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1.
Poly( , -lactic acid) (PLA)-based particles, obtained by the emulsification–diffusion process, were surface-modified by electrostatic adsorption of poly(ethylenimine) (PEI). The amount of immobilized PEI and the conformation of the polycation at the interface were dependent on the ionic strength of the media. In the absence of salt, or at low ionic strength, the adsorbed amounts of PEI, the surface charge and the critical concentration for coagulation (CCC) of the modified particles were lower than when the adsorption was achieved at elevated ionic strength. Moreover, at low salt concentration, isotherms were of Langmuir type, suggesting the formation of monolayers. The differences in PEI surface conformation had consequences on the DNA binding capacity of the particles, on the plasmid DNA conformation at the interface and on the DNA release in various media. When PEI was adsorbed in a 50 mM phosphate buffer, the amount of bound plasmid and the strength of binding were higher than when PEI was adsorbed in water. From these differences in physico-chemical properties, one can expect differences in transfection or immunization performances of the vectors.  相似文献   

2.
壳聚糖修饰PLGA阳离子型纳米微球的制备与表征   总被引:6,自引:1,他引:6  
采用单乳化-溶剂(O/W)挥发技术制备表面带正电荷的壳聚糖(CHS)修饰聚乙/丙交酯(PLGA)纳米微球(PLGA/CHS), 通过正交试验优化了纳米微球的制备条件. 结果表明, 微球粒径可控制在150~200 nm内, 在pH=4时, 纳米微球表面电位最高为55 mV. 影响微球粒径的主要因素是聚合物的浓度, CHS的分子量和浓度以及介质的pH值对微球表面电位也有明显影响. 制备粒径较小而表面电位较高的PLGA/CHS纳米微球条件为: ρ(CHS)=3 mg/mL, ρ(PLGA)=10 mg/mL, Vo/Va=1/4. SEM图像显示经CHS修饰的PLGA的纳米微球形状规整, 荧光显微观察和XPS分析结果证实CHS包覆于微球表面.  相似文献   

3.
Poly(d,l-lactide) microspheres with progesterone loadings of 0, 10, 20, 30 and 50% w/w were manufactured using an interrupted solvent evaporation process. Spherical microspheres with loadings close to the theoretical values were produced. The glass transition of the polymer could be identified by a step change in the heat capacity measured by TMDSC. Progesterone was found to plasticise the glass transition temperature at contents of 20% w/w or less. At a 30% loading, cold crystallisation of progesterone was seen indicating that an amorphous form of the drug was present; these microspheres were found to exhibit a pitted surface. TMDSC of the 50% progesterone samples suggested that most of the drug was present as crystals. This was supported by the SEM and PXRD results. This revised version was published online in July 2006 with corrections to the Cover Date.  相似文献   

4.
The interaction of PEGylated poly(amino acid)s with their biological targets depends on their chemical nature and spatial arrangement of their building blocks. The synthesis, self‐assembly, and DNA complexation of ABC terblock copolymers consisting of poly(ethylene glycol), (PEG), poly(l ‐lysine), and poly(l ‐leucine), are reported. Block copolymers are produced by a metal‐free, living ring‐opening polymerization of respective amino acid N‐carboxyanhydrides using amino‐terminated PEG as macroinitiator: (PEG‐b‐p(l ‐Lys)xb‐p(l ‐Leu)y, PEG‐b‐p(l ‐Leu)xb‐p(l ‐Lys)y, and PEG‐b‐p((l ‐Lys)xco‐p(l ‐Leu)y). Sizes of self‐assembled nanoparticles depend on the formation method. The nanoprecipitation method proves useful for copolymers with the poly(l ‐lysine) block protected as trifluoroacetate, effective diameters range between 92 and 132 nm, while direct dissolution in distilled water is suitable for the deprotected copolymers, yielding effective diameters between 52 and 173 nm. Critical micelle concentration (CMC) analyses corroborate particle size analyses and show a distinct impact of the molecular architecture; the lowest CMC (8 µg mL−1) is observed when the poly(l ‐leucine) segment forms the C‐block and the hydrophilic, disassembly driving poly(l ‐lysine) segment is short. DNA complexation, evaluated by gel motility and RiboGreen analyses, depends strongly on the molecular architecture. A more efficient DNA complexation is observed when poly(l ‐lysine) and poly(l ‐leucine) form individual blocks as opposed to them forming a copolymer.  相似文献   

