Biochemical evaluation of the anticancer potential of the polyamine-based nanocarrier Nano11047

PubMed Central

Ferrari, Elena; Xie, Ying; Yu, Fei; Marton, Laurