Reactive Oxygen Species-Responsive Delivery of a Notch Inhibitor to Alleviate Nonalcoholic Steatohepatitis by Inhibiting Hepatic de Novo Lipogenesis and Inflammation.

With the increased prevalence of nonalcoholic steatohepatitis (NASH) in the world, effective pharmacotherapy in clinical practice is still lacking. Previous studies have shown that dibenzazepine (DBZ), a Notch inhibitor, could alleviate NASH development in a mouse model. However, low bioavailability, poor water solubility, and extrahepatic side effects restrict its clinical application. To overcome these barriers, we developed a reactive oxygen species (ROS)-sensitive nanoparticle based on the conjugation of bilirubin to poly(ethylene glycol) (PEG) chains, taking into account the overaccumulation of hepatic ROS in the pathologic state of nonalcoholic steatohepatitis (NASH). The PEGylated bilirubin can self-assemble into nanoparticles in an aqueous solution and encapsulate insoluble DBZ into its hydrophobic cavity. DBZ nanoparticles (DBZ Nps) had good stability, rapidly released DBZ in response to H2O2, and effectively scavenged intracellular ROS of hepatocytes. After systemic administration, DBZ Nps could accumulate in the liver of the NASH mice, extend persistence in circulation, and improve the bioavailability of DBZ. Furthermore, DBZ Nps significantly improved glucose intolerance, relieved hepatic lipid accumulation and inflammation, and ameliorated NASH-induced liver fibrosis. Additionally, DBZ Nps had no significant extrahepatic side effects. Taken together, our results highlight the potential of the ROS-sensitive DBZ nanoparticle as a promising therapeutic strategy for NASH.

A black phosphorus nanosheet-based RNA delivery system for prostate cancer therapy by increasing the expression level of tumor suppressor gene PTEN via CeRNA mechanism.

BACKGROUND: Prostate cancer (PCa) has a high incidence in men worldwide, and almost all PCa patients progress to the androgen-independent stage which lacks effective treatment measures. PTENP1, a long non-coding RNA, has been shown to suppress tumor growth through the rescuing of PTEN expression via a competitive endogenous RNA (ceRNA) mechanism. However, PTENP1 was limited to be applied in the treatment of PCa for the reason of rapid enzymatic degradation, poor intracellular uptake, and excessively long base sequence to be synthesized. Considering the unique advantages of artificial nanomaterials in drug loading and transport, black phosphorus (BP) nanosheet was employed as a gene-drug carrier in this study. RESULTS: The sequence of PTENP1 was adopted as a template which was randomly divided into four segments with a length of about 1000 nucleotide bases to synthesize four different RNA fragments as gene drugs, and loaded onto polyethyleneimine (PEI)-modified BP nanosheets to construct BP-PEI@RNA delivery platforms. The RNAs could be effectively delivered into PC3 cells by BP-PEI nanosheets and elevating PTEN expression by competitive binding microRNAs (miRNAs) which target PTEN mRNA, ultimately exerting anti-tumor effects. CONCLUSIONS: Therefore, this study demonstrated that BP-PEI@RNAs is a promising gene therapeutic platform for PCa treatment.

Balanced chemical reactivity, antimicrobial properties and biocompatibility of decellularized dermal matrices for wound healing.

The prevention of bacterial infection and prompt wound repair are crucial considerations when local skin tissue is compromised by burns, cuts, or similar injuries. Porcine acellular dermal matrix (pADM) is a commonly employed biological material in wound repair due to its inherent natural properties. Nonetheless, the pADM's primary constituent, collagen fibers, lacks antimicrobial properties and is vulnerable to bacterial infection when used in the treatment of incompletely debrided wounds. Meanwhile, conventional antimicrobial agents primarily consist of chemical compounds that exhibit inadequate biocompatibility and biological hazards. This research endeavors to create an antimicrobial collagen scaffold dressing utilizing the Schiff base reaction through the incorporation of oxidized chitosan diquaternary (ODHTCC) salt into the pADM. Compared with the unmodified pADM, ODHTCC-pADM (OD-pA) still retained the three-stranded helical structure of natural collagen. At an ODHTCC cross-linker concentration of 4%, the thermal denaturation temperature of OD-pA was 85 °C. According to the enzymatic degradation resistance test in vitro, the degradation resistance of OD-pA to type I collagenase was significantly improved compared with that of the uncross-linked pADM. In addition, OD-pA exhibited good antibacterial properties, with inhibition rates of 95.6% and 99.9% for E. coli and Staphylococcus aureus, respectively, and a cytotoxicity level 1, meeting the in vitro requirements of national biomedical materials. In vivo experiments showed that the OD-pA scaffold could better promote wound healing and more effectively promote the positive expression of bFGF, PDGF and VEGF. In conclusion, OD-pA has struck a balance between antibacterial properties, chemical reaction properties and biocompatibility, ultimately achieving controllability, and has broad application prospects in the field of antibacterial biomedical materials.