5.
We report an approach to the chemical oxidation of a ferrocene-containing cationic lipid [bis(11-ferrocenylundecyl)dimethylammonium bromide, BFDMA] that provides redox-based control over the delivery of DNA to cells. We demonstrate that BFDMA can be oxidized rapidly and quantitatively by treatment with Fe(III)sulfate. This chemical approach, while offering practical advantages compared to electrochemical methods used in past studies, was found to yield BFDMA/DNA lipoplexes that behave differently in the context of cell transfection from lipoplexes formed using electrochemically oxidized BFDMA. Specifically, while lipoplexes of the latter do not transfect cells efficiently, lipoplexes of chemically oxidized BFDMA promoted high levels of transgene expression (similar to levels promoted by reduced BFDMA). Characterization by SANS and cryo-TEM revealed lipoplexes of chemically and electrochemically oxidized BFDMA to both have amorphous nanostructures, but these lipoplexes differed significantly in size and zeta potential. Our results suggest that differences in zeta potential arise from the presence of residual Fe2+ and Fe3+ ions in samples of chemically oxidized BFDMA. Addition of the iron chelating agent EDTA to solutions of chemically oxidized BFDMA produced samples functionally similar to electrochemically oxidized BFDMA. These EDTA-treated samples could also be chemically reduced by treatment with ascorbic acid to produce samples of reduced BFDMA that do promote transfection. Our results demonstrate that entirely chemical approaches to oxidation and reduction can be used to achieve redox-based ‘on/off’ control of cell transfection similar to that achieved using electrochemical methods.  相似文献   

6.
Amphiphilic triblock copolymers, poly(ethyl cyanoacrylate)‐b‐poly(ethylene glycol)‐b‐poly(ethyl cyanoacrylate) (PECA‐b‐PEG‐b‐PECA), were synthesized via oxyanion‐initiated polymerization with sodium alcoholate‐terminated PEG as macroinitiator. PECA‐b‐PEG‐b‐PECA were characterized by gel permeation chromatography system, 1H NMR and FTIR. The results indicate that the copolymerization is well controlled with narrow molecular weight distribution. The dexamethasone (DXM)‐loaded PECA‐b‐PEG‐b‐PECA nanoparticles (NPs) were prepared by nanoprecipitation technique and then characterized by Laser Particle Size Analyzer, 1H NMR and transmission electron microscopy. The drug‐loaded PECA‐b‐PEG‐b‐PECA NPs are of spherical shape with average size of less than 100 nm. The drug‐loaded amount (DLA) and encapsulation efficiency of DLNPs were investigated by HPLC. The results show that DXM can be effectively incorporated into PECA‐b‐PEG‐b‐PECA NPs, which provides an optional delivery system for DXM and other hydrophobic drugs. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 7809–7815, 2008  相似文献   

7.
Summary: The aims of the present work were to prepare and characterize nanocapsules containing antitumoral agent methotrexate (MTX) from poly(D ,L -lactide) (PLA) and poly(D ,L -lactide)-poly(ethylene glycol) diblock copolymer (PLA-PEG) with the purpose of administrating this drug by topical ocular route for primary ocular lymphoma treatment. Nanocapsules were prepared by the interfacial deposition of preformed polymer. The influences of the initial amount of MTX on the encapsulation efficiency, drug recovery and drug content, as well as the physicochemical properties of the particles were evaluated. The particle mean diameters were 246 and 146 nm, and zeta potential values were −38.8 and −33.6 mV, for the MTX-loaded nanocapsules prepared from PLA and PLA-PEG, respectively. The methotrexate content in the particles increased with the increasing in the drug amount added to the formulations, but the drug recovery decreased significantly. After 4 h of in vitro release, 28 and 86% of MTX was released from PLA and PLA-PEG nanocapsules, respectively.  相似文献   

