed.     

Biodegradable Polyurethane Elastomers for Biomedical Applications – Synthesis Methods and Properties

Biodegradable polyurethane elastomers (BioEPUR) are becoming increasingly important as biomaterials because they have excellent chemical, physico-mechanical and biological properties. This review presents the recent developments on BioEPUR and their potential applications in the biomedical and pharmaceutical fields. The aim of this work is to present an overview of the various methods of synthesis and properties of biomedical BioEPUR. Polyurethanes-based aliphatic or cycloaliphatic diisocyanates and polyesters, poly(ester-carbonate)s or copolymers of heterocyclic monomers were discussed.     

Biodegradable synthetic polymers: Preparation, functionalization and biomedical application

Biodegradable polymers have been widely used and have greatly promoted the development of biomedical fields because of their biocompatibility and biodegradability. The development of biotechnology and medical technology has set higher requirements for biomedical materials. Novel biodegradable polymers with specific properties are in great demand. Biodegradable polymers can be classified as natural or synthetic polymers according to the source. Synthetic biodegradable polymers have found more versatile and diverse biomedical applications owing to their tailorable designs or modifications. This review presents a comprehensive introduction to various types of synthetic biodegradable polymers with reactive groups and bioactive groups, and further describes their structure, preparation procedures and properties. The focus is on advances in the past decade in functionalization and responsive strategies of biodegradable polymers and their biomedical applications. The possible future developments of the materials are also discussed.     

Well-defined phosphonated homo- and copolymers via direct ring opening metathesis polymerization

Phosphonated polymers with a well-defined molecular weight, composition and architecture have been prepared via ring opening metathesis polymerization (ROMP) of phosphonated and non-phosphonated norbornene imides at room temperature for the first time. ROMP was proven to be living and versatile. This enabled preparation of a broad range of phosphonated homopolymers, statistical copolymers, AB diblock as well as ABA and BAB triblock copolymers based on poly(norbornene imide)s with low polydispersity (1.09–1.32). Complete hydrolysis of phosphonated poly(norbornene imide)s under mild conditions yielded the phosphonic acid derivatives. Thermogravimetric analysis indicated high thermal and thermo-oxidative stability of the polymers. Free standing and transparent films with good mechanical stability were obtained from the phosphonic acid functional homopolymers, diblock and triblock copolymers. Combining these basic properties with the advantages mentioned above makes ROMP a promising pathway for accessing a wide diversity of phosphonated macromolecular structures. These new phosphonated polymers will open new perspectives in advanced application areas, which require a high level of control over polymer structure.     

Microfluidics for producing polylactide nanoparticles and microparticles and their drug delivery application

This review presents use of the microfluidics technique for the preparation of polylactide (PLA) based particles for developing novel drug delivery systems. Droplet‐based microfluidics allow uniform single, double and higher order emulsions to be generated that yield highly uniform microspheres, microcapsules and polymersomes. Typically, the building blocks of these complex microparticle systems are PLA macromolecules, their copolymers with different comonomers and recently stereocomplexes composed of an equimolar mixture of poly(l ‐lactide) and poly(d ‐lactide). In addition, the technique offers several advantages over conventional emulsion methods and the highly uniform droplets obtained allow for encapsulation of small drug molecules in polymer network meshes or within their hollow interior. The novel approach in this area is to use the microfluidics technique to produce nanoparticles in the microfluidics channel by micromixing/nanoprecipitation in glass capillary devices. Therefore, this review is divided into three main sections in which we discuss the formation of microspheres from single emulsion droplets, microcapsules and polymersomes from higher order emulsion droplets, and nanoparticles from nanosuspensions in a microfluidic channel. Finally, we compare the drug release from these different particles, focusing mainly on those formed from sensitive or supramolecular networks. © 2018 Society of Chemical Industry     

Design and synthesis of perfluorinated amphiphilic copolymers: Smart nanomicelles for theranostic applications

Since decades, varieties of amphiphilic polymers have been widely investigated for improving aqueous solubility and bioavailability of the hydrophobic drugs. The upcoming approach is to develop more efficient advanced nano-carrier molecules capable of more than drug delivery. Herein, we report the design and synthesis of some novel carrier molecules with multiple applications including drug encapsulation, drug delivery and diagnosis (imaging). Copolymers were synthesized using dimethyl 5-hydroxy/aminoisophthalate, poly(ethylene glycols) and Candida antarctica lipase (CAL-B, Novozym 435). CAL-B selectively catalyses the trans esterification reaction under solvent less condition using primary hydroxyls of poly(ethylene glycols) and leaving behind phenolic hydroxyl for post polymerization modifications. The obtained copolymers were further tethered with perfluorinated aliphatic chains to make them amphiphilic. The synthesized materials were investigated for their micellar behavior, temperature dependent stability (in aqueous solution), encapsulation capacity, and imaging potential by measuring the sensitivity of these perfluorinated materials towards ¹⁹F NMR in NMR tube. It was observed that perfluorinated amphiphilic copolymers could encapsulate up to 14% (by wt) of hydrophobic drug and showed decent ¹⁹F NMR signals even at a very low concentration. Therefore, these perfluorinated copolymers hold considerable potential for further investigation as advanced nano-carrier molecules for biomedical applications.     