C-terminal mini-PEGylation of a marine peptide N6 had potent antibacterial and anti-inflammatory properties against Escherichia coli and Salmonella strains in vitro and in vivo.

BACKGROUND: Enteropathogenic Escherichia coli and Salmonella pullorum are two important groups of zoonotic pathogens. At present, the treatment of intestinal pathogenic bacteria infection mainly relies on antibiotics, which directly inhibit or kill the pathogenic bacteria. However, due to long-term irrational, excessive use or abuse, bacteria have developed different degrees of drug resistance. N6, an arenicin-3 derivative isolated from the lugworm, has potent antibacterial activity and is poorly resistant to enzymatic hydrolysis and distribution in vivo. Polyethylene glycol (PEG) is an extensively studied polymer and commonly used in protein or peptide drugs to improve their therapeutic potential. Here, we modified the N-/C-terminal or Cys residue of N6 with liner PEGn of different lengths (n = 2, 6,12, and 24), and the effects of PEGylation of N6 on the stability, toxicity, bactericidal mechanism, distribution and efficacy were investigated in vitro and in vivo. RESULTS: The antimicrobial activity of the peptide showed that PEGylated N6 at the C-terminus (n = 2, N6-COOH-miniPEG) had potent activity against Gram-negative bacteria; PEGylated N6 at the N-terminus and Cys residues showed low or no activity with increasing lengths of PEG. N6-COOH-miniPEG has higher stability in trypsin than the parent peptide-N6. N6-COOH-miniPEG significantly regulated cytokine expression in lipopolysaccharides (LPS)-induced RAW 264.7 cells, and the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1ß were reduced by 31.21%, 65.62% and 44.12%, respectively, lower than those of N6 (-0.06%, -12.36% and -12.73%); N6-COOH-miniPEG increased the level of IL-10 (37.83%), higher than N6 (-10.21%). The data indicated that N6-COOH-miniPEG has more potent anti-inflammatory and immune-regulatory effect than N6 in LPS-stimulated RAW 264.7 cells. N6-COOH-miniPEG exhibited a much wider biodistribution in mice and prolonged in vivo half-time. FITC-labeled N6-COOH-miniPEG was distributed throughout the body of mice in the range of 0.75 - 2 h after injection, while FITC-labeled N6 only concentrated in the abdominal cavity of mice after injection, and the distribution range was narrow. N6-COOH-miniPEG improved the survival rates of mice challenged with E. coli or S. pullorum, downregulated the levels of TNF-α, IL-6, IL-1ß and IL-10 in the serum of LPS-infected mice, and alleviated multiple-organ injuries (the liver, spleen, kidney, and lung), superior to antibiotics, but slightly inferior to N6. CONCLUSIONS: The antibacterial activity, bactericidal mechanism and cytotoxicity of N6-COOH-miniPEG and N6 were similar. N6-COOH-miniPEG has a higher resistance to trysin than N6. The distribution of N6-COOH-miniPEG in mice was superior to that of N6. In exploring the modulatory effects of antimicrobial peptides on cytokines, N6-COOH-miniPEG had stronger anti-inflammatory and immunomodulatory effects than N6. The results suggested that C-terminal PEGylated N6 may provide an opportunity for the development of effective anti-inflammatory and antibacterial peptides.

Recurrent retinal detachment after pars plana vitrectomy with silicone oil tamponade for rhegmatogenous retinal detachment.

