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.
CDDP is loaded into methoxypoly(ethylene glycol)‐block‐poly(L ‐glutamic acid) (mPEG‐b‐PLG), and a combination with iRGD is applied for NSCLC chemotherapy. The CDDP‐loaded micelles show sustained cisplatin release in PBS, dose‐ and time‐dependent inhibition to HeLa and A549 cell proliferation, and no apparent hemolysis activities. In in vivo studies using subcutaneous NSCLC xenograft models (A549), both free CDDP and CDDP‐loaded micelles show an evident anti‐tumor effect. However, the toxicity of CDDP is significantly reduced in the cases of CDDP‐loaded micelles and co‐administration with iRGD, and the survival time is prolonged by over 30%. Therefore, mPEG‐b‐PLG‐loaded cisplatin and the combination with iRGD provides a promising new therapy for NSCLC.
A new approach to engineer a local drug delivery system with delayed release using nanostructured surface with nanotube arrays is presented. TNT arrays electrochemically generated on a titanium surface are used as a model substrate. Polymer micelles as drug carriers encapsulated with drug are loaded at the bottom of the TNT structure and their delayed release is obtained by loading blank micelles (without drug) on the top. The delayed and time‐controlled drug release is successfully demonstrated by controlling the ratio of blank and drug loaded‐micelles. The concept is verified using four different polymer micelles (regular and inverted) loaded with water‐insoluble (indomethacin) and water‐soluble drugs (gentamicin).
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.
The 3D spatial structure of porous polyethylene particles was reconstructed from their X‐ray micro‐tomography images. Several polyolefin particles with an artificial granular structure were generated. Transport in reconstructed particles was calculated for the case of a monomer diffusing through both the pores and the polymer. The calculated degassing characteristics of reconstructed polyolefin particles can be compared to experiments. Monomer mass transport limitations are important not only in the early stage of particle growth, but also in fully‐developed polyolefin particles. The problems and limitations of the developed method are discussed. The method developed allows prediction of the effect of particle structure on mass transport limitations for real particle structures.
Thermosensitive PNVCL‐b‐PEG block copolymer coupled with folic acid was prepared as an anti‐cancer drug carrier. This polymer self‐assembled into stable micelles in aqueous solutions at above 33 °C. At 37 °C, the release profile of PNVCL‐b‐PEG‐FA micelles showed a slower and more controlled release of the entrapped 5‐FU than that at 25 °C. The blank and 5‐FU‐loaded PNVCL‐b‐PEG‐FA micelles did not induce remarkable cytotoxicity against the EA.hy 926 human endothelial cell line; however, 5‐FU‐loaded PNVCL‐b‐PEG‐FA micelles showed a cytotoxicity effect against 4T1 mouse mammary carcinoma cells due to the availability of loaded anti‐cancer drugs delivered to the inside of the cancer cells by the folate‐receptor‐mediated endocytosis process.
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.
The development of thermo‐responsive and reduction‐sensitive polymeric micelles based on an amphiphilic block copolymer poly[(PEG‐MEMA)‐co‐(Boc‐Cyst‐MMAm)]‐block‐PEG (denoted PEG‐P‐SS‐HP) for the intracellular delivery of anticancer drugs is reported. PTX, as model drug, was loaded into the PEG‐P‐SS‐HP micelles with an encapsulation efficiency >90%, resulting in a high drug loading content (up to 35 wt%). The PTX‐loaded PEG‐P‐SS‐HP micelles show slow drug release in PBS and rapid release after incubation with DTT. The PTX‐loaded micelles display a better cytotoxic effect than the free drug, whereas empty micelles are found to be non‐toxic. The thermo‐responsive and reduction‐sensitive polymeric micelles described may serve as promising carriers for cytostatic drugs.
A biodegradable amphiphilic block copolymer, PEG‐b‐P(LA‐co‐MAC), was used to prepare spherical micelles consisting of a hydrophobic P(LA‐co‐MAC) core and a hydrophilic PEG shell. To improve their stability, the micelles were crosslinked by radical polymerization of the double bonds in the hydrophobic blocks. The crosslinked micelles had similar sizes and a narrow size distribution compared to their uncrosslinked precursor. The improved stability of the crosslinked micelles was confirmed by measurements of the CMC and a thermodynamic investigation. These micelles can internalize into Hela cells in vitro as demonstrated by inverted fluorescence microscopy and CLSM. These stabilized nanoscale micelles have potential use in biomedical applications such as drug delivery and disease diagnosis.
Some bisheterocycles having pyrrole and oxazoline/thiazoline units were synthesized from Z‐styrylsulfonylacetic acid methyl esters using samarium chloride. 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.
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.
Research and development in the design, synthesis, modification, evaluation, and characterization of polysaccharide‐based bioactive polymeric materials for guiding and promoting new tissue in‐growth is reviewed. Emphasis is given in this interdisciplinary field of tissue engineering (TE) with particular reference to bone, cartilage, and skin TE. Current strategies in scaffold‐guided TE approaches using polymers of natural origin and their composites are elaborated. Innovative modification techniques in creating functional materials for advanced TE applications are presented. Challenges and possible solutions in the technological innovation in factor molecules incorporation and surface functionalization for improving the fabrication of biomaterials scaffolds for cost‐effective TE are also presented.
The design of a novel polymer‐modified overlayer composed of PPAPE and GPMS on a silicon wafer for immobilization of DNA molecules is described. After hydroxylation of Si(100) surfaces, GPMS molecules were self‐assembled onto these surfaces. PPAPE molecules were then covalently attached to the epoxy‐terminated surfaces. The incubation time and concentration of PPAPE was found to effect both layer thickness and water CA. The type of organic solvent and the pH were found to change the nature of the PPAPE‐modified surface for DNA immobilization. It is concluded that PPAPE‐modified surfaces show advantages for DNA immobilization by electrostatic interactions between DNA molecules and positively charged free amino groups of the PPAPE‐modified surfaces at the appropriate pH values.
Novel ‘nano in nano’ composites consisting of biodegradable polymer nanoparticles incorporated into polymer nanofibers may efficiently modulate drug delivery. This is shown here using a combination of model compound‐loaded biodegradable nanoparticles encapsulated in electrospun fibers. The dye coumarin 6 is used as model compound for a drug in order to simulate drug release from loaded poly(lactide‐co‐glycolide) nanoparticles. Dye release from the nanoparticles occurs immediately in aqueous solution. Dye‐loaded nanoparticles which are encapsulated by electrospun polymer nanofibers display a significantly retarded release.
Water‐soluble, PAX‐loaded carbon nanotubes are fabricated by employing a synthetic polyampholyte, PDM. To investigate the suitability of the polyampholyte and the nanotubes as drug carriers, different cellular interactions such as the human epithelial Caco‐2 cells viability, their effect on the cell growth, and the change in the transepithelial electrical resistance in Caco‐2 cells are studied. The resulting complex is found to exhibit an effective anti‐cancer effect against colon cancer cells and an increased the reduction of the electrical resistance in the Caco‐2 cells when compared to the precursor PAX.
