A fully biocompatible poly(ethylene glycol)–gold plasmonic crystal for optical sensing

A significant challenge in nano and biophotonics is to demonstrate fully biocompatible nano-optics devices that can perform biofunctions in vivo. Here we present a scalable, cost-effective, and large-area nanofabrication method for creating a quasi-3D plasmonic crystal using poly(ethylene glycol) (PEG) and gold (Au), both biocompatible materials. The plasmonic crystal was prepared by depositing an Au layer on the upper hemisphere of the replicated PEG nanospheres array. Additionally we demonstrated that the fabricated plasmonic crystal can behave as a label-free glucose sensor with sensitivity and figure-of-merit values comparable to other plasmonic crystal based sensors.     

Tissue engineering scaffolds of mesoporous magnesium silicate and poly(ε-caprolactone)–poly(ethylene glycol)–poly(ε-caprolactone) composite

Mesoporous magnesium silicate (m-MS) and poly(ε-caprolactone)–poly(ethylene glycol)–poly(ε-caprolactone) (PCL–PEG–PCL) composite scaffolds were fabricated by solvent-casting and particulate leaching method. The results suggested that the incorporation of m-MS into PCL–PEG–PCL could significantly improve the water adsorption of the m-MS/PCL–PEG–PCL composite (m-MPC) scaffolds. The in vitro degradation behavior of m-MPC scaffolds were determined by testing weight loss of the scaffolds after soaking into phosphate buffered saline (PBS), and the result showed that the degradation of m-MPC scaffolds was obviously enhanced by addition of m-MS into PCL–PEG–PCL after soaking for 10 weeks. Proliferation of MG63 cells on m-MPC was significantly higher than MPC scaffolds at 4 and 7 days. ALP activity on the m-MPC was obviously higher than MPC scaffolds at 7 days, revealing that m-MPC could promote cell differentiation. Histological evaluation showed that the introduction of m-MS into PCL–PEG–PCL enhanced the efficiency of new bone formation when the m-MPC scaffolds implanted into bone defect of rabbits. The results suggested that the inorganic/organic composite of m-MS and PCL–PEG–PCL scaffolds exhibited good biocompatibility, degradability and osteogenesis.     

Microencapsulation of cytarabine using poly(ethylene glycol)–poly(ε-caprolactone) diblock copolymers as surfactant agents

Background: The high water solubility and the low molecular weight of cytarabine (Ara-C) are major obstacles against its particulate formulation as a result of its low affinity to the commonly used hydrophobic polymers. Methods: Biodegradable cytarabine loaded-microparticles (Ara-C MPs) were elaborated using poly(?-caprolactone) (PCL) and monomethoxy polyethylene glycol (mPEG)–PCL diblock copolymer in order to increase the hydrophilicity of the polymeric matrix. For this purpose, a series of mPEG–PCL diblock copolymers with different PCL block lengths were synthesized. Compositions and molecular weights of obtained copolymers were characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance, size exclusion chromatography, and size exclusion chromatography–multi-angle laser light scattering. Ara-C MPs were prepared by double emulsion-solvent evaporation method. The effects of varying PCL block lengths on microparticle encapsulation efficiency, size, and zeta potential were evaluated. Results: Increasing the PCL block lengths of copolymers substantially increased the Ara-C encapsulation efficiency and the microparticle size but it decreased their zeta potential. Microparticles were spherical in shape, with a smooth surface and composed of homogenously distributed Ara-C-containing aqueous domains in the polymer matrix. The in vitro drug release kinetics of the optimized microparticles showed a hyperbolic profile with an initial burst release. Conclusion: These results showed the important role of the amphiphilic diblock copolymers as stabilizing agent in the encapsulation of Ara-C in PCL microparticles, suggesting their potential use for the microparticulate formulations of other small hydrophilic bioactive molecules.     

Ocular Permeability of Pirenzepine Hydrochloride Enhanced by Methoxy poly(ethylene glycol)–poly(D,L-lactide) Block Copolymer

Methoxy poly(ethylene glycol)–poly(D,L-lactide) block copolymer was tested as an ocular permeation enhancer for pirenzepine hydrochloride. The block copolymers with the methoxy poly(ethylene glycol) to poly(D,L-lactide) weight ratio of 80/20, 50/50, 40/60 were synthesized by a ring-opening polymerization procedure. In vitro transcorneal experiments demonstrated that the block copolymer 80/20 significantly enhanced the transcorneal permeation of pirenzepine at the mass ratio of 1/1.4 (pirenzepine hydrochloride/copolymer). Interaction between pirenzepine and copolymer was identified by infrared spectroscopy analysis and dialysis experiments. Ocular pharmacokinetics of pirenzepine/copolymer preparation by in vivo instillation experiments confirmed that block copolymer could enhance the ocular penetration of pirenzepine. Ocular chronic toxicity experiments of block copolymer and pirenzepine/copolymer preparation were studied on rabbits, and no significant toxicity in both groups was observed within 9 months. It could conclude that pirenzepine/copolymer preparation is effective and safe in ocular delivery of pirenzepine.     