BACKGROUND: The recurrence of retinal detachment following rhegmatogenous retinal detachment (RRD) is a relatively common complication that can lead to reduced visual acuity and requires further surgery. The purpose of this study was to investigate the risk factors and visual outcomes of recurrent RRD following pars plana vitrectomy (PPV) with silicone oil tamponade for primary RRD. METHODS: This was a retrospective follow-up study of 343 eyes that underwent initial PPV surgery with silicone oil tamponade for primary RRD. Patients were divided into a recurrence group and a reattachment group. The main outcome measures included causative factors, visual outcomes related to the recurrence of RRD, and the perioperative factors most affecting the recurrence of RRD. RESULTS: After retinal reattachment, we observed RRD recurrence after PPV for primary RRD in 42 out of 343 eyes (12.2%) during the follow-up period. Most causes of recurrence (69%) occurred within 6 months of surgery. Multivariate logistic regression analysis showed that a PVR ≥ Grade C (odds ratio [OR]: 4.015; 95% confidence interval [CI] 1.721-9.367; P = 0.001) was a significant predictor for the development of recurrent RRD. Compared with the reattachment group, the recurrence group exhibited a significant decline in best-corrected visual acuity (BCVA) at the last follow-up visit (P = 0.000). Eyes with PVR prior to primary surgery, or at the diagnosis of re-detachment, showed a worse final BCVA. CONCLUSIONS: Our analysis shows that the predominant risk factor for the recurrence of RRD is a PVR ≥ Grade C. PVR prior to primary surgery, or at the diagnosis of re-detachment, was also shown to limit the recovery of final visual acuity.

Microgel Single-Cell Culture Arrays on a Microfluidic Chip for Selective Expansion and Recovery of Colorectal Cancer Stem Cells.

Cancer stem cells (CSCs) are rare and lack definite biomarkers, necessitating new methods for a robust expansion. Here, we developed a microfluidic single-cell culture (SCC) approach for expanding and recovering colorectal CSCs from both cell lines and tumor tissues. By incorporating alginate hydrogels with droplet microfluidics, a high-density microgel array can be formed on a microfluidic chip that allows for single-cell encapsulation and nonadhesive culture. The SCC approach takes advantage of the self-renewal property of stem cells, as only the CSCs can survive in the SCC and form tumorspheres. Consecutive imaging confirmed the formation of single-cell-derived tumorspheres, mainly from a population of small-sized cells. Through on-chip decapsulation of the alginate microgel, ∼6000 live cells can be recovered in a single run, which is sufficient for most biological assays. The recovered cells were verified to have the genetic and phenotypic characteristics of CSCs. Furthermore, multiple CSC-specific targets were identified by comparing the transcriptomics of the CSCs with the primary cancer cells. To summarize, the microgel SCC array offers a label-free approach to obtain sufficient quantities of CSCs and thus is potentially useful for understanding cancer biology and developing personalized CSC-targeting therapies.

[Association between S100B gene polymorphisms and hand, foot and mouth disease caused by enterovirus 71 infection].

OBJECTIVE: To investigate the association between rs9722 polymorphisms in the S100B gene and hand, foot and mouth disease (HFMD) caused by enterovirus 71. METHODS: A total of 124 HFMD children with enterovirus 71 infection were enrolled as subjects, and 56 healthy children were enrolled as control group. The rs9722 polymorphisms in the S100B gene were detected for both groups, and the serum level of S100B protein was measured for 74 HFMD children. RESULTS: The rs9722 locus of the S100B gene had three genotypes, CC, CT, and TT, and the genotype frequencies were in accordance with Hardy-Weinberg equilibrium. Compared with the control group, the HFMD group had significant increases in the frequencies of TT genotype and T allele (P<0.01). Children with severe HFMD caused by enterovirus 71 infection had significantly higher frequencies of TT genotype and T allele than those with moderate or mild HFMD (P<0.05). Compared with the cured patients, the patients with poor prognosis had significant increases in the frequencies of TT genotype and T allele in the rs9722 locus of the S100B gene (P<0.05). Among the 74 children with HFMD, the children with TT genotype had the highest serum level of S100B protein, and those with CC genotype had the lowest level (P<0.01). CONCLUSIONS: T allele in the rs9722 locus of the S100B gene might be a risk factor for severe HFMD caused by enterovirus 71 infection.

Efficient hemicellulose removal from lignocellulose by induced electric field-aided dilute acid pretreatment.

