Zhengpu Zhang

Nankai University, Tianjin, Tianjin Shi, China

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Publications (12)42.07 Total impact

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    ABSTRACT: Nasal drug delivery system has been a very promising route for delivery of proteins and peptides for the reason that it can avoid degradation in gastrointestinal tract and metabolism by liver enzymes. However, the bioavailability of proteins and peptides is still low due to the rapid clearance of mucociliary. Here, to prolong the residence time of drugs and improve their absorption, we prepared amphiphilic glycopolymer poly(2-lactobionamidoethyl methacrylate-random-3-acrylamidophenylboronic acid) (p(LAMA-r-AAPBA), and the glycopolymer could assemble into the nanoparticles with narrow size distribution. Insulin, as a model drug, was efficiently encapsulated within the nanoparticles, and loading capacity was up to 12%. In vitro study revealed that the insulin release could be controlled by modifying the composition of glycopolymers. Cell viability showed that p(LAMA-r-AAPBA) nanoparticles had good cytocompatibility. Moreover, the mechanism of nanoparticle internalization into Calu-3 cells was a combination mechanism of clathrin-mediated endocytosis and lipid raft/caveolae-mediated endocytosis. Importantly, there was a significant decrease in the blood glucose levels after the nasal administration of p(LAMA-r-AAPBA) nanoparticles to diabetic rats. Therefore, p(LAMA-r-AAPBA) glycopolymers have a potential application as a nasal delivery systems for proteins and peptides.
    European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 05/2013; · 2.61 Impact Factor
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    ABSTRACT: Star-shaped polymers provide more terminal groups, and are promising for application in drug-delivery systems. A new series of six-arm star-shaped poly(lactic-co-glycolic acid) (6-s-PLGA) was synthesized by ring-opening polymerization. The structure and properties of the 6-s-PLGA were characterized by carbon-13 nuclear magnetic resonance spectroscopy, infrared spectroscopy, gel permeation chromatography, and differential scanning calorimetry. Then, paclitaxel-loaded six-arm star-shaped poly(lactic-co-glycolic acid) nanoparticles (6-s-PLGA-PTX-NPs) were prepared under the conditions optimized by the orthogonal testing. High-performance liquid chromatography was used to analyze the nanoparticles' encapsulation efficiency and drug-loading capacity, dynamic light scattering was used to determine their size and size distribution, and transmission electron microscopy was used to evaluate their morphology. The release performance of the 6-s-PLGA-PTX-NPs in vitro and the cytostatic effect of 6-s-PLGA-PTX-NPs were investigated in comparison with paclitaxel-loaded linear poly(lactic-co-glycolic acid) nanoparticles (L-PLGA-PTX-NPs). The results of carbon-13 nuclear magnetic resonance spectroscopy and infrared spectroscopy suggest that the polymerization was successfully initiated by inositol and confirm the structure of 6-s-PLGA. The molecular weights of a series of 6-s-PLGAs had a ratio corresponding to the molar ratio of raw materials to initiator. Differential scanning calorimetry revealed that the 6-s-PLGA had a low glass transition temperature of 40°C-50°C. The 6-s-PLGA-PTX-NPs were monodispersed with an average diameter of 240.4±6.9 nm in water, which was further confirmed by transmission electron microscopy. The encapsulation efficiency of the 6-s-PLGA-PTX-NPs was higher than that of the L-PLGA-PTX-NPs. In terms of the in vitro release of nanoparticles, paclitaxel (PTX) was released more slowly and more steadily from 6-s-PLGA than from linear poly(lactic-co-glycolic acid). In the cytostatic study, the 6-s-PLGA-PTX-NPs and L-PLGA-PTX-NPs were found to have a similar antiproliferative effect, which indicates durable efficacy due to the slower release of the PTX when loaded in 6-s-PLGA. The results suggest that 6-s-PLGA may be promising for application in PTX delivery to enhance sustained antiproliferative therapy.
    International Journal of Nanomedicine 01/2013; 8:4315-26. · 4.20 Impact Factor
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    ABSTRACT: A novel functional diblock polymer P(PEGMA-b-MAH) is prepared and incorporated to improve the gene delivery efficiency of poly(ethyleneimine) PEI via non-covalent assembly strategy. First, P(PEGMA-b-MAH) is prepared from l-methacrylamidohistidine methyl ester (MAH) by reversible addition fragmentation chain transfer polymerization, with poly[poly(ethylene glycol) methyl ether methacrylate] (P(PEGMA)) as the macroinitiator. Then P(PEGMA-b-MAH) is assembled with plasmid DNA (pDNA) and PEI (M(w)=10kDa) to form PEI/P(PEGMA-b-MAH)/pDNA ternary complexes. The agarose gel retardation assay shows that the presence of P(PEGMA-b-MAH) does not interfere with DNA condensation by the PEI. Dynamic light scattering tests show that PEI/P(PEGMA-b-MAH)/pDNA ternary complexes have excellent serum stability. In vitro transfection indicates that, compared to the P(PEGMA-b-MAH) free PEI-25k/pDNA binary complexes, PEI-10k/P(PEGMA-b-MAH)/pDNA ternary complexes have lower cytotoxicity and higher gene transfection efficiency, especially under serum conditions. The ternary complexes proposed here can inspire a new strategy for the development of gene and drug delivery vectors.