原子转移自由基聚合法接枝改性纳米纤维素及其功能化应用

纳米纤维素不仅具有天然纤维素的基本结构和特性,还具有纳米粒子的独特性能,使其成为众多领域的研究热点。然而,由于纳米纤维素表面存在丰富的羟基,导致表面化学性质单一,需要对其进行化学改性拓宽应用领域。原子转移自由基聚合法(ATRP)能够对纳米纤维素表面进行接枝改性,从而赋予纳米纤维素多样化的功能特性,是纳米纤维素高值化应用的重要方法。本文首先总结了传统ATRP法以及四种新型ATRP法在纳米纤维素表面接枝改性中的应用进展;随后介绍了ATRP法在纳米纤维素端基接枝改性中的应用进展;然后分别介绍了ATRP改性的纳米纤维素接枝共聚物在纳米复合增强、智能响应、环保和生物医疗等领域的应用研究;最后总结了ATRP法改性纳米纤维素存在的难点,并展望了未来ATRP法在纳米纤维素接枝改性领域的发展趋势。     

Synthesis and characterization of poly(L‐lactide)‐poly(ethylene glycol) multiblock copolymers

Poly(L‐lactide)‐poly(ethylene glycol) multiblock copolymers with predetermined block lengths were synthesized by polycondensation of PLA diols and PEG diacids. The reaction was carried out under mild conditions, using dicyclohexylcarbodiimide as the coupling agent and dimethylaminopyridine as the catalyst. The resulting copolymers were characterized by various analytical techniques, such as GPC, viscometry, ¹H‐NMR, FTIR, DSC, X‐ray diffractometry, and contact angle measurement. The results indicated that these copolymers presented outstanding properties pertinent to biomedical use, including better miscibility between the two components, low crystallinity, and hydrophilicity. Moreover, the properties of the copolymers can be modulated by adjusting the block length of the two components or the reaction conditions. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 84: 1729–1736, 2002; DOI 10.1002/app.10580     

Application‐directed syntheses of surface‐functionalized organic and inorganic nanoparticles

An overview of the formation of inorganic and organic particles in emulsions is presented. The key aspect in these syntheses is the use of specially designed surface‐active components. Examples of synthesis‐driven approaches to various functional nanoparticles are illustrated. Surfmers based on isophthalic acid give access to particles for highly stabilized emulsions. Amphiphilic block copolymers as emulsifiers result in particles with excellent film‐forming properties or which are applicable as supports for metallocenes. Amphiphilic statistical copolymers are used for the compatibilization of inorganic nanoparticles in hybrid materials. Block and statistical copolymers are versatile stabilizers of non‐aqueous emulsions. In such systems nanoparticles obtained by either water‐sensitive monomers or catalysts can be realized. Surface functionalization with aliphatic or aromatic amines results in latex particles, which are suitable as supports for postmetallocenes or as flocculants in the papermaking process. In each area, the incorporation of the amphiphiles at the nanoparticle surface is not only important for the particle formation itself, but also decisive for the applicability of the particles. Copyright © 2007 Society of Chemical Industry     

Photomediated controlled radical polymerization

Photomediated controlled radical polymerization is a versatile method to prepare, under mild conditions, various well-defined polymers with complex architecture, such as block and graft copolymers, sequence-controlled polymers, or hybrid materials via surface-initiated polymerization. It also provides opportunity to manipulate the reaction through spatiotemporal control. This review presents a comprehensive account of the fundamentals and applications of various photomediated CRP techniques, including atom transfer radical polymerization (ATRP), reversible addition-fragmentation chain transfer (RAFT), nitroxide mediated polymerization (NMP) and other procedures. In addition, mechanistic aspects of other photomediated methods are discussed.     

Solution styrene butadiene copolymers with lithium alkyl initiators

This paper is a review of the alkyllithium system of the copolymerization of butadiene and styrene. The alkyllithium system offer a very versatile tool by which a wide variety of styrene butadiene copolymers can be made to fit a particular application. Included are discussions of block and non-block copolymers of styrene butadiene, copolymers with functional groups, and copolymers with varying microstructure. In addition, wear and tractuion on a series of styrene butadiene copolymers with varying content and microstructure are presented.