8.
A versatile family of cationic methacrylate copolymers containing varying amounts of primary and tertiary amino side groups were synthesized and investigated for in vitro gene transfection. Two different types of methacrylate copolymers, poly(2‐(dimethylamino)ethyl methacrylate)/aminoethyl methacrylate [P(DMAEMA/AEMA)] and poly(2‐(dimethylamino)ethyl methacrylate)/aminohexyl methacrylate [P(DMAEMA/AHMA)], were obtained by reversible addition‐fragmentation chain transfer (RAFT) copolymerization of dimethylaminoethyl methacrylate (DMAEMA) with N‐(tert‐butoxycarbonyl)aminoethyl methacrylate (Boc‐AEMA) or N‐(tert‐butoxycarbonyl)aminohexyl methacrylate (Boc‐AHMA) followed by acid deprotection. Gel permeation chromatography (GPC) measurements revealed that Boc‐protected methacrylate copolymers had Mn in the range of 16.1–23.0 kDa and low polydispersities of 1.12–1.26. The copolymer compositions were well controlled by monomer feed ratios. Dynamic light scattering and agarose gel electrophoresis measurements demonstrated that these PDMAEMA copolymers had better DNA condensation than PDMAEMA homopolymer. The polyplexes of these copolymers revealed low cytotoxicity at an N/P ratio of 3/1. The in vitro transfection in COS‐7 cells in serum free medium demonstrated significantly enhanced (up to 24‐fold) transfection efficiencies of PDMAEMA copolymer polyplexes as compared with PDMAEMA control. In the presence of 10% serum, P(DMAEMA/AEMA) and P(DMAEMA/AHMA) displayed a high transfection activity comparable with or better than 25 kDa PEI. These results suggest that cationic methacrylate copolymers are highly promising for development of safe and efficient nonviral gene transfer agents. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 2869–2877, 2010  相似文献   

9.
Biodegradable and amphiphilic triblock copolymers poly(ethyl ethylene phosphate)-poly(3-hydroxy-butyrate)-poly(ethyl ethylene phosphate) (PEEP-b-PHB-b-PEEP) have been successfully synthesized through ring-opening polymerization. The structures are confirmed by gel permeation chromatography and NMR analyses. Crystallization investigated by X-ray diffraction reveals that the block copolymer with higher content of poly(ethyl ethylene phosphate) (PEEP) is more amorphous, showing decreased crystallizability. The obtained copolymers self-assemble into biodegradable nanoparticles with a core-shell micellar structure in aqueous solution, verified by the probe-based fluorescence measurements and transmission electronic microscopy (TEM) observation. The hydrophobic poly(3-hydroxybutyrate) (PHB) block serves as the core of the micelles and the micelles are stabilized by the hydrophilic PEEP block. The size and size distribution are related to the compositions of the copolymers. Paclitaxel (PTX) has been encapsulated into the micelles as a model drug and a sustained drug release from the micelles is observed. MTT assay also demonstrates that the block copolymers are biocompatible, rendering these copolymers attractive for drug delivery. Supported by the Specialized Research Fund for the Doctoral Program of Higher Education of China (Grant No.20060358036)  相似文献   

