Nanodelivery of doxorubicin for age-related macular degeneration

Objective: Polymeric nanoparticles (NPs) containing doxorubicin (DOX) were prepared for the inhibition of hypoxia-induced factor 1α (HIF-1α).

Significance: HIF-1α is responsible for the upregulation of several angiogenic factors, including vascular endothelial growth factor (VEGF). DOX inhibits HIF-1α but is highly toxic. By encapsulating DOX in NPs, drug delivery will be sustained and toxicity will be reduced without limiting efficacy.

Methods: DOX NPs were prepared using both polylactic coglycolic acid (PLGA) and chitosan. PLGA NPs were prepared via nanoprecipitation (NPC) and single and double emulsion diffusion (SE; DE). Chitosan NPs were formulated using ionic gelation (IG), and complex coacervation (CC). Size, polydispersity index (PDI), and zeta potential (ZP) were determined via dynamic light scattering (DLS) (n?=?3). The encapsulation efficiency (EE), drug loading capacity (DLC) (n?=?3) and in vitro drug release profiles (IVR) at 37?°C (n?=?4) were analyzed via spectroscopy at 480?nm (λ_max). The cytotoxicity of each formulation as well as free DOX solution in ARPE-19 cells was determined via MTT assay after 24?h (n?=?3). HIF-1α and VEGF inhibition in ARPE-19 cells were measured via ELISA (n?=?3).

Results: The results were consistent with the hypothesis; the NP formulations decreased HIF-1α and VEGF-A expression in ARPE-19 cells with reduced cytotoxicity. SE, DE, and CC demonstrated low ZP as well as the most rapid drug release of the tested formulations. FTIR confirmed the presence of DOX on the SE NP surface, indicating instability.

Conclusions: SE, DE, and CC destabilized. NPC was the most efficient formulation for the nanodelivery of DOX for AMD.     

Imaging polarimetry in patients with neovascular age-related macular degeneration

Imaging polarimetry was used to examine different components of neovascular membranes in age-related macular degeneration. Retinal images were acquired with a scanning laser polarimeter. An innovative pseudocolor scale, based on cardinal directions of color, displayed two types of image information: relative phases and magnitudes of birefringence. Membranes had relative phase changes that did not correspond to anatomical structures in reflectance images. Further, membrane borders in depolarized light images had significantly higher contrasts than those in reflectance images. The retinal birefringence in neovascular membranes indicates optical activity consistent with molecular changes rather than merely geometrical changes.     

Binocular contrast inhibition in subjects with age-related macular degeneration.

In subjects with normal vision, binocular contrast sensitivity is generally higher than monocular sensitivity, indicating summation of contrast in the two eyes. We have compared monocular and binocular contrast sensitivity and acuity for a group of 13 subjects with age-related macular degeneration (AMD). Relative to a normal control group, many of the AMD subjects showed reduced binocular contrast summation, and binocular inhibition was found for eight subjects for a narrow or an extended frequency band. A better monocular than binocular function may have practical implications for reading and orientation in AMD.     

Nano-epoxy resins containing electrospun carbon nanofibers and the resulting hybrid multi-scale composites

For the first time, electrospun carbon nanofibers (ECNFs, with diameters and lengths of ∼200 nm and ∼15 μm, respectively) were explored for the preparation of nano-epoxy resins; and the prepared resins were further investigated for the fabrication of hybrid multi-scale composites with woven fabrics of conventional carbon fibers via the technique of vacuum assisted resin transfer molding (VARTM). For comparison, vapor growth carbon nanofibers (VGCNFs) and graphite carbon nanofibers (GCNFs) were also studied for making nano-epoxy resins and hybrid multi-scale composites. Unlike VGCNFs and GCNFs that are prepared by bottom-up methods, ECNFs are produced through a top-down approach; hence, ECNFs are more cost-effective than VGCNFs and GCNFs. The results indicated that the incorporation of a small mass fraction (e.g., 0.1% and 0.3%) of ECNFs into epoxy resin would result in substantial improvements on impact absorption energy, inter-laminar shear strength, and flexural properties for both nano-epoxy resins and hybrid multi-scale composites. In general, the reinforcement effect of ECNFs was similar to that of VGCNFs, while it was higher than that of GCNFs.     

Objective and subjective optical-quality measurements in subjects with keratitis and age-related macular degeneration

The use of commercial devices that objectively measure retinal image quality has increased in recent years although limited mostly to the analysis of surgical emmetropization techniques. In this work, we propose the use of optical-quality devices (an aberrometer and a double-pass device) to be extended to other highly prevalent ocular pathologies such as keratitis and age-related macular degeneration. For this, we determined whether the objective data correlate with visual performance. Data, including the contrast-sensitivity function, were taken for 26 patients. The results show a clear correspondence between objective and psychophysical measurements, revealing that optical-quality devices can be useful for additional visual clinical applications.     

