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.     

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.     

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.     

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.     

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.     

Brittle–ductile transition behavior of poly(ethylene terephthalate)/poly(ethylene-octene) blend: the roles of compatibility and test temperature

In this study, we attempted to elucidate the Brittle–ductile transition (BDT) behavior of poly(ethylene terephthalate) (PET)/poly(ethylene-octene) (POE) blends under different situations of interfacial compatibility and test temperature. To modulate the compatibility between PET and PEO, maleic anhydride grafted POE (mPOE) was selected as compatibilizer. Three kinds of elastomeric additives, 100 % POE, mPOE/POE (15/85 w/w), and 100 % mPOE, were blended with PET, resulting in three compatibility situations, namely, poor, moderate, and strong interfacial adhesion, respectively. The impact toughness as a function of elastomer content was measured under different interfacial adhesions and test temperature, and microscopic morphology was revealed by scanning electron microscopy and transmission electron microscopy. The results indicated that the interfacial adhesion determines the fashion of microvoiding and even the matrix shear yielding deformation, which will significantly affect the BDT behavior and its response to test temperature. Our study provides not only an effective route to prepare supertoughened PET blends (improved for 20 folds as comparing to the neat PET), but also a fresh insight into the importance of interfacial adhesion on the toughening of thermoplastic/elastomer system.     

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.     

Folate-mediated solid–liquid lipid nanoparticles for paclitaxel-coated poly(ethylene glycol)

Background: As a promising anticancer drug, severe side-effects of current clinical formulations for paclitaxel have restricted its use, developing a better technical-economical formulation for paclitaxel delivery is needed. Method: In this study, the compound of folate-poly(ethylene glycol) (PEG)-phosphatidylethanolamine was synthesized and characterized with Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. The solid-liquid lipid nanoparticle (SLLN) for paclitaxel modified with folate and poly(ethylene glycol) (folate-PEG-SLLN) was prepared and characterized. Morphology of folate-PEG-SLLN was examined by transmission electron microscopy. The particle size and zeta potential were performed by Zetapals. Encapsulation efficiency was analyzed by HPLC. The in vitro drug release of paclitaxel was investigated via membrane dialysis. The in vivo pharmacokinetics was measured with male Sprague-Dawley rats. Treatment efficiency was investigated with the mouse with sarcoma180 ascites tumor. Results: Paclitaxel loaded on the newly designed binary SLLN showed a longer and sustained in vitro releasing property. More importantly, S180 tumor-bearing mice treated with paclitaxel-loaded SLLN exhibited higher tumor inhibition rate, comparing with animals administered with paclitaxel injection alone (45.3% and 37.3%, respectively). Conclusion: The newly developed paclitaxel delivery system may have improved in vivo antitumor activity. The results demonstrated a great interest to use folate-mediated SLLN as a prospective drug delivery system for paclitaxel.     

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.     

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.     

Structure,swelling, and drug release of thermoresponsive poly(amidoamine) dendrimer–poly(N-isopropylacrylamide) hydrogels

Functional drug delivery systems are important for improved pharmacotherapy. The aim of this work was to describe how the introduction of varying amounts of the dendrimer polyamidoamine (PAMAM) into a chemically cross-linked thermoresponsive poly(N-isopropylacrylamide) (PNIPAAM) gel affects the structure, swelling properties, and drug release characteristics. The structure of the gel system was characterized by small-angle X-ray scattering (SAXS), while the drug delivery system was characterized by measuring the swelling, loading, and release of the model drug. The SAXS results suggest that the PNIPAAM gel is heterogeneous on a local length scale, whereas more homogeneous gels are formed in the presence of PAMAM. Increased swelling and loading capacity were observed for higher fractions of PAMAM dendrimer. This was explained by the enhanced hydrophilicity obtained by inclusion of the dendrimers. The swelling process was observed to be very slow taking place over several days, indicating other mechanisms than diffusion to be the rate-limiting step. The temperature-induced deswelling was more pronounced for the dendrimer-containing formulations. This process was observed to be very fast and complete within a couple of hours. Similarly the release rate was quite fast without being affected by inclusion of the dendrimer. Retention of a significant portion of the loaded drug at specific conditions was shown to be due to the hydrogen bonding ability of PNIPAAM. Improved conditions for drug delivery were achieved in several respects by incorporation of PAMAM dendrimer molecules in the PNIPAAM hydrogel. Our results indicate that the PAMAM entities expand the PNIPAAM gel and that the gel becomes more homogeneous.     