This study evaluated the effectiveness of induced electric field (IEF) as a novel electrotechnology to assist dilute acid pretreatment of wheat straw (WS) at atmospheric pressure and low temperature (90 °C). The effects of acid concentration and duration on cellulose recovery, hemicellulose and lignin removal were investigated. Meanwhile, the differences between IEF pretreatment and hydrothermal pretreatment were compared by quantitative and qualitative analysis. The optimal pretreatment condition was acid concentration 1 % with the period of 5 h. Under the parameters, the hemicellulose removal of WS after IEF pretreatment was up to 73.6 %, and the enzymatic efficiency was 55.8 %. In addition, the irregular surface morphology, diminished functional groups associated with hemicellulose, increased specific surface area and pore volume, as well as improved thermal stability of the residual WS support the remarkable effect of IEF pretreatment. The feasibility of IEF pretreatment is might be due to the fact that the magneto-induced electric field promotes ionization of H+ and formation of hydrated hydrogen ions, increasing the acidity of the medium. Secondly, electroporation disrupts the anti-degradation structure of WS and increases the accessibility of cellulose to cellulases. It indicated that IEF is a green and efficient strategy for assisting the separation of hemicellulose from lignocellulose.

Facile synthesis of a dimeric dipyrrole-polyamide and synergetic DNA-cleaving activity of its Cu(II) complex.

Inspired by the potent DNA-cleaving activity of the Cu(II) complex of monopyrrole-polyamide dimer 1 (i.e., 1@Cu(2+)), we designed a new dimeric dipyrrole-polyamide analog 2 with the aim to optimize the catalytic activities of the metal complexes of this type of polypyrrole-polyamides. Compound 2 was prepared in 50% yield from the reaction of 1-methyl-4-[(1-methyl-4-nitro-1H-pyrrole-2-carbonyl)-amino]-1H-pyrrole-2-carboxylic acid with 2,2'-(ethane-1,2-diylbis(oxy))diethanamine, and fully characterized on the basis of NMR ((1)H and (13)C), MS (ESI and HR) and IR. Spectrophotometric titration, ESI-MS and conductivity measurements indicated that compound 2 formed a 1:1 complex with Cu(2+) ion (i.e., 2@Cu(2+)). Agarose gel electrophoresis studies indicated that 2@Cu(2+) was capable of efficiently converting pBR322 DNA into open circular and linear forms under physiological conditions, most probably via an oxidative mechanism. Its overall catalytic activity was estimated to be at least 30-fold higher than that of 1@Cu(2+). The fact that the cleaving activities of these Cu(II) complexes parallel, exactly, their binding affinities, raises the possibility that the cleaving activities of polypyrrole-polyamide derivatives of the type can be regulated by the binding affinities.

[Clinical analysis of adenoid surgery in infancy].

Objective:To investigate the effects of postoperative surgical treatment of infantile adenoidal hypertrophy on children, the recurrence rate, and the changes in immune levels before and after surgery. Methods:Low temperature plasma ablation was performed in 11 infants with adenoidal hypertrophy to evaluate the risk of postoperative anesthesia and the effect of surgery on recurrence rate and immunity. Results:During the follow-up period of 3 to 6 months, 2 patients had recurrence（18.18%）, including 1 case with round pillow hyperplasia and 1 case with tonsil reactive hyperplasia. Three months after surgery, the immune level did not decrease significantly compared with that before surgery. No serious complications occurred in all children. Infants with adenoidal hypertrophy fall asleep, snoring, open mouth breathing, and belching seriously affect the quality of sleep and growth. Children who have been ineffective for more than 2 months undergo low-temperature plasma ablation. General anesthesia is safer. After that, the sleep quality of the children was significantly improved, and the immunity did not decrease significantly. Conclusion:Low temperature plasma ablation in infants with adenoidal hypertrophy is safe and effective, but it is not a routine treatment. Clinical symptoms are easy to repeat. The indications for surgery should be appropriately weighed.

WS2 nanosheets functionalized by biomimetic lipids with enhanced dispersibility for photothermal and chemo combination therapy.

Multi-component combination therapy of cancer is currently a hot spot in the field of cancer treatment research. In this study, a WS2 nanosheet was selected as the substrate material and modified with a cell-like membrane biomimetic liposome (WS2-lipid). The lipid-modified WS2 nanomaterials were successfully prepared with good stability and biocompatibility. Its good photothermal characteristics and high drug loading amount were utilized to achieve a comprehensive chemo and photothermal therapeutic effect. The results showed that the lipid coating strongly enhanced the stability of the WS2 nanosheets before and after DOX loading and the WS2-lipid had a good photothermal performance and drug loading amount. According to the cellular results, WS2-lipid was able to be taken up by MCF-7 cells. Both photothermo-therapy and chemotherapy had a concentration dependent cytotoxicity on MCF-7 cells, and the combined application of both methods had an improved cytotoxicity. In addition, in vivo photothermal experiments indicated that lipid modification could promote intratumoral accumulation of the material. Thus, WS2-lipid can be used as a good nano-platform for phototherapy and chemotherapy combination therapy and has good application prospects in cancer therapy.