Optimization of the lyophilization process for long-term stability of solid–lipid nanoparticles

Objectives: To optimize a lyophilization protocol for solid–lipid nanoparticles (SLNs) loaded with dexamethasone palmitate (Dex-P) and to compare the long-term stability of lyophilized SLNs and aqueous SLN suspensions at two storage conditions.

Materials and Methods: The effect of various parameters of the lyophilization process on SLN redispersibility was evaluated. A three month stability study was conducted to compare changes in the particle size and drug loading of lyophilized SLNs with SLNs stored as aqueous suspensions at either 4°C or 25°C/60% relative humidity (RH).

Results and Discussion: Of nine possible lyoprotectants tested, sucrose was shown to be the most efficient at achieving SLN redispersibility. Higher freezing temperatures, slower freezing rates, and longer secondary drying times were also shown to be beneficial. Loading of the SLNs with Dex-P led to slightly larger particle size and polydispersity index increases, but both parameters remained within an acceptable range. Drug loading and particle shape were maintained following lyophilization, and no large aggregates were detected. During the stability study, significant growth and drug loss were observed for aqueous SLN suspensions stored at 25°C/60% RH. In comparison, lyophilized SLNs stored at 4°C exhibited a consistent particle size and showed <20% drug loss. Other storage conditions led to intermediate results.

Conclusions: A lyophilization protocol was developed that allowed SLNs to be reconstituted with minimal changes in their physicochemical properties. During a three month period, lyophilized SLNs stored at 4°C exhibited the greatest stability, showing no change in the particle size and a minimal reduction in drug retention.     

Preparation and properties of polyrotaxane from α-cyclodextrin and poly(ethylene glycol) with poly(vinyl alcohol)

α–Cyclodextrin (α-CD) was found to form inclusion complexes with poly(ethylene glycol) (PEG) having a crystalline state in high yields, which have been investigated extensively in the past. Formation of an inclusion complex depends strongly on structure, molecular weight and geometry of the polymer. Development of a dicomponent inclusion complex (DIC) of PEG and α-CD in the presence of poly(vinyl alcohol) (PVA) and initiation of hexagonal crystals upon sonication have exhibited various microstructures. Formation of the new inclusion complex in PVA heavily depends on the concentration of PVA, temperature and sonication time. The complexes produced are characterized by FTIR, HNMR spectra and powder X-ray. ¹HNMR of the complexes demonstrate that their stoichiometric ratio is 2:1 (two ethylene glycol units and one α-CD). X-ray patterns of PEG–α-CD complex indicate that the α-CD forms channels whereas PEG/α-CD/PVA creates cage-type structures.     

Synthesis and properties of poly(ethylene glycol) macromer/β-chitosan hydrogels

Semi-interpenetrating polymer network (semi-IPN) hydrogels composed of -chitosan and poly(ethylene glycol) diacrylate macromer (PEGM) were synthesized and characterized for the application as potential biomedical materials. The mixture of PEGM and -chitosan, dissolved in water including a small amount of acetic acid, was cast to prepare hydrogel films, followed by a subsequent crosslinking with 2,2-dimethoxy-2-phenylacetophenone as a non-toxic photoinitiator by ultraviolet irradiation. Photocrosslinked hydrogels exhibited relatively high equilibrium water content in the range 77–83% which is mainly attributed to the free water content rather than to the bound water, hydrogen bonded with components in semi-IPN hydrogels. The crystallinity, thermal properties and mechanical properties of semi-IPN hydrogels were studied. All the photocrosslinked hydrogels revealed a remarkable decrease in crystallinity. The glass transition temperatures, Tg, of crosslinked PEGM segment in semi-IPNs increased compared with poly(ethylene glycol) itself. However, with increasing -chitosan content their Tg decreased owing to the higher degree of crosslinking. The tensile strengths of semi-IPNs in dry state were rather high, but those of hydrogels in wet state decreased drastically.     