10.
Three new mononuclear cobalt(II) complexes containing ligands with extended planar quinoxaline moieties, {dipyrido[3,2‐a:2′,3′‐c]phenazine (dppz) or dipyrido[3,2‐d:2′,3′‐f]quinoxaline (dpq)}, viz. [Co(dppz)(acac)2] · CH3OH ( 1 ), [Co(dpq)(tfnb)2] ( 2 ) and [Co(dpq)(dbm)2] ( 3 ), where acac = acetylacetonate, tfnb = benzoyltrifluoroacetone and dbm = dibenzoylmethane, have been synthesized and structurally characterized as octahedral complexes. The binding ability of the complexes with calf thymus (CT)‐DNA has been investigated by spectroscopic and viscosity measurements. Results indicate that all complexes bind to CT‐DNA via intercalative mode, and the DNA binding affinity of dppz complex 1 is apparently stronger than that of dpq complexes 2 and 3 . Furthermore, DNA photocleavage experiments indicate that these complexes are efficient DNA cleaving agents in UV‐A (365 nm) and hydroxyl radical (HO·), singlet oxygen (1O2) and superoxide anion (1O2?) serve as the major cleavage active species. In addition, interaction of the complexes with bovine serum albumin (BSA) was investigated using UV ? visible and fluorescence methods, which indicated that all complexes could quench the intrinsic fluorescence of BSA in a static quenching process. Copyright © 2014 John Wiley & Sons, Ltd.  相似文献   

11.
《先进技术聚合物》2018,29(6):1706-1717
Biodegradable poly(lactic acid) (PLA)/poly(butylene adipate‐co‐terephthalate) (PBAT) blends and films were prepared using melt blending and blowing films technique in the presence of chain extender‐Joncryl ADR 4370F. The ADR contains epoxy functional groups and used as a compatibilizer. The morphological, mechanical, rheological, thermal, and crystalline properties of the PLA/PBAT/ADR blown films were studied. Scanning electron microscopy micrographs of the films revealed more ductile deformation with increasing PBAT content. The addition of PBAT enhanced the toughness of the PLA film. Tensile tests indicated that the elongation at break increased from 20.5% to 334.6% in the machine direction and from 7.1% to 715.9% in the transverse direction. The Young modulus increased from 2690.5 to 395.6 MPa in the machine direction and from 2623.5 to 154.0 MPa in the transverse direction. The sealing strength of 40/60/0.15 PLA/PBAT/ADR film was the highest among all the samples up to 9.4 N 15 mm−1. These findings gave important implications for designing and manufacturing polymer packaging materials.  相似文献   

12.
A poly(D,L ‐lactide)–bromine macroinitiator was synthesized for use in the preparation of a novel biocompatible polymer. This amphiphilic diblock copolymer consisted of biodegradable poly(D,L ‐lactide) and 2‐methacryloyloxyethyl phosphorylcholine and was formed by atom transfer radical polymerization. Polymeric nanoparticles were prepared by a dialysis process in a select solvent. The shape and structure of the polymeric nanoparticles were determined by 1H NMR, atomic force microscopy, and ζ‐potential measurements. The results of cytotoxicity tests showed the good cytocompatibility of the lipid‐like diblock copolymer poly(2‐methacryloyloxyethyl phosphorylcholine)‐block‐poly(D,L ‐lactide). © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 688–698, 2007  相似文献   

13.
The synthesis of poly(2‐ethyl‐2‐oxazoline)‐b‐linear poly(ethylenimine) (PEtOx‐b‐LPEI) copolymers by selective basic hydrolysis of PEtOx‐b‐poly(2‐H‐2‐oxazoline) (PEtOx‐b‐PHOx) is described. For this purpose, an easy method for the preparation of the 2‐H‐2‐oxazoline (HOx) monomer was developed. Based on the microwave‐assisted polymerization kinetics for this monomer, PEtOx‐b‐PHOx copolymers were prepared. Subsequently, the block copolymers were selectively hydrolyzed to PEtOx‐b‐LPEI under basic conditions. The success of the polymerizations and subsequent post‐polymerization reactions was demonstrated by 1H NMR spectroscopy and MALDI‐TOF‐MS investigations of the obtained polymers. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012  相似文献   