Enhanced activity and stability of industrial lipases immobilized onto spherelike bacterial cellulose.

This study focused on improving activity and stability of industrial lipases by means of enzymatic immobilization onto spherelike bacterial cellulose (SBC) newly synthesized by a particular bacterial strain (Gluconacetobacter xylinus, JCM 9730). The results revealed that immobilizing lipases onto aldehyde-modified SBC with a size of 6.10±0.50mm could lead to two optimal hydrolytic activities of lipases under both acidic (pH 5) and alkaline conditions (pH 8), which was superior to free lipases that only exhibited an alkaline activity at pH 9. In addition, immobilizing lipases onto SBC could also achieve an improved active temperature below 30°C for lipases, which would help to reduce the energy consumption in the industrial production. Overall, this novel biomaterial has great potential as a green carrier for the immobilization of industrial lipases to enhance the recycling hydrolytic capability of oils and fats in various industrial divisions.

Biodegradable near-infrared-photoresponsive shape memory implants based on black phosphorus nanofillers.

In this paper, we propose a new shape memory polymer (SMP) composite with excellent near-infrared (NIR)-photoresponsive shape memory performance and biodegradability. The composite is fabricated by using piperazine-based polyurethane (PU) as thermo-responsive SMP incorporated with black-phosphorus (BP) sheets as NIR photothermal nanofillers. Under 808 nm light irradiation, the incorporated BP sheets with concentration of only 0.08 wt% enable rapid temperature increase over the glass temperature of PU and trigger the shape change of the composite with shape recovery rate of ∼100%. The in vitro and in vivo toxicity examinations demonstrate the good biocompatibility of the PU/BP composite, and it degrades naturally into non-toxic carbon dioxide and water from PU and non-toxic phosphate from BP. By implanting PU/BP columns into back subcutis and vagina of mice, they exhibit excellent shape memory activity to change their shape quickly under moderate 808 nm light irradiaiton. Such SMP composite enable the development of intelligent implantable devices, which can be easily controlled by the remote NIR light and degrade gradually after performing the designed functions in the body.

Surface Functionalization of Polymeric Nanoparticles with Umbilical Cord-Derived Mesenchymal Stem Cell Membrane for Tumor-Targeted Therapy.

Multiple cell plasma membranes have been utilized for surface functionalization of synthetic nanomaterials and construction of biomimetic drug delivery systems for cancer treatment. The natural characters and facile isolation of original cells facilitate the biomedical applications of plasma membranes in functionalizing nanocarriers. Human umbilical cord-derived mesenchymal stem cells (MSCs) have been identified to show tropism toward malignant lesions and have great advantages in ease of acquisition, low immunogenicity, and high proliferative ability. Here, we developed a poly(lactic- co-glycolic acid) (PLGA) nanoparticle with a layer of plasma membrane from umbilical cord MSC coating on the surface for tumor-targeted delivery of chemotherapy. Functionalization of MSC plasma membrane significantly enhanced the cellular uptake efficiency of PLGA nanoparticles, the tumor cell killing efficacy of PLGA-encapsulated doxorubicin, and most importantly the tumor-targeting and accumulation of the nanoparticles. As a result, this MSC-mimicking nanoformulation led to remarkable tumor growth inhibition and induced obvious apoptosis within tumor lesions. This study for the first time demonstrated the great potential of umbilical cord MSC plasma membranes in functionalizing nanocarriers with inherent tumor-homing features and the high feasibility of such biomimetic nanoformulations in cancer therapy.

Delivery of small interfering RNA against Nogo-B receptor via tumor-acidity responsive nanoparticles for tumor vessel normalization and metastasis suppression.