Particle formation and aggregation–collapse behavior of poly(N-isopropylacrylamide) and poly(ethylene glycol) block copolymers in the presence of cross-linking agent

The effect of feed molar ratio of N-isopropylacrylamide (NIPAM) to poly(ethylene oxide) (PEO) on the particle formation of poly(N-isopropylacrylamide) (PNIPAM) and PEO block copolymers (PNIPAM-b-PEO) and their aggregation-collapse behavior have been studied in aqueous solutions. It is found that in the presence of cross-linking agent N,N'-methylenebisacryla-mide (BIS), different morphologies of PNIPAM-b-PEO copolymers can be obtained, including a grafting-like structure, a hemispherical core-shell structure and a well-defined core-shell nanoparticle, as the feed molar amount of NIPAM in the copolymerization is increased. The increase in temperature causes the self-aggregation of grafting-like copolymers and hemispherical particles due to the hydrophobic interaction between locally unshielded PNIPAM blocks prior to the conformational transition of PNIPAM. When the feed molar ratio of NIPAM to PEO exceeds a certain value, a well-defined core-shell nanoparticle can be produced during the copolymerization. At low concentrations, PNIPAM cores of single core-shell nanoparticles can undergo the conformational transition without aggregation. The increase in the concentration of the well-defined core-shell nanoparticles, however, results in a week aggregation at temperatures lower than the theta-temperature of pure PNIPAM due to the association of methyl groups at the periphery of PEO shells.     

Superior toughness obtained via tuning the compatibility of poly(ethylene terephthalate)/poly(ethylene–octene) blends

As a partial of the systematic investigation of the preparation and characterization of poly(ethylene terephthalate) (PET) blending/compounding materials with excellent comprehensive mechanics in the authors’ group, this study deals with the compatibilization modification of PET/elastomer blends to obtain superior toughness. Poly(ethylene–octene) (POE) was employed as elastomer toughener, while maleic anhydride grafted POE (mPOE) was selected as compatibilizer. To highlight the effect of compatibility on toughening, the sum amount of elastomer component, POE and mPOE, was fixed at 20 wt%, but the mass ratio of mPOE/POE was changeable. It is interesting to find that an optimization of toughening can be attained at 3 wt% mPOE, at which the notched impact strength is about 15 folds for that of neat PET. The toughening behavior observed is due to a combination of good dispersion of elastomer phase particles and, particularly, appropriate interfacial adhesion condition. Microscopic fractured morphology reveals that a moderate level of interfacial adhesion is important for good dispersion of elastomer phase and debonding between PET matrix and elastomer particles, which initiate matrix shear yielding to dissipate more energy than other interfacial adhesion conditions.     

Thermal behaviour of poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) tri-block copolymers

Thermal behavior of poly(-caprolactone)-poly(ethylene glycol)-poly(-caprolactone) tri-block copolymers with different block lengths is examined. Thermal behavior of specimens crystallized under the isothermal and dynamic condition are characterized by DSC. Also WAXD and SAXS are employed to investigate the structure. Depending on the relative length of each block, tri-block copolymers can be classified into three groups: PCL dominant crystallization; PEG dominant crystallization; and the competing case. When the crystallization of PEG and PCL are competing, the crystallization of each block shows strong dependency on the thermal hystory of crystallization, leading to multiple melting and crystallization peaks. Also, the typical micro-phase separation of block copolymers seems to play an important role, competing with crystallization, especially under the dynamic crystallization condition.     

Preparation and characterization of magnetic poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) microspheres

In this article, nano-magnetite particles (ferrofluid, Fe₃O₄) were prepared by chemical co-deposition method. A series of biodegradable triblock poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL, PCEC) copolymers were synthesized by ring-opening polymerization method from ε-caprolactone (ε-CL) initiated by poly(ethylene glycol) diol (PEG) using stannous octoate as catalyst. And the magnetic PCEC composite microspheres were prepared by solvent diffusion method. The properties of the ferrofluid, PCEC copolymer, and magnetic PCEC microspheres were studied in detail by SEM, VSM, XRD, Malvern Laser Particle Sizer, ¹H-NMR, GPC, and TG/DTG. Effects of macromolecular weight and concentration of polymer, and the time for ultrasound dispersion on properties of magnetic microspheres were also investigated. The obtained magnetic PCEC microspheres might have great potential application in targeted drug delivery system or cell separation. This work was financially supported by Chinese Key Basic Research Program (2004CB518800 and 2004CB518807), and Sichuan Key Project of Science and Technology (06(05SG022-021-02)). Qian ZY and Wang H did the even work with Gou ML, and are the co-first authors for this paper.     