    Acta biomaterialia 10/2012; · 5.68 Impact Factor
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    ABSTRACT: The grafting modified chitosan with l-glutathione (GSH) end capped PEG brush-like poly [poly(ethylene glycol) methacrylate] (PMPEG), CS-PMPEG-GSH, as the pDNA condensed vector material could result in a much higher transfection efficiency and lower cytotoxity for NIH3T3 cells. In this work, we have further examined the morphology stabilities of CS-PMPEG-GSH/pDNA vectors at different medium pH values and in the presence of serum protein in detail. And then the targeted characters for HepG2 cells have been probed by tracing the cell uptake behavior and transfection efficiency.
    Carbohydrate Polymers 06/2012; 89(1):46–53. · 3.92 Impact Factor
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    ABSTRACT: Poly(L-lysine) (PLL) is a kind of biocompatible and biodegradable polycation and can effectively condense plasmid DNA (pDNA) to form nano-scaled complexes. However, the ultra-low gene transfection efficiency limits its wide application in gene delivery. Here, an uncharged functional polymer P(His-co-DMAEL) is synthesized by reversible addition fragmentation transfer (RAFT) polymerization and characterized with 1H NMR spectrum and size exclusion chromatography (SEC). P(His-co-DMAEL) is assembled with pDNA and PLL to form PLL/pDNA/P(His-co-DMAEL) ternary complexes. Gel shift assays and dynamic light scattering (DLS) tests indicate that the stability of PLL/pDNA/P(His-co-DMAEL) ternary complexes under various conditions is much better than that of PLL/pDNA binary complexes. In vitro transfection shows that the gene transfection efficiency of PLL/pDNA/P(His-co-DMAEL) ternary complexes is much higher than that of PLL/pDNA counterparts and the “gold standard” of gene transfection, poly(ethyleneimine)/pDNA (PEI/pDNA) complexes, especially under serum conditions. Cytotoxicity assays show that PLL/pDNA/P(His-co-DMAEL) ternary complexes have no cytotoxicity. The ternary complexes have advanced the application of PLL as a gene carrier and will have enlightening significance for the development of novel gene and drug delivery carriers.
    Journal of Materials Chemistry 05/2012; 22(21):10743-10751. · 6.63 Impact Factor
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    ABSTRACT: A novel multifunctional oligomer is synthesized and incorporated to enhance the gene delivery efficiency of PLL via non-electrostatic assembly and covalent grafting strategies. The improvement of the gene delivery efficiency is dependent on the gene carrying complex properties, and the properties are dependent on the oligomer incorporation strategy.
    Chemical Communications 04/2012; 48(38):4594-6. · 6.38 Impact Factor
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    ABSTRACT: Poly(L-lysine) (PLL) has excellent plasmid DNA (pDNA) condensation capacity. However, the relatively high cytotoxicity and low transfection efficiency limit its application as gene delivery vectors. Here, well-defined glycopolymers are synthesized by reversible addition fragmentation transfer polymerization and grafted onto PLL to improve the gene delivery performance. After glycopolymer modification, PLL shows reduced cytotoxicity. By regulating the glycopolymer length and amino group substitution degree, the glycopolymer modified PLL can condense pDNA with proper strength, protect the condensed pDNA from degradation and release them in time. Transfection with NIH3T3 and HepG2 cells shows that the glycopolymer modified PLL has improved transfection efficiencies. The low cytotoxicity, effective pDNA protection and enhanced transfection efficiencies indicate that glycopolymer modification would be an effective strategy to improve the polycation properties for gene delivery.
    International journal of biological macromolecules 02/2012; 50(4):965-73. · 2.37 Impact Factor
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    ABSTRACT: The star-shaped poly (lactide-co-glycolide) (PLGA) was synthesized via the ring-opening polymerization of d,l-lactide and glycolide, with pentaerythritol as a multifunctional initiator and stannous 2-ethyl hexanoate as a catalyst. The structures of these polymers were characterized by 13C-NMR spectroscopy, while the molecular weight and polydispersity index (PDI) were determined by gel permeation chromatography (GPC). The glass transition temperature (T g) of copolymer was determined by differential scanning calorimetry (DSC). Bovine serum albumin (BSA) loaded microspheres were fabricated using star-shaped PLGA by a W/O/W double emulsion solvent evaporation method. The results of characterization demonstrated that the particle size of the PLGA microspheres were about 80–150 μm, the maximum loading capacity and encapsulation efficiency of BSA-loaded microspheres were 67.51 μg/(mg microspheres) and 78.39%, respectively, which were better than linear PLGA. The in vitro release profiles of BSA in phosphate buffer saline (PBS) lasted for 37 h. Drug release profiles can be affected by polymer molecular weight and the ratio of polymer to drug. The maximum release percentage was 80%.
