Multifunctional hybrid micelles are prepared from amphiphilic mal‐PEG‐b‐PLA and mPEG‐b‐P(LA‐co‐DHC/RhB) block copolymers. A specific anti‐transferrin receptor antibody, OX26, is linked onto the surface of the micelles. ELISA indicates that the conjugated antibody preserves its activity. OX26 conjugation can increase the uptake efficiency of micelles by target cell lines (C6). Pharmacokinetics and in vivo biodistribution experiments are carried out to investigate the ability of OX26‐conjugated micelles (immunomicelles) to cross the blood–brain barrier. The data show that the brain uptake of OX26‐conjugated micelles is much more than that of OX26‐free ones. Therefore, OX26‐conjugated micelles will be promising drug carriers to cross the blood‐brain barrier.
Novel water‐insoluble, and reduction‐responsive nonwoven scaffolds were fabricated from γ‐PGA and tested in cell culture. An electrospinning method was developed to produce scaffolds of fibers with diameters of 0.05–0.5 µm. Crosslinking of the fibers with cystamine in the presence of EDC resulted in water‐insoluble γ‐PGA nonwovens with disulfide crosslinkages. These crosslinked fibers were easily decomposed under physiological conditions using L ‐cysteine, a biocompatible reductant. In vitro experiments with mouse L929 fibroblasts showed good adhesion onto γ‐PGA‐SS fiber matrices and excellent cell proliferation. These γ‐PGA‐SS nonwovens can be used as novel biocompatible and biodegradable scaffolds with reduction‐responsiveness for biomedical or tissue engineering applications.
Block copolymer micelles with bactericidal properties were designed to deactivate pathogens such as E. coli bacteria. The micelles of PS‐b‐PAA and PS‐b‐P4VP block copolymers were loaded with biocides TCMTB or TCN up to 20 or 30 wt.‐%, depending on the type of antibacterial agent. Bacteria were exposed to loaded micelles and bacterial deactivation was evaluated. The micelles loaded with TCN are bactericidal; bacteria are killed in less than two minutes of exposure. The most likely interpretation of the data is that the biocide is transferred to the bacteria by repeated micelle/bacteria contacts, and not via the solution.
A new type of fluorescent polymeric micelles is developed by self‐assembly from a series of amphiphilic block copolymers, poly(ethylene glycol)‐b‐poly[styrene‐co‐(2‐(1,2,3,4,5‐pentaphenyl‐1H‐silol‐1‐yloxy)ethyl methacrylate)] [PEG‐b‐P(S‐co‐PPSEMA)]. Their capability of loading doxorubicin (DOX) is investigated by monitoring the loading content, encapsulation efficiency, and photophysical properties of micelles. Förster resonance energy transfer from PPSEMA to DOX is observed in DOX‐loaded micelles, which can serve as an indication of successful encapsulation of DOX in these micelles. The application of this new type of fluorescent polymeric micelles as a fluorescent probe and an anticancer drug carrier simultaneously is explored by studying the intracellular uptake of DOX‐loaded micelles.
The title compounds 10 and 11 were prepared by a one‐step procedure from 1,4‐benzoquinone ( 4 ) and pyridine‐2,4,6‐triamine ( 5 ) via an extension of the Nenitzescu reaction 相似文献
Comb‐shaped glycopolymer/peptide bioconjugates are constructed by grafting reduced glutathione (GSH) onto acrylate‐functional block glycocopolymers via thiol‐ene click chemistry. In aqueous solution, the glycopolymer/GSH bioconjugate self‐assembles to sugar‐installed spherical micelles. The size of micelles decreases with increasing pH, demonstrating pH‐responsive character. The isoelectric point (IEP) of the PMAGlc/GSH bioconjugate is estimated to be 3.43. The micelles show a specific interaction with the protein Concanavalin A. At endosomal pH, the PMAGlc/GSH bioconjugate can gradually degrade. These pH‐responsive glycopolymer/peptide micelles with biological recognition and degradation can be used as multifunctional nanocarriers for targeted drug delivery.
Poly(dimethylsiloxane)‐block‐poly(methyl methacrylate)‐block‐poly(2,2,3,3,4,4,4‐heptafluorobutyl methacrylate) was successfully synthesized via ATRP. The chemical composition and structure of the copolymer was characterized by NMR and FT‐IR spectroscopy and molecular weight measurement. Gel permeation chromatography was used to study the molecular weight distribution of the triblock copolymer. The surface properties of the resulting copolymer were investigated. The effects of fluorine content and bulk structure on surface energy were investigated by static water contact angle measurements. Surface composition was studied by XPS.
