NPs Groups Research Articles

Inflamed site-specific drug delivery system based on the interaction of human serum albumin nanoparticles with myeloperoxidase in a murine model of experimental colitis

To develop a new strategy for inflamed site-specific drug delivery in the colon for the treatment of ulcerative colitis (UC), we leveraged on the interaction between myeloperoxidase (MPO) and human serum albumin (HSA) and prepared nanoparticles (HSA NPs) conjugated with 5-aminosalicylic acid (5-ASA). The 5-ASA-HSA NPs (nine molecules of 5-ASA per HSA molecule) were uniform particles with an average particle size of 190 nm, a zeta potential of -−11.8 mV, and a polydispersity index of 0.35. This was considered a suitable particle characteristic to pass through the mucus layer and accumulate into the mucosa. The specific interaction between the 5-ASA-HSA NPs and MPO was observed using quartz crystal microbalance analysis in vitro. In addition, the 5-ASA-HSA NPs group containing one thousandth of the dose of the 5-ASA (75 μg/kg) showed significantly lower disease activity index values and colon weight/length ratios in UC model mice as similar to large amount of neat 5-ASA group (75 mg/kg), indicating that the therapeutic effect of the 5-ASA-HSA NP formulation was confirmed in vivo. Microscopic images of tissue sections of colon extracted from UC model mice demonstrated that HSA NPs and MPO were both localized in the colon, and this specific interaction between HSA NPs and MPO would be involved the in the therapeutic effect in vivo. Furthermore, in the 5-ASA and 5-ASA-HSA NPs groups, some inflammatory damage was observed in the colon, but the degree of damage was mild compared with the control and HSA NPs groups, suggesting mucosal repair and replacement with fibrous granulation tissue had occurred. Therefore, these data demonstrated that an HSA NP formulation has the potential to specifically deliver 5-ASA to an inflamed site where MPO is highly expressed.

Combined effect of silver nanoparticles and honey in experimental wound healing process in rats

Background: Wounds are still major problem in developing countries, and may impose severe complications and high cost for therapy. Hence, wound management still remains an important focus of researches. Plastic catheters coated with SNPs prevent biofilm formation. Papaya possesses antibacterial activity which might prevent the multiplication of wound infection causing bacteria. The objective of this study was to combined effect of honey and silver nanoparticles increases the rate of healing in wounds infected by Pseudomonas aeruginosa. Material and Methods: Eighteen healthy adult male Wistar albino rats weighing 250-300 g were used in this study. Excision wound model was used for this study. A wound of 500 mm2 was created using a sterile scalpel by removing the skin on the dorsum of the abdomen of the all group. Clinical assessments included observations concerning the appearance, and the wound size was measured. Results: The wound in all the three groups were almost same in the beginning. The percentage of wound closure on the fifth day was 0.86 ± 0.11, 0.91 ± 0.18 and 0.95 ± 0.07, On d 10 still better wound closure was observed with a percentage there was a significant increase in healing and the percentage closure was 0.76 ± 0.20, 70.2 ± 0.19 and 71.15 ± 0.18 (P<0.001), on d 15 the wound closure percentage was 20.18 ± 0.18, 89.21 ± 0.18 and 94. 31 ± 0.20 (P<0.001), for control, honey treated and honey ± Ag Nps groups respectively with a high significance from control. Conclusion: This study demonstrated the efficacy of multifloral honey mixed with silver nanoparticles in wound healing. Topical application of multifloral honey with silver nanoparticles accelerated the rate of wound healing by increasing the wound contraction compared with honey. The acceleration of wound healing rate and wound contraction through macroscopic and histological evolution on d 1, 5, 10 and 15. Hence, honey mixed with silver nanoparticles is potentially useful in dressing wounds.