14.
Tseng WL  Huang MF  Huang YF  Chang HT 《Electrophoresis》2005,26(16):3069-3075
We report the analysis of long DNA molecules by nanoparticle-filled capillary electrophoresis (NFCE) under the influences of hydrodynamic and electrokinetic forces. The gold nanoparticle (GNP)/polymer composites (GNPPs) prepared from GNPs and poly(ethylene oxide) were filled in a capillary to act as separation matrices for DNA separation. The separations of lambda-DNA (0.12-23.1 kbp) and high-molecular-weight DNA markers (8.27-48.5 kbp) by NFCE, under an electric field of -140 V/cm and a hydrodynamic flow velocity of 554 microm/s, were accomplished within 5 min. To further investigate the separation mechanism, the migration of lambda-DNA was monitored in real time using a charge-coupled device (CCD) imaging system. The GNPPs provide greater retardation than do conventional polymer media when they are encountered during the electrophoretic process. The presence of interactions between the GNPPs and the DNA molecules is further supported by the fluorescence quenching of prelabeled lambda-DNA, which occurs through an energy transfer mechanism. Based on the results presented in this study, we suggest that the electric field, hydrodynamic flow, and GNPP concentration are the three main determinants of DNA separation in NFCE.  相似文献   

15.
The hydrolytic erosion of poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (PLGA-NPs) was investigated in vitro. The changes in physical properties of the nanoparticles with time were evaluated by ultra high-pressure liquid chromatographic (UHPLC) analysis, particle size analysis and scanning electron microscopy (SEM). Mass reduction data demonstrated a triphasic erosion pattern for PLGA-NPs with nearly no mass loss (3.0%) up to a week, followed by a rapid mass loss (weeks 1-3, 61.4%), and further followed by slow mass loss (weeks 3-5, 19.8%). SEM revealed microcavitation on the surface of nanoparticles, which tended to increase with the erosion time and eventually particle fragmentation was evident at 5 weeks. A significant increase in particle size was observed at 4 weeks which can be attributed to particle aggregation, however, at about 5 weeks, the particle size decreased significantly owing to particle fragmentation. The hydrolytic erosion of PLGA-NPs was found to be specifically proton catalyzed. The release profile of the model drug, moxifloxacin, from PLGA-NPs was closely related to nanoparticle erosion except for the initial burst release which was based on diffusion. The presence of chitosan in the PLGA-NPs accelerated the rate of erosion of the nanoparticles and reduced the burst release of the drug. An understanding of the erosion mechanism and alteration in erosion by chitosan could give desirable and more uniform drug release kinetics from PLGA-NPs.  相似文献   

16.
The crystallization and melting behaviors of poly (vinylidene fluoride) (PVDF) with small amount of nanoparticles (1 wt %), such as montmorillonite (MMT), SiO2, CaCO3, or polytetrafluoroethylene (PTFE), directly prepared by melt‐mixing method were investigated by scanning electron microscopy (SEM), polarizing optical microscopy, Fourier transform infrared spectroscopy, wide angle X‐ray diffraction (WAXD), and differential scanning calorimetry (DSC). The nanoparticle structure and the interactions between PVDF molecule and nanoparticle surface predominated the crystallization behavior and morphology of the PVDF. Small amount addition of these four types of nanoparticles would not affect the original crystalline phase obtained in the neat PVDF sample (α phase), but accelerated the crystallization rate because of the nucleation effect. In these four blend systems, MMT or PTFE nanoparticles could be well applied for PVDF nanocomposite preparation because of stronger interactions between particle surface and PVDF molecules. The nucleation enhancement and the growth rate of the spherulites were decreased in the order SiO2 > CaCO3 > PTFE > MMT. The melting and recrystallization of PVDF was found in MMT addition sample, because of the special ways of ordering of the PVDF chains. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2010  相似文献   

17.
PMLA nanoparticles with diameters of 150-250 nm are prepared, and their hydrolytic degradation is studied under physiological conditions. Degradation occurs by hydrolysis of the side chain methyl ester followed by cleavage of the main-chain ester group with methanol and L-malic acid as the final degradation products. No alteration of the cell viability is found after 1 h of incubation, but toxicity increases significantly after 3 d, probably due to the noxious effect of the released methanol. Anticancer drugs temozolomide and doxorubicin are encapsulated in the NPs with 20-40% efficiency, and their release is monitored using in vitro essays. Temozolomide is fully liberated within several hours, whereas doxorubicin is steadily released from the particles over a period of 1 month.  相似文献   