Nogo-B receptor (NgBR) plays fundamental roles in regulating angiogenesis, vascular development, and the epithelial-mesenchymal transition (EMT) of cancer cells. However, the therapeutic effect of NgBR blockade on tumor vasculature and malignancy is unknown, investigations on which requires an adequate delivery system for small interfering RNA against NgBR (NgBR siRNA). Here a surface charge switchable polymeric nanoparticle that was sensitive to the slightly acidic tumor microenvironment was developed for steady delivery of NgBR siRNA to tumor tissues. The nanoformulation was constructed by conjugating 2, 3-dimethylmaleic anhydride (DMMA) molecules to the surface amines of micelles formed by cationic co-polymer poly(lactic-co-glycolic acid)2-poly(ethylenimine) and subsequent absorption of NgBR siRNAs. The nanoparticles remained negatively charged in physiological condition and smartly converted to positive surface charge due to tumor-acidity-activated shedding of DMMA. The charge conversion facilitated cellular uptake of siRNAs and in turn efficiently depleted the expression of NgBR in tumor-bearing tissues. Silencing of NgBR suppressed endothelial cell migration and tubule formation, and reverted the EMT process of breast cancer cells. Delivery of the nanoformulation to mice bearing orthotopic breast carcinoma showed no effect on tumor growth, but led to remarkable decrease of distant metastasis by normalizing tumor vessels and suppressing the EMT of breast cancer cells. This study demonstrated that NgBR is a promising therapeutic target in abnormal tumor vasculature and aggressive cancer cells, and the tumor-responsive nanoparticle with the feature of charge transformation offers great potential for tumor-specific delivery of gene therapeutics.

Field-Free Isolation of Exosomes from Extracellular Vesicles by Microfluidic Viscoelastic Flows.

Exosomes, molecular cargos secreted by almost all mammalian cells, are considered as promising biomarkers to identify many diseases including cancers. However, the small size of exosomes (30-200 nm) poses serious challenges in their isolation from complex media containing a variety of extracellular vesicles (EVs) of different sizes, especially in small sample volumes. Here we present a viscoelasticity-based microfluidic system to directly separate exosomes from cell culture media or serum in a continuous, size-dependent, and label-free manner. Using a small amount of biocompatible polymer as the additive in the media to control the viscoelastic forces exerted on EVs, we are able to achieve a high separation purity (>90%) and recovery (>80%) of exosomes. The proposed technique may serve as a versatile platform to facilitate exosome analyses in diverse biochemical applications.

Topography, Wettability, and Electrostatic Charge Consist Major Surface Properties of Intraocular Lenses.

PURPOSE: To quantify potential relevant factors that affect the biocompatibility and functionality of intraocular lenses (IOLs) by analyzing the surface properties of various IOL materials. METHODS: Eleven IOL models with the same dioptric power made by different manufacturers were studied. The IOLs were made of poly-methyl methacrylate (PMMA), hydrophobic acrylate, hydrophilic acrylate, and silicone. The IOL surface topography was evaluated using atomic force microscopy (AFM). Surface potential was measured by electric force microscopy (EFM). Surface wettability was assessed with the water contact angle using the sessile drop method. RESULTS: The PMMA IOLs had statistically significant surface irregularities with the highest surface roughness values while the silicone and hydrophilic acrylic IOLs had the lowest values. Surface potentials on IOLs revealed that all IOL models made of PMMA had positive charge. The hydrophobic acrylic IOL had a significantly higher positive charge (6.2v ± 0.1v), while the hydrophobic acrylic with blue blocker exhibited negative charge. Negative charge was also observed on hydrophilic acrylic IOLs (-72mv ± 5mv) and silicone IOLs (-5.06v ± 0.02v). Contact angle values of PMMA IOLs ranged from 49° to 64°. Heparin modification resulted in significant reduction of the contact angle value. IOL models made of hydrophobic acrylate had contact angle values between 78° and 89°. The silicone IOL appeared to be significantly hydrophobic with the highest mean value of 107°. CONCLUSIONS: The variance of the parameters of surface roughness, contact angle, and electrostatic charge on the surfaces of PMMA, hydrophobic acrylic, hydrophilic acrylic, and silicone IOLs is useful to the interpretation of the differences in clinical behaviors of these materials. The negative surface charge of silicone and hydrophilic IOLs might account for the occurrence of IOL calcification.

Nanostructured lipid carrier surface modified with Eudragit RS 100 and its potential ophthalmic functions.