Piperine-loaded chitosan-STPP nanoparticles reduce neuronal loss and astrocytes activation in chemical kindling model of epilepsy

Recent evidence suggests that encapsulation of hydrophobic drugs in biodegradable polymers opens a new horizon in nanomedicine filed. Piperine, a main alkaloid form of black pepper possesses potent anticonvulsant activity. However, the low water solubility of piperine has limited its clinical application. In this study, piperine was loaded on chitosan-sodium tripolyphosphate nanoparticles (CS-STPP NPs) and the effect of piperine NPs on seizures behavior and astrocytes activation was assessed in pentylentetrazol (PTZ)-induced kindling model. Animals have received the daily injection of free piperine or piperine NPs at doses of 5 or 10mg/kg, 10days before PTZ injections and their intraperitoneally (i.p) administration continued until the last PTZ injection. The neuroprotective effects of piperine NPs were evaluated using nissl staining and immunostaining against NeuN. Astrocytes activation was examined by GFAP immunostaining. Behavioral data showed that piperine NPs have inhibited the development of seizure parameters compared to the free piperine groups. In addition, the levels of cell loss and astrocytes activation were reduced in piperine NPs groups. In conclusion, these data suggest that piperine NPs enhance the neuroprotection and ameliorate the astrocytes activation in chemical kindling model of epilepsy. This may provide an effective therapeutic strategy for the treatment of epilepsy disorder.

Preparation of high toughness nanocomposite hydrogel with UV protection performance and self-healing property

An ultraviolet shielding hydrogel of P(NaSS-co-MPTC)/TiO2 was prepared by introducing TiO2 nanoparticles (TiO2 NPS) into polyampholyte matrix through photo-initiated radical copolymerization of cationic monomer of 3-(methacrylamide) propyltrimethylammonium chloride (MPTC) and anionic monomer of sodium 4-vinylbenzenesulfonate (NaSS) in the aqueous solution of sodium chloride (NaCl). FTIR, XPS, TEM, XRD, and SEM were used to characterize the morphology and structure of hydrogel of P(NaSS-co-MPTC)/TiO2. The result showed that anatase TiO2 NPS with the size about 15 ~ 20 nm were not just acted as ultraviolet shielding agent and general photo-initiator, they also could be crosslinked in polyampholyte matrix by hydrogen bonding between hydroxyl groups on the surface of TiO2 NPS and sulfonate groups on the polymer chains. Based on two kinds of reversible weak bonds of hydrogen bond and ionic bond, the P(NaSS-co-MPTC)/TiO2 hydrogel exhibited excellent mechanical properties and self-healing ability at ambient conditions, which will greatly increase its service life being a UV inhibitor.

Investigation of the clinical features of geographic tongue: unveiling its relationship with oral psoriasis.

Few studies have examined the clinical features of geographic tongue (GT), an inflammatory lesion, making diagnosis and the investigation of oral psoriasis difficult. To investigate the clinical features of GT to facilitate its identification and understand its relationship with psoriasis. A total of 96 participants diagnosed with GT underwent stomatological and dermatological examinations. The parameters assessed were burning sensation; number, classification, and location of lesions; loss of papillae; severity of GT lesions; and association with fissured tongue (FT). Psoriatic patients (PS) and those without psoriasis (NPS) were compared. Burning sensation was reported by 45 (47%) patients, 67 (70%) patients showed active GT, 68 (71%) presented with typical lesions, and 59 (61%) exhibited moderate lesions. GT was associated with FT in 75% of the cases and exhibited a diffused pattern associated with severe lesions. It was also more frequent in the PS group. The comparative analysis between the PS and NPS groups showed significant differences between the groups with regard to gender, presence of burning sensation, and GT severity. GT is a symptomatic lesion with a thick halo. In contrast, psoriatic patients are frequently asymptomatic and exhibit severe lesions with greater loss of papillae that are associated with severe FT. The present study is the first to demonstrate clinical differences in the GT of patients with and without psoriasis, suggesting that some GT cases may represent true oral psoriasis and some cases may represent only GT.