Synthesis of poly(ethylene glycol) functionalized MWNTs and their inclusion complexes with α-cyclodextrin

Poly(ethylene glycol) (PEG) functionalized multiwalled carbon nanotubes (MWNTs), prepared by coupling of isocyanate-decorated MWNTs with PEG of different molecular weights (M _n = 400, 1000, 2000, and 4000 g/mol), were used to form inclusion complexes (ICs) with α-cyclodextrin (α-CD) through the grafted PEG chains being threaded with α-CD rings in aqueous solution. The FTIR, TGA, UV-Vis, and scanning electron microscopy (SEM) techniques were employed to characterize the formed ICs. The ICs formation time was monitored by UV-Vis spectroscopy, and the results indicated that the inclusion interaction between MWNT surface anchored PEG chains and α-CD was dependent on the molecular weight of PEG. The grafted PEG with molecular weights of 4000 and 2000 g/mol, respectively, can form ICs with α-CD, while the grafted PEG with molecular weights of 1000 and 400 g/mol, respectively, are difficult to form ICs with α-CD due to the steric hindrance from nanotubes. The stoichiometry value determined by TGA indicated that the ratio of ethylene glycol (EG) unit to α-CD in the resulted ICs was about 15:1. In addition, the morphology of the ICs was observed by SEM and transmission electron microscopy (TEM).     

Poly(acrylonitrile-co-itaconic acid)–poly(3,4-ethylenedioxythiophene) and poly(3-methoxythiophene) nanoparticles and nanofibres

This work aimed to produce poly(acrylonitrile-co-itaconic acid) (P(AN-co-IA)) nanocomposites with poly(3,4-ethylenedioxythiophene) (PEDOT) and poly(3-methoxythiophene) (PMOT). An anionic surfactant sodium dodecyl benzene sulphonate was used in emulsion polymerization for nanocomposite production. Incorporations of PEDOT and PMOT on the nanoparticles were characterized by scanning electron microscopy (SEM), atomic force microscopy, Fourier transform infrared-attenuated total reflectance spectroscopy and ultra-violet spectroscopy. These nanoparticles were blended with PAN and the blends were electrospun to produce P(AN-co-IA)–polythiophene-derivative-based nanofibres, and the obtained nanofibres were characterized by SEM and energy dispersive spectroscopy. In addition, electrochemical impedance studies conducted on nanofibres showed that PEDOT and PMOT in matrix polymer P(AN-co-IA) exhibited capacitive behaviour comparable to that of ITO–PET. Their capacitive behaviour changed with the amount of electroactive polymer.     

Interpenetrating polymer networks (IPN) based on gelatin/poly(ethylene glycol) dimethacrylate/clay nanocomposites: Structure–properties relationship

The effects of cross-linking sequence (simultaneous or sequential) and incorporation of exfoliated sodium-montmorillonite (Na⁺-MMT) nanoclay on the structure and properties of interpenetrating polymer networks (IPNs) based on gelatin/poly(ethylene glycol)dimethacrylate were studied by means of different complementary techniques. Gelatin and PEGdmA phases were cross-linked via chemical and in-situ UV curing, respectively. 2,2-dimethoxy-2-phenylacetophenone (DMPA) (1.5% w/w) was used as photo-initiator to cross-link PEGdmA. The results showed that the incorporation of small amount of Na⁺-MMT nanoplatelets accelerates the kinetics of chemical cross-linking of gelatin by glutaraldehyde (1.0% w/w). This led to a new hypothesis concerning the tuning structural evolution of the IPNs by the Na⁺-MMT content. In the case of simultaneous IPNs, in which both phases cross-linked at the same time, the accelerated cross-linking of gelatin in the presence of exfoliated sodium-montmorillonite led to increased structural homogeneity, improved mechanical and thermal properties. Incorporation of nanoclay did not show any significant effect on the structure and properties of the IPNs synthesized via sequential method in which gelatin and PEGdma phases were cross-linked separately. For the semi-IPNs, however, Na⁺-MMT induced macroscopic phase separation and resulted in lower mechanical properties. These results might shed light on the mechanisms underlying structure–property relationship in biohybrid IPNs based on gelatin as promising candidates for tissue engineering and drug delivery applications.     