18.
由聚N,N-二乙基胺基甲基丙烯酸乙酯(PDEAEMA)与铁纳米颗粒复合制得的纳米铁基复合材料。纳米铁微球表面钝化形成Fe3O4后,将多巴胺基引发剂修饰在Fe3O4的表面,通过表面引发原子转移自由基聚合(SI-ATRP)将DEAEMA单体聚合在修饰了多巴胺基引发剂的表面获得Fe-g-PDEAEMA复合微球。显微结果表明修饰PDEAEMA后,复合微球的分散性得到了一定的提高;XRD数据表明在纳米铁表面生成了一层Fe3O4壳。利用透光率测定研究了复合微球的p H敏感性,表明在酸性条件下悬浮性良好,在碱性条件下发生了沉降,复合微球具有p H敏感性。通过还原降解酸性大红染料,表明Fe-g-PDEAEM复合微球与纳米铁相比,其还原性有所提高,合成的Fe-g-PDEAEMA复合微球可用于氯代烃等氯化物污染的水体保护。  相似文献   

19.
Reaction of 1-(2′-pyridylazo)-2-naphthol (Hpan) with [Ru(dmso)4Cl2] (dmso = dimethylsulfoxide), [Ru(trpy)Cl3] (trpy = 2,2′,2″-terpyridine), [Ru(bpy)Cl3] (bpy = 2,2′-bipyridine) and [Ru(PPh3)3Cl2] in refluxing ethanol in the presence of a base (NEt3) affords, respectively, the [Ru(pan)2], [Ru(trpy)(pan)]+ (isolated as perchlorate salt), [Ru(bpy)(pan)Cl] and [Ru(PPh3)2(pan)Cl] complexes. Structures of these four complexes have been determined by X-ray crystallography. In each of these complexes, the pan ligand is coordinated to the metal center as a monoanionic tridentate N,N,O-donor. Reaction of the [Ru(bpy)(pan)Cl] complex with pyridine (py) and 4-picoline (pic) in the presence of silver ion has yielded the [Ru(bpy)(pan)(py)]+ and [Ru(bpy)(pan)(pic)]+ complexes (isolated as perchlorate salts), respectively. All the complexes are diamagnetic (low-spin d6, S = 0) and show characteristic 1H NMR signals and intense MLCT transitions in the visible region. Cyclic voltammetry on all the complexes shows a Ru(II)–Ru(III) oxidation on the positive side of SCE. Except in the [Ru(pan)2] complex, a second oxidative response has been observed in the other five complexes. Reductions of the coordinated ligands have also been observed on the negative side of SCE. The [Ru(trpy)(pan)]ClO4, [Ru(bpy)(pan)(py)]ClO4 and [Ru(bpy)(pan)(pic)]ClO4 complexes have been observed to bind to DNA, but they have not been able to cleave super-coiled DNA on UV irradiation.  相似文献   

20.
A straightforward coassembly strategy was developed for the preparation of polymeric nanoparticles driving by the intermolecular hydrogen bond between neutral poly(2-methyl-2-oxaozline)(PMeOx),tannic acid(TA) and doxorubicin hydrochloride(Dox).The occurrence of the hydrogen-bonding amongst the different functionalities within the formed nanoparticles was verified by infrared(IR) spectroscopy.Scanning electron microscopy(SEM),dynamic light scattering(DLS),UV-vis absorption and photoluminescent measurements indicated the rapid formation of uniform and water dispersible/stable nanoparticles.The relative poor stability of PMeOx-TA-Dox in fetal bovine serum(FBS) solution enabled the rapid separation of Dox and PMeOx-TA,facilitating the release of Dox and its entrance into cellular nuclei as revealed by confocal laser scanning microscopy(CLSM).The presented strategy may provide an efficient alternative for the construction of multifunctional nanomedicines.  相似文献   

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