5-ASA-loaded SiO2 nanoparticles-a novel drug delivery system targeting therapy on ulcerative colitis in mice.

The targeting of 5-aminosalicylic acid (5-ASA), a first-line therapeutic agent for mild to moderate active ulcerative colitis (UC), to the site of inflammation has remained a challenge and an unmet requirement in the treatment of UC. However, nanoscale carriers for targeted drug delivery are promising for pharmacotherapy, and nanoparticles improve the pharmacokinetics of the loaded therapeutics based on their physical properties. To design and prepare 5-ASA-loaded silicon dioxide nanoparticles (5-ASA-SiO2 NPs), a micro-emulsion method was conducted, and their respective therapeutic effects were validated in a mouse model of UC. Cytotoxicity of 5-ASA-SiO2 NPs was detected in vitro using the Cell Counting Kit-8 method. The therapeutic effect of 5-ASA-SiO2 NPs was assessed based on their disease activity index (DAI), colon histopathology, myeloperoxidase (MPO) and levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). SiO2 NPs were successfully prepared, and cytotoxicity of 5-ASA-SiO2 NPs was identified as being similar to 5-ASA and SiO2 NPs. DAI and colonic histopathology scores in the normal dosage, high dosage and the 5-ASA-SiO2 NP groups demonstrated a significant improvement when compared with the model group. DAI in the high dosage and 5-ASA-SiO2 NP groups also demonstrated a significant improvement when compared with the normal dosage group. However, MPO, serum IL-6 and TNF-α levels in normal dosage, high dosage and 5-ASA-SiO2 NPs groups were significantly lower than in the model group, and these indexes in the high dosage group and 5-ASA-SiO2 NP group were significantly lower than that in the normal dosage group. Expression of IL-6 and TNF-α mRNA in colonic mucosa in the normal dosage, high dosage and 5-ASA-SiO2 NP group was significantly lower than that in the model group. Colonic mucosal IL-6 and TNF-α mRNA expression in the high dosage and 5-ASA-SiO2 NP groups was significantly lower than that in the normal dosage group (P<0.05). In conclusion, 5-ASA-SiO2 NPs are a selective drug release system that target the inflamed colon, characteristics of UC, and can greatly increase therapeutic efficacy in UC.

IRGD-mediated core-shell nanoparticles loading carmustine and O6-benzylguanine for glioma therapy

iRGD (internalizing RGD) with high affinity to αν integrins was reported to enhance tumor penetrability by binding to neuropilin-1 (NRP-1). Based on our previous study, chitosan surface-modified poly (lactide-co-glycolides) nanoparticles (PLGA/CS NPs), loaded with carmustine (BCNU) and its sensitizer (O6-benzylguanine, BG) showed stronger anti-tumor effect than free drugs. In present study, PLGA/CS NPs (NPs) with core-shell structure were prepared and modified with iRGD or mPEG. F98, C6 or U87 cell lines with different receptors levels were selected for in vitro and in vivo studies. After administration of iRGD-mediated NPs, including iRGD-modified NPs (iRGD-NPs) and co-administration of iRGD and NPs (iRGD + NPs), their effects on glioma were compared with NPs. iRGD-NPs showed stronger cytotoxicity and cellular uptake than other groups. iRGD-NPs and iRGD + NPs displayed deeper tumor penetration and stronger anti-invasion effect on three dimensional (3D) glioma spheroids than NPs. On F98 glioma-bearing mice model, iRGD-mediated NPs showed enhanced crossing BBB ability and brain tumor accumulation levels. Correspondingly, the median survival time of iRGD + NPs, iRGD-NPs and NPs groups were 58, 49 and 34.5 days, respectively. Present studies supported the iRGD-mediated strategy to improve the efficacy of antitumor drug delivery system. Importantly, co-administration of iRGD may be a greater way over the conjugation of iRGD.