Size- and shape-controlled synthesis of colloidal gold through autoreduction of the auric cation by poly(ethylene oxide)-poly(propylene oxide) block copolymers in aqueous solutions at ambient conditions

Gold nanoparticles with an average diameter in the range 5-20?nm have been synthesized from hydrogen tetrachloroaureate (III) hydrate (HAuCl(4)·3H(2)O) in air-saturated aqueous PEO-PPO-PEO block copolymer solutions at ambient temperature in the absence of any other reducing agent (PEO: poly(ethylene oxide), PPO: poly(propylene oxide)). The particle size was controlled by the block copolymer concentration and PEO and PPO block lengths. Our findings indicate that longer PEO blocks lead to an increase in particle size because of an increase in reaction activity. Adsorption of PO segments on gold nanoparticles seems to prevent particle growth from aggregation, and results in small particle size and high colloidal stability. An increase of the HAuCl(4) concentration causes a change in the particle shape from spherical to triangular or hexagonal nanoplates.     

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).     

Synthesis, characterization and hydrolytic degradation study of polyetheresteramide copolymers based on ε-caprolactone, 6-aminocaproic acid, and poly(ethylene glycol)

In this paper, a new kind of biodegradable aliphatic polyetheresteramide copolymers (PEEA) based on -caprolactone, 6-aminocaproic acid, and poly(ethylene glycol) (PEG) were synthesized by melt polymerization method. The obtained copolymers were characterized by ¹H-NMR. The thermal properties of PEEA copolymers were studied by DSC and TGA/DTA under nitrogen atmosphere. The water absorption and hydrolytic degradation behavior was also studied in detail. With the increase in PEG content or the decrease in caprolactone content, the water absorption of the copolymers increased accordingly. For the hydrolytic degradation behavior, with the increase in PEG content or caprolactone content, the degradation rate increased then.     

Mechanical behaviour of block copolymers of polyurethane with poly (4,4′-diphenylsulphone terephthalamide)

Two poly (tetramethylene glycols) (PTMG), molecular weight of 650 and 2000, with 4,4-diphenylmethane diisocyanate (MDI) and poly(4, 4-diphenylsulphone terephthalamide) (PSA) prepolymer were polycondensated. Four different molar ratios of PTMG, MDI and PSA prepolymer were synthesized to form eight PU-PSA block copolymers. The mechanical properties including stress-strain and stress-relaxation measurements of each copolymer were discussed. The determined values of Young's modulus E, Mooney-Rivlin relation elastic parameters C1 and C2, relaxation moduli E1(0) and E2(0), relaxation time 1 and 2 were used to estimate the effect of hard segment and soft segment domains on the mechanical behaviour of copolymers. It was found that PU-PSA block copolymers apparently displayed elastic properties, especially using the molecular weight 2000 of PTMG which exhibited more elastic behaviour.     

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.     

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.     

Dielectric constant and refractive index of poly (siloxane–imide) block copolymer

Recent technological advances demanded polyimides of improved versatility in terms of electronic, optical and thermal properties. In this work, a series of poly(siloxane–imide) block copolymers were synthesized in order to investigate the effect on their optical and electronic properties. The polyimide unit was derived from 3,3′,4,4′-Biphenyltetracarboxylic dianhydride (BPDA) and 4-(4-{1-[4-(4-aminophenoxy) phenyl]-1-methylethyl} phenoxy) aniline (BAPP) while the siloxane unit was derived from 3-[3-(3-aminopropyl)-1,1,3,3-tetramethyldisiloxanyl] propylamine (DMS) and Poly(dimethylsiloxane), bis(3-aminopropyl)terminated (PDMS). The structure of the polyimide was characterized by fourier transformer infra red (FT-IR), nuclear magnetic resonance (NMR) spectroscopy, elemental analysis, solution viscosity and gas permeation chromatography (GPC). Scanning electron microscope (SEM) analysis suggested a microphase separation between the two components. The refractive index and dielectric properties showed a decreasing trend with increased silicone unit in the polyimide backbone. However ultra violet visible (UV–Vis) and optical transparency was not significantly affected. Electronic and optical properties of this copolymer were discussed in relation to the polysiloxane content.