纳米纤维素增强聚乙烯醇/水性聚氨酯静电纺膜的研究

采用TEMPO(2,2,6,6-四甲基哌啶氧化物自由基)氧化纤维素纳米纤维(TOCNs)作为聚乙烯醇(PVA)/水性聚氨酯(WPU)静电纺膜的增强剂。研究中使用拉伸实验研究TOCNs的增强作用,此外还使用扫描电子显微镜、红外光谱仪、热重分析仪及差示扫描量热仪等对静电纺膜进行结构性能表征。扫描电镜观察发现当纳米纤维素加入量为5%(质量分数)时,其在聚合物基质中分散良好,所得静电纺纳米纤维保持了良好的形态。此外,加入5%(质量分数)的纳米纤维素能够将材料的抗张强度提高44%,且纳米纤维素的加入对材料的热稳定性也有一定的改善,纳米纤维素起到一种纳米填料的效果。鉴于PVA、WPU、TOCNs均为亲水性,无毒且具有生物相容性的物质,所得静电纺膜在组织支架及伤口护理材料等方面具有潜在应用。     

Hybrid multi-scale composites developed from glass microfiber fabrics and nano-epoxy resins containing electrospun glass nanofibers

In this study, hybrid multi-scale composites were developed from glass microfiber fabrics (GFs) and nano-epoxy resins containing electrospun glass nanofibers (EGNFs). The hypothesis was that, through dispersing a small amount of EGNFs into epoxy resin, mechanical properties (particularly out-of-plane mechanical properties) of the resulting hybrid multi-scale composites would be significantly improved. The composites were fabricated by the technique of vacuum assisted resin transfer molding (VARTM). The interlaminar shear strength, flexural properties, impact absorption energy, and tensile properties of the composites were evaluated, and the results were compared to those acquired from GFs/epoxy composite as well as GFs/epoxy composites containing chopped glass microfibers (GMFs); additionally, the reinforcement and/or toughening mechanisms were investigated. The study revealed that the nano-epoxy resin with 0.25 wt.% of EGNFs resulted in substantial improvements on mechanical properties of the resulting hybrid multi-scale composites.     

Wet chemical process to enhance osteoconductivity of electrospun chitosan nanofibers

In this study, chitosan/hydroxyapatite (CS/HA) nanofibers were prepared using a wet chemical method. First, CS nanofibers with uniform diameters were fabricated using electrospinning. Then, a wet chemical process was used to mineralize nanofiber surfaces to form a homogeneous HA deposit. Reactions with three cycles were found to optimize biomimetic properties of the HA. The mineralization process required only approximately 3 h, which corresponded to a saving of 98 % in preparation time compared with that needed by the process using a simulated body fluid (SBF). According to the attachment and spreading of UMR (rat osteosarcoma) cells on the CS/HA composite fibers, the deposited mineralization layer significantly enhanced cell affinity of the CS nanofibers and the HA created by the wet chemical method was as effective as that created by the SBF. The composite nanofibrous scaffolds produced by the wet chemical process also promoted osteogenic differentiation by inducing ossification. Thus, expressions of collagen type I, alkaline phosphatase, osteocalcin, bone sialoprotein, and osterix were all enhanced. These results demonstrated that composite electrospun fibers can be efficiently prepared using wet chemical method and the resulting nanofibrous scaffolds have considerable potential in future bone tissue engineering applications.     

电纺纳米纤维自组装制备强磁性Fe_3O_4@SiO_2核壳结构纳米粒

通过电纺纤维自组装制备了具有强磁性敏感性的Fe3O4@SiO2复合纳米颗粒.电纺纤维的形貌通过扫描电镜(SEM)进行表征。纳米颗粒的尺寸分布,形貌和磁性分别通过FESEM、TEM和VSM进行确定。结果显示,该复合纳米颗粒具有近似球形的结构,并且具有多个磁性内核被包覆其中。纳米颗粒的尺寸大约为40 nm。Fe3O4@SiO2复合颗粒典型的比饱和磁化强度高达43.842 A·m2/kg,并且其在室温下具有超顺磁性。由于该磁性纳米颗粒具有强磁性敏感性,它们势必可以应用于更加广泛的领域。     

Cone photopigment in older subjects: decreased optical density in early age-related macular degeneration.

We measured changes to cone photoreceptors in patients with early age-related macular degeneration. The data of 53 patients were compared with normative data for color matching measurements of long- and middle-wavelength-sensitive cones in the central macula. A four-parameter model quantified cone photopigment optical density and kinetics. Cone photopigment optical density was on average less for the patients than for normal subjects and was uncorrelated with visual acuity. More light was needed to reduce the photopigment density by 50% in the steady state for patients. These results imply that cone photopigment optical density is reduced by factors other than slowed kinetics.     

Modification of the rotating jet method to generate highly aligned electrospun nanofibers

The rotating jet electrospinning method has been modified to increase the amount and the degree of alignment of electrospun nanofibers. For this purpose, the cylindrical collector of the rotating jet method (RJM) was replaced by two metallic concentric hollow cylinders. We called this improved technique; a modified rotating jet method (MRJM). The effectiveness of this method was evaluated with measuring the production rate and the degree of alignment of electrospun fibers and comparison of them with those obtained for the RJM. Our results disclosed that, the MRJM can improve the degree of alignment of electrospun fibers more than two times. Furthermore, when the voltage changed from 10 kV to 22 kV the average production rate of electrospun nanofibers was increased by 41% compared with the RJM.     