Prior Sternotomy Increases the Mortality and Morbidity of Adult Heart Transplantation

BackgroundThis study investigated the effect of prior sternotomy (PS) on the postoperative mortality and morbidity after orthotopic heart transplantation (HTx). MethodsOf 704 adults who underwent HTx from December 1988 to June 2012 at a single institution, 345 had no PS (NPS group) and 359 had ≥1 PS (PS group). Survival, intraoperative use of blood products, intensive care unit (ICU) and hospital stays, frequency of reoperation for bleeding, dialysis, and >48-hour ventilation were examined. ResultsThe NPS and PS groups had similar 60-day survival rates (97.1 ± 0.9% vs 95.3 ± 1.1%; P = .20). However, the 1-year survival was higher in the NPS group (94.7 ± 1.2% vs 89.7 ± 1.6%; hazard ratio [HR], 1.98; 95% CI, 1.12–3.49; P = .016). The PS group had longer pump time and more intraoperative blood use (P < .0001 for both). Postoperatively, the PS group had longer ICU and hospital stays, and higher frequencies of reoperation for bleeding and >48-hour ventilation (P < .05 for all comparisons). Patients with 1 PS (1PS group) had a higher 60-day survival rate than those with ≥2 PS (2+PS group; 96.7 ± 1.1% vs 91.1 ± 3.0%; HR, 2.70; 95% CI, 1.04–7.01; P = .033). The 2+PS group had longer pump time and higher frequency of postoperative dialysis (P < .05 for both). Patients with prior VAD had lower 60-day (91.1 ± 3.0% vs 97.1 ± 0.9%; P = .010) and 1-year (87.4 ± 3.6% vs 94.7 ± 1.2%; P = .012) survival rates than NPS group patients. Patients with prior CABG had a lower 1-year survival than NPS group patients (89.0 ± 2.3% vs 94.7 ± 1.2%; P = .018). ConclusionThe PS group had lower 1-year survival and higher intraoperative blood use, postoperative length of ICU and hospital stays, and frequency of reoperation for bleeding than the NPS group. Prior sternotomy increases morbidity and mortality after HTx.

Functional alginate nanoparticles for efficient intracellular release of doxorubicin and hepatoma carcinoma cell targeting therapy

In order to efficiently deliver chemotherapy drugs into hepatoma cells, a pH-sensitive and liver-targeted drug delivery system (glycyrrhetinic acid-modified alginate/doxorubicin-modified alginate complex nanoparticles), termed GA-ALG/DOX-ALG NPs, was prepared. First, GA-ALG and DOX-ALG were synthesized, and then GA-ALG/DOX-ALG NPs self-assembled by mixing GA-ALG and DOX-ALG via dialysis. Properties of pH-sensitivity, biodistribution in mice, and antitumor activity against ectopic hepatoma tumors in the NPs were evaluated. DOX release from GA-ALG/DOX-ALG NPs showed pH-sensitivity; less than 10% of drugs were liberated at pH 7.4 within 9 d while 58.7% of DOX released at pH 4.0. The confocal laser scanning microscope (CLSM) experiment showed that GA-ALG/DOX-ALG NPs can respond to the endosomal/lysosomal environment and had pH-triggered intracellular releasing property. The area under the curve (AUC(0-∞)) and half-life (t(½)) in the liver of GA-ALG/DOX-ALG NPs were 1156.7 μg h/g and 34.3 h, respectively, which was 11.8- and 3.2-fold higher than that of the DOX·HCl group. Furthermore, the inhibition rate of tumor growth was 79.3% after treatment with GA-ALG/DOX-ALG NPs, which was much higher than that of the DOX·HCl (48.5%) and DOX-ALG NPs groups (62.7%). Importantly, no mice died in the GA-ALG/DOX-ALG NPs group, while the mortality rate was 40% in the DOX·HCl group.