A new type of pH‐responsive block copolymer nanoparticle has been synthesized and characterized. The amphiphilic diblock copolymer, PEG‐b‐PMYM, contains acid‐labile ortho ester side‐chains in the hydrophobic block and can self‐assemble into micelle‐like nanoparticles in water at neutral pH. Hydrolysis of the ortho ester side‐chains follows a distinct exocyclic mechanism and shows pH‐dependent kinetics, which triggers changes in nanoparticle size and morphology. The nanoparticles have been found to be non‐toxic to cells in vitro. The ability to tune the size and morphology of biocompatible block copolymer nanoparticles by controlling the pH‐sensitive side‐chain hydrolysis represents a unique approach that may be exploited to improve the efficacy of nanometer‐scale drug delivery.
Thiolated Pluronic (Plu‐SH) nanoparticles are developed as potential articulate, target‐specific anticancer‐drug carriers for intracellular drug release triggered by the difference in redox potential in tumor cells. The cores of the micelles are formed by the disulfide bonds of the functionalized Pluronic F127, when dissolved in an aqueous solution. The nanoparticles are 95.6 ± 18.6 nm in size, and 235.6 ± 63.7 nm after encapsulation of the hydrophobic drug molecules. The drug‐loaded micelles show effective stability in blood‐plasma conditions and the kinetics of micelle stability and drug release are shown. Paclitaxel‐loaded micelles display approximately 39% cell viability in A549 cells.
A pH‐sensitive polymer was synthesized by introducing the N‐Boc‐histidine to the ends of a PLGA‐PEG‐PLGA block copolymer. The synthesized polymer was confirmed to be biodegradable and biocompatible, well dissolved in water and forming micelles above the CMC. DOX was employed as a model anticancer drug. In vitro drug release from micelles of N‐Boc‐histidine‐capped PLGA‐PEG‐PLGA exhibited significant difference between pH = 6.2 and pH = 7.4, whereas DOX release from micelles composed of un‐capped virgin polymers was not significantly sensitive to medium pH. Uptake of DOX from micelles of the new polymer into MDA‐MB‐435 solid tumor cells was also observed, and pH sensitivity was confirmed. Hence, the N‐Boc‐histidine capped PLGA‐PEG‐PLGA might be a promising material for tumor targeting.
Bio‐based fibrous nanocomposites of cellulose nanofibres and non‐crosslinked/crosslinked collagen were prepared by in situ pH‐induced fibrillation of collagen phase and sterilized using gamma rays at 25 KGy. Collagen phase is crosslinked using genipin, a bio‐based crosslinker that introduces flexible crosslinks. Microscopy studies of the prepared materials showed nanostructured fibrous collagen and cellulose dispersed in collagen matrix. Mechanical performance of the sterilized nanocomposites was close to that of natural ligament and tendon, in simulated body conditions. Cytocompatibility studies indicated that these nanocomposites allowed human ligament cell and human endothelial cell adhesion, growth, and differentiation; which is eminently favourable to ligament tissue engineering.
We developed a mathematical model to describe the solution polymerization of olefins with two single‐site catalysts in a series of two CSTRs. The model was used to simulate processes where semi‐crystalline macromonomers produced in the first reactor are incorporated as long chain branches onto amorphous (or lower crystallinity) chains in the second reactor (cross‐products). The simulation results show that CSTRs are more efficient to make chains with high LCB density and high weight percent of cross‐products. The model can also predict the polydispersity index, average chain lengths, and fractions of the different polymer populations, and help the polymer reactor engineer formulate new products with complex microstructures.
None of the replacements proposed in the literature for small‐calibre blood vessels (SCBV) fully satisfies the stringent requirements that these grafts have to fulfil. Here, an electrospun silk fibroin tubular construct is hybridized with type I collagen gel to produce a biomimetic SCBV graft with physiologically relevant compliance and burst pressure and optimal cytocompatibility. The hybridization of the two polymers results in the formation of a nanofibrillar hydrated matrix, where the collagen gel enhances the mechanical properties of the SF tubular construct and improves the early response of the material to in vitro cell adhesion and proliferation.
New delivery approaches to achieve minimally invasive, sustained and local release of drugs are needed for more effective treatment of conditions such as cancer and ischemia. Hydrophobic, biodegradable, liquid injectable polymers possess a number of potential advantages for this purpose. This review examines various approaches that have been explored for the preparation of these types of polymers, their ability to control the release of various drugs ranging from low‐molecular‐weight hydrophobic compounds to protein therapeutics, and finally their degradation rates and the tissue response to them upon implantation.