Encapsulation and controlled release of lysozyme from electrospun poly(ε-caprolactone)/poly(ethylene glycol) non-woven membranes by formation of lysozyme–oleate complexes

In this study, the concept of hydrophobic ion pairing was adopted for incorporating lysozyme into electrospun poly(ε-caprolactone) (PCL)/poly(ethylene glycol) (PEG) non-woven membranes. The solubility of lysozyme in organic solvent was enhanced through the formation of lysozyme–oleate complexes, which could be directly loaded into PCL/PEG membranes using electrospinning technique. The resultant PCL/PEG nanofibers have a compact structure with an average diameter ranged from about 0.4 μm to 0.9 μm. The addition of PEG into the PCL nanofibers not only improved the hydrophilicity of the membrane, but also played an important role on in vitro lysozyme release rate. It was found that the release rate of lysozyme was enhanced with the increase of PEG content. In addition, the increase of salt concentration in the release medium accelerated lysozyme release. It has also been shown that the released lysozyme retained most of its enzymatic activity.     

Two novel calixarene functionalized iron oxide magnetite nanoparticles as a platform for magnetic separation in the liquid–liquid/solid–liquid extraction of oxyanions

This article focuses on the syntheses of 25,27-bis[3-(N-ethylsulfonic acid)aminopropxy]-26,28-dihydroxy-5,11,17,23-tetra-tert-butyl-calix[4]arene (3) and 25,27-bis[3-(N-ethyl-dihydrogen phosphate)aminopropxy]-26,28-dihydroxy-5,11,17,23-tetra-tert-butyl-calix[4]arene (4) as well as their immobilization onto [3-(2,3-epoxypropoxy)-propyl]-trimethoxysilane-modified Fe₃O₄ magnetite nanoparticles, and the extraction abilities of four new extractants which were characterized by a combination of FTIR, ¹H NMR, elemental analyses, transmission electron microscopy (TEM) and thermogravimetric analyses (TGA) involving electrostatic and hydrogen bonding interactions between the calixarene and oxide anions such as arsenate and dichromate anions. The extraction results indicate that these new calixarene derivatives having high extraction capabilities would be used as effective extractants for the removal of the dichromate/arsenate ions from water.     

Composition-dependent physical properties of poly[(vinylidene fluoride)-co-trifluoroethylene]–poly(ethylene oxide) blends

Polymer blends based on poly(vinylidene fluoride-co-trifluoroethylene) copolymers, P(VDF-TrFE), and poly(ethylene oxide), PEO, with varying compositions have been prepared by solvent casting. In this way, P(VDF-TrFE) crystallizes from the solution while solvent evaporates, while PEO crystallizes from the melt during cooling to room temperature. The surface morphology of the polymer blends indicates the transition from the fibrillar microstructure typical of PVDF-TrFE to the spherulite structure characteristic of PEO. The vibration mode characteristics of P(VDF-TrFE) are not influenced by the presence of PEO in the polymer blend. Confinement of PEO in the P(VDF-TrFE) phase change the conformation of PEO from trans to helix, increasing this transformation for increasing P(VDF-TrFE) content in the polymer blends. Sequential crystallization of the two polymers produce separated amorphous phases whose independent cooperative conformational motions are revealed by two main dynamic-mechanical relaxations. No chemical interaction seems to exist between the polymers within the blend.     

Ceramide–palmitic acid complex based Curcumin solid lipid nanoparticles for transdermal delivery: pharmacokinetic and pharmacodynamic study

Curcumin is an important anti-inflammatory natural compound with low bioavailability which is due to poor solubility and absorption. Solid lipid nanoparticles (SLNs) loaded with Curcumin were formulated and evaluated for physical parameters and in vitro/ex vivo permeation. Further the optimised SLN was assessed for pharmacokinetic/pharmacodynamic considerations. SLNs were formulated by emulsion-solvent evaporation technique and evaluated for physical properties and in vitro drug release. Selected SLNs were evaluated for stability and then characterised for pharmacokinetic parameters and anti-inflammatory activity with reference to a commercial formulation. Spherical SLNs were obtained in the size range of 102–156 nm with negative potential. C-SLN category has shown highest entrapment efficiency. The order of drug release was S-SLN > G-SLN > C-SLN. Selected SLN formulation C-SLN-3 has shown good stability under various conditions. C-SLN-3 has demonstrated highest drug permeation through human skin and 171.623 mg drug content permeated in 24 h. It has also shown lowest lag time 0.375 h. Similarly, it has shown maximum value for C_max in in vivo determination and increased the bioavailability upto 68.12%. C-SLN-3 provided 90.75% edema inhibition in 6 h. Present study shows that nature of lipids and its physical-chemical properties are critical for SLN formulation and can be used for designing better drug delivery systems with optimum transdermal permeation.