The Networked Naturalist: Mobile phone data collection for citizen science and education

Abstract Background/Question/Methods Citizen science projects engage individual volunteers or groups to observe, measure, and contribute data to scientific studies. CENS is building a collection of mobile phone and web-based tools to make the citizen scientist experience more engaging and flexible. CENS is an NSF-funded Information and Technology Center that employs graduate students from Computer Science and Electrical Engineering at UCLA to create open-source software that is environmentally and socially responsible. The overarching goal of the Networked Naturalist project is to enhance participatory learning experiences through citizen science campaigns and help transform the associated learning process. We are collaborating with national field campaigns, such Project BudBurst, and also with the National Park Service to increase participation and retention in citizen scientist campaigns through two main avenues afforded by the use of new technologies: (1) to offer new methods for data collection, primarily using mobile phones, through text, picture, and smart-phone applications, and (2) to provide immediate feedback and automated, engaging analysis of data for informal learning opportunities. We are working to create a robust data collection system to enhance citizen science by ensuring data quality and improving data submission, and to transform participation into an active learning, engaging experience. Results/Conclusions Our experience with volunteers for software testing at UCLA and at the National Park Service has indicated that using mobile phones is an efficient method for collecting environmental and location data and raises public awareness of environmental issues through attracting the attention of the mass media. Individual participation in the What’s Invasive! project by volunteer citizen scientists seems to have been limited by smartphone application availability (iPhone app is currently only available for Santa Monica), although methods for making observations based on text and picture messaging are also available. We have found that running short-term "campaigns" partnered with NPS officials and groups such as schools has been the most effective in not only education-related efforts but also in efficiently identifying and locating species and objects of interest using mobile phones.

Enhancement of latent inhibition by chronic mild stress in rats submitted to emotional response conditioning.

This work evaluated the influence of chronic mild stress on latent inhibition (LI) in rats, using a conditioned emotional response (CER) procedure. Rats were assigned to four groups: a non pre-exposed control group (NPC), a non pre-exposed stressed group (NPS), a preexposed control group (PC), and a pre-exposed stressed group (PS). Stressed animals were submitted to a chronic mild stress (CMS) regimen for three weeks. The off-baseline conditioned emotional response procedure had four phases: licking response training, tone- shock conditioning, retraining, and testing. Conditioning consisted of 2 tone (30 s) and shock (0.5 s) associations. Tone-shock conditioning evidenced by NPS and NPC groups suggests that stress did not interfere with the expression of a conditioned emotional response. Pre-exposure was carried out using 6 tones (30 s) during 2 sessions before conditioning. Prior exposure to the tone resulted in a decrease in learning that was greater in stressed animals. The results indicate an increase in latent inhibition induced by chronic mild stress. Such LI potentiation after CMS may be related to dopamine (DA) neurotransmission reduction in the central nervous system.

Microperfusion techniques for long-term hypothermic preservation

Background The aim of this study was to compare several methods of hypothermic heart preservation. Methods We preserved isolated pig hearts for 24 hours in cold cardioplegia (4° C), using either continuous microperfusion (Group I) or simple storage (Group II), and with a new preservative solution (NPS, groups IA and IIA) vs St. Thomas’ solution (groups IB and IIB). The main characteristics of the NPS include (1) prevention of cell swelling with polyethelene glycol (PEG), (2) low calcium and magnesium, and (3) presence of metabolic substrates, such as glucose, insulin, pyruvate, aspartate, alanyl-glutamine, and membrane stabilization compounds such as ethanol and chlorpromazine. Results The 4 above groups were compared with hearts harvested and immediately reperfused (control group). During preservation, only Group IB showed significant edema (40% ± 8.4% water gain). Adenylate charge was 25% to 50% higher in microperfused Groups IA and IB (0.678 ± 0.049 and 0.795 ± 0.071, respectively) as compared with simple-storage groups IIA and IIB (0.605 ± 0.048 and 0.524 ± 0.160, respectively). Ultrastructural analysis showed that tissue injury occurred mainly in Group IIB (altered mitochondria, chromatin clumping). Functional data showed better recovery of NPS groups as compared with St. Thomas groups: coronary flow was identical in Group IB and control (57.8 ± 22 and 56.6 ± 14 ml/min/100 g, respectively), and in IA > IB ( p < 0.001) and IIA > IIB ( p < 0.01); the rate pressure products were higher in NPS groups compared with St. Thomas groups (IA > IB, p < 0.01); IIA > IIB, p < 0.05). Conclusions The microperfusion method associated with the NPS provides excellent protection in long-term hypothermic heart preservation.