Preparation and photoluminescence properties of electrospun nanofibers containing PMO-PPV and Eu(ODBM)3phen

This communication explores a facile approach for fabricating nanofibers containing luminescent conjugated polymer, poly(2-methoxy-5-octoxy)-1,4-phenylene vinylene)-alt-1,4-(phenylene vinylene) (PMO-PPV), and rare earth complex, Eu(ODBM)₃phen (ODBM: 4-n-Octyloxydibenzoylmethanato; phen: 1,10-phenanthroline) via an electrospinning technique. The morphology and photoluminescent properties of the electrospun fibers were characterized by scanning electron microscopy, fluorescence spectrophotometer and UV optical microscopy. The electrospun fibers with diameters ranging from 70 nm to 200 nm as well as parallel orientation show strong green and red photoluminescence. This is the first but important approach towards novel applications of luminescent conjugated polymers and rare earth complex nanofibers. This kind of eletrospun nanofiber is a promising candidate for optical and electrical nanomaterials.     

Physical structure behavior to wettability of electrospun poly(lactic acid)/polysaccharide composite nanofibers

Poly(lactic acid) has been electrospun into submicron fibers with embedded cassava starch matrix. The fibers had average fiber diameters between 140 and 680?nm. The starch content varied from 10 to 20% in total solids. Water contact angles were measured on sheets of these fiber materials and correlated with the fiber size and starch content. Water contact angles varied from 80 to 120° which shows that the fiber composition can control the mat properties from hydrophilic to hydrophobic. The results also showed variation in the average fiber diameters alone did not always affect sheet wettability. These results show the importance of the relationship between the electrospun fiber sheet topography and material composition to the wettability of polysaccharide electrospun nanofibers.     

Hierarchical electrospun SiO2 nanofibers containing SiO2 nanoparticles with controllable surface-roughness and/or porosity

Herein we report that hierarchical electrospun SiO₂ nanofibers incorporated with SiO₂ nanoparticles with fiber diameters being ∼ 500 nm and particle sizes being tens of nanometers were developed through the combination of sol-gel process and electrospinning technique followed by high-temperature pyrolysis; and their morphologies and BET surface areas were examined. The study revealed that the pre-gelation of tetraethyl orthosilicate (TEOS) in spin dopes was important to achieve the morphological consistence of the electrospun precursor nanofibers and the resulting final SiO₂ nanofibers; additionally, SiO₂ nanoparticles appeared to be enriched on the fiber surface, while the surface-roughness and/or porosity of the nanofibers could be controlled through adjusting the incorporation amount of SiO₂ nanoparticles. The developed hierarchical electrospun SiO₂ nanofibers are expected to have important applications in composites (particularly dental composites) as well as catalyst support and adsorption.     

Chitin derived biochar as an alternative adsorbent to treat colored effluents containing methyl violet dye

Chitin was used to prepare an alternative, eco–friendly and low–cost adsorbent by a simple pyrolysis process. The adsorbent, named chitin derived biochar, was characterized and applied to treat colored effluents containing methyl violet dye (MV). Pyrolysis using N₂ flow rate of 0.25 L min^?1, heating rate of 10 °C min^?1 until 800 °C was suitable to prepare a chitin derived biochar with good characteristics. Chitin derived biochar presented surface area of 275.0 m² g^?1. The MV adsorption on the chitin derived biochar was favored in alkaline conditions and ambient temperature. The adsorption process presented fast kinetics and, the maximum adsorption capacity was higher than 1000 mg g^?1. Chitin derived biochar can be used for 7 consecutive adsorption/desorption cycles maintaining the same adsorption capacity. Also, the material was suitable to treat colored effluents, reaching color removal percentage of 95%. In brief, it was demonstrated that chitin derived biochar is a low–cost and efficient material to treat colored effluents.     

Plasma polymer coatings to aid retinal pigment epithelial growth for transplantation in the treatment of age related macular degeneration

Subretinal transplantation of functioning retinal pigment epithelial (RPE) cells grown on a synthetic substrate is a potential treatment for age-related macular degeneration (AMD), a common cause of irreversible vision loss in developed countries. Plasma polymers give the opportunity to tailor the surface chemistry of the artificial substrate whilst maintaining the bulk properties. In this study, plasma polymers with different functionalities were investigated in terms of their effect on RPE attachment and growth. Plasma polymers of acrylic acid (AC), allyl amine (AM) and allyl alcohol (AL) were fabricated and characterised using X-ray photoelectron spectroscopy (XPS) and water contact angle measurements. Octadiene (OD) hydrocarbon films and tissue culture polystyrene were used as controls. Wettability varied from hydrophobic OD to relatively hydrophilic AC. XPS demonstrated four very different surfaces with the expected functionalities. Attachment, proliferation and morphological examination of an RPE cell line and primary RPE cells were investigated. Both cell types grew on all surfaces, with the exception of OD, although the proliferation rate of primary cells was low. Good epithelial morphology was also demonstrated. Plasma polymerised films show potential as cell carrier surfaces for RPE cells in the treatment of AMD.