    Polymer Bulletin 01/2012; · 1.33 Impact Factor
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    ABSTRACT: In this article, the pretreatment before extrusion between the PLA and the modified starch was researched. The research on the composites of PLA and the modified starch focused on improving its compatibility and mechanical properties. The pretreatment samples were characterized by solid 13C-NMR and the chemical titration of the carboxyl end (–COOH) groups in PLA. The results illuminated that the pretreatment reaction was successful and the –COOH in PLA had reacted with the –OH in modified starch. The compatibility of the composites was determined by differential scanning calorimetry and scanning electron microscopy. The results showed that pretreatment could improve the compatibility of the composites. The mechanical properties of the composites were also enhanced. This approach is identified as a reasonable method to produce commercial PLA/modified starch composites with economical feasibility.
    Polymer Bulletin 01/2012; 68(7). · 1.33 Impact Factor
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    ABSTRACT: A novel non-viral gene vector based on poly[poly(ethylene glycol) methacrylate] (PMPEG) and l-glutathione (GSH) grafted chitosan (CS) has been fabricated. First, well-defined brush-like PMPEG living polymers with dithioester residues were prepared by the reversible addition-fragmentation chain transfer (RAFT) polymerization and grafted onto the allylchitosan via radical coupling method. Then, the tripeptide GSH was introduced onto the end of PMPEG chain to give a CS-PMPEG-GSH conjugate. In comparison with pristine chitosan, CS-PMPEG-GSH conjugate could not only condense plasmid DNA (pDNA) and prevent the condensed CS-PMPEG-GSH/pDNA nanoparticle self-aggregation, but also increase the binding ability to cell membrane efficiently and improve decondensed ability of pDNA from the nanoparticles in cytoplasm which thus has resulted in the higher transfection efficiency in mouse embryonic fibroblast cells (NIH3T3). In addition, cytotoxicity assays showed that the conjugate is less cytotoxic than CS, and still retain the cationic polyelectrolyte characteristic as chitosan. These results indicate that the non-viral vector is a promising candidate for gene therapy in clinical application.
    Journal of Controlled Release 06/2011; 154(2):177-88. · 7.63 Impact Factor
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    ABSTRACT: Macroporous protein imprinted films (porous-MIP) have been fabricated on the surface of quartz crystal microbalance (QCM) using methyl methacrylate (MMA) as main monomer and trimethylolpropane trimethacrylate (TRIM) as a cross-linker. Macropores were generated by employing calcium carbonate nanoparticles as porogen. The imprinted special surface area and the quantity of the imprinted sites were increased by the formation of macropores on the films. Since the macropores were interconnected in structure, the mass transport and accessibility of protein to the active sites through the material were not affected. In comparison with the nonporous imprinted (nonporous-MIP) films, the porous-MIP films exhibited better affinity and selectivity to template, the binding capacity and mass sensitivity of the biosensor were enhanced. The rigid skeleton structure made the films durable in the recycled tests. The strategy proposed here is generally applicable for constructing high performance biosensor devices.
    Sensors and Actuators B-chemical - SENSOR ACTUATOR B-CHEM. 01/2011; 153(1):96-102.
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    ABSTRACT: P oly (lactic acid) (PLA) is one of the most promising biodegradable materials with excellent mechanical properties, but the disadvantages of stiffness, poor thermal stability, and high costs limit its applications in general use plastics such as industrial packaging and agriculture films. In present work, biodegradable PLA/starch composites are prepared from PLA and etherified starch (EST) by extrusion and uniax-ial orientation processing with a pretreated mixing procedure under a programmed tem-perature. The products are examined using Fourier transform infrared (FTIR) spec-troscopy technique. The results revealed that small amount of PLA molecules have strong interaction with EST which may be ascribed to the esterification between the terminal carboxyl groups of PLA and hydroxyl groups in EST. The morphological properties observed by scanning electron microscopy (SEM) technique confirmed that the composites with a pretreatment procedure had much better dispersion and homogeneity of starch in the PLA matrix than the composites without the pretreatment procedure. Consequently, an improvement in mechanical properties has been achieved. Comparing with the samples without the pretreatment procedure, the mechanical performances such as tensile strength, elongation-at-break and modulus of the composites with a pretreatment procedure were significantly improved. This approach is identified as a reasonable method to produce commercial PLA/starch com-posites with economical feasibility.