This study was carried out to evaluate the ocular performance of a cationic Eudragit (EDU) RS 100-coated nanostructured lipid carrier (NLC). The genistein encapsulated NLC (GEN-NLC) was produced using the melt-emulsification technique followed by surface absorption of EDU RS 100. The EDU RS 100 increased the surface zeta potential from -7.46 mV to +13.60 mV, by uniformly forming a spherical coating outside the NLC surface, as shown by transmission electron microscopy images. The EDU RS 100 on the NLC surface effectively improved the NLC stability by inhibiting particle size growth. The obtained EDU RS 100-GEN-NLC showed extended precorneal clearance and a 1.22-fold increase in AUC (area under the curve) compared with the bare NLC in a Gamma scintigraphic evaluation. The EDU RS 100 modification also significantly increased corneal penetration producing a 3.3-fold increase in apparent permeability coefficients (Papp) compared with references. Draize and cytotoxicity testing confirmed that the developed EDU RS 100-GEN-NLC was nonirritant to ocular tissues and nontoxic to corneal cells. These results indicate that the NLC surface modified by EDU RS 100 significantly improves the NLC properties and exhibits many advantages for ocular use.

Size-dependent in vivo toxicity of PEG-coated gold nanoparticles.

BACKGROUND: Gold nanoparticle toxicity research is currently leading towards the in vivo experiment. Most toxicology data show that the surface chemistry and physical dimensions of gold nanoparticles play an important role in toxicity. Here, we present the in vivo toxicity of 5, 10, 30, and 60 nm PEG-coated gold nanoparticles in mice. METHODS: Animal survival, weight, hematology, morphology, organ index, and biochemistry were characterized at a concentration of 4000 µg/kg over 28 days. RESULTS: The PEG-coated gold particles did not cause an obvious decrease in body weight or appreciable toxicity even after their breakdown in vivo. Biodistribution results show that 5 nm and 10 nm particles accumulated in the liver and that 30 nm particles accumulated in the spleen, while the 60 nm particles did not accumulate to an appreciable extent in either organ. Transmission electron microscopic observations showed that the 5, 10, 30, and 60 nm particles located in the blood and bone marrow cells, and that the 5 and 60 nm particles aggregated preferentially in the blood cells. The increase in spleen index and thymus index shows that the immune system can be affected by these small nanoparticles. The 10 nm gold particles induced an increase in white blood cells, while the 5 nm and 30 nm particles induced a decrease in white blood cells and red blood cells. The biochemistry results show that the 10 nm and 60 nm PEG-coated gold nanoparticles caused a significant increase in alanine transaminase and aspartate transaminase levels, indicating slight damage to the liver. CONCLUSION: The toxicity of PEG-coated gold particles is complex, and it cannot be concluded that the smaller particles have greater toxicity. The toxicity of the 10 nm and 60 nm particles was obviously higher than that of the 5 nm and 30 nm particles. The metabolism of these particles and protection of the liver will be more important issues for medical applications of gold-based nanomaterials in future.

Iron and manganese removal by using manganese ore constructed wetlands in the reclamation of steel wastewater.

To reclaim treated steel wastewater as cooling water, manganese ore constructed wetland was proposed in this study for the removal of iron and manganese. In lab-scale wetlands, the performance of manganese ore wetland was found to be more stable and excellent than that of conventional gravel constructed wetland. The iron and manganese concentration in the former was below 0.05 mg/L at hydraulic retention time of 2-5 days when their influent concentrations were in the range of 0.16-2.24 mg/L and 0.11-2.23 mg/L, respectively. Moreover, its removals for COD, turbidity, ammonia nitrogen and total phosphorus were 55%, 90%, 67% and 93%, respectively, superior to the corresponding removals in the gravel wetland (31%, 86%, 58% and 78%, respectively). The good performance of manganese ore was ascribed to the enhanced biological manganese removal with the aid of manganese oxide surface and the smaller size of the medium. The presence of biological manganese oxidation was proven by the facts of good manganese removal in wetlands at chemical unfavorable conditions (such as ORP and pH) and the isolation of manganese oxidizing strains from the wetlands. Similar iron and manganese removal was later observed in a pilot-scale gravel-manganese-ore constructed wetland, even though the manganese ore portion in total volume was reduced from 100% (in the lab-scale) to only 4% (in the pilot-scale) for the sake of cost-saving. The quality of the polished wastewater not only satisfied the requirement for cooling water but also suitable as make-up water for other purposes.