Exogenous surfactant improves lung compliance and oxygenation in adult rats with meconium aspiration

We studied the effects of exogenous surfactant on lung function and morphology in an adult rat model of severe meconium aspiration syndrome. Animals ventilated with 100% oxygen received 4-6 ml of human meconium (25 mg/ml) intratracheally. After 30 min, lung-thorax compliance had decreased by > 30% and arterial PO2 was < 10 kPa. Animals were then treated with no material (MECO group), 0.9% NaCl (MECO-saline group), natural porcine surfactant (NPS group) at a dose of 100 mg/kg, or modified porcine surfactant at a dose of either 100 (MPS100 group) or 200 mg/kg (MPS200 group) and were ventilated for another 180 min. Immediate and sustained improvement of arterial PO2 and compliance was observed in the MPS200 group, whereas the MPS100 and NPS groups showed less pronounced effects. There was a significant improvement of quasi-static lung volumes at maximum insufflation pressure and during deflation in the MPS200, MPS100, and NPS groups. Recordings with Wilhelmy balance showed that minimum surface tension of bronchoalveolar lavage fluid from animals receiving either type or dose of surfactant was significantly lower than in the MECO and MECO-saline groups. Meconium aspiration induced diffuse and prominent atelectasis, intra-alveolar edema, and hyaline membranes. These morphological abnormalities were reversed by exogenous surfactant, especially by the high-dose regimen.

Synthesis and study of intramolecularly-quenched fluorogenic substrates containing aminocoumarin or aminoquinolinone-type fluorophores

The amines 7-amino-4-methylcoumarin (AMec)(1), 7-amino-4-methyl-2-quinolinone (AMeq)(2) and 3-aminocoumarin (Ac)(3) have been used as fluorophores (H–F) and the aromatic systems 2,4-dinitrophenyl (Dnp), 2,4,6-trinitrophenyl (Tnp), 2-nitrophenylsulphenyl (Nps) and 3,5-dinitrobenzoyl (DnBz) have been used as quenchers (Q) in the synthesis of twelve intramolecularly-quenched fluorogenic substrates of general structure Q–Gly–Phe–F. The study of the fluorescence properties of the substrates synthesized shows that efficient quenching of fluorescence is observed in all cases. The Dnp, Nps and Tnp groups show a higher quenching efficiency and the combination of the Dnp group with the fluorophore Ac gives the best result (99% quenching). The substrates synthesized can be used for the direct specific determination of enzymes which hydrolyse the peptide chain at any point between the interacting groups by measuring the increase in fluorescence.

Coupling in the absence of tertiary amines.

In order to avoid base catalyzed side reactions during coupling, attempts were made to render superfluous the addition of tertiary amines to the reaction mixture. Weak acids were applied for the removal of acid labile protecting groups. Acetic acid and other carboxylic acids were considered unsuitable for this purpose coupling step. Pentachlorophenol and 2,4-dinitrophenol cleaved the Bpoc, Nps and Trt groups but more practical rates were reached with solutions of 1-hydroxybenzotriazole (HOBt) in trifluoroethanol, in acetic acid, or in a mixture of phenol and p-cresol. In addition to acidolysis, HOBt salts of amino components could also be obtained through hydrogenolysis of the Z group or thiolysis of the Nps group in the presence of HOBt, or by the displacement of acetic acid from acetate salts with HOBt. Acylation of HOBt salts of amino components with symmetrical or mixed anhydrides or with active esters did not require the addition of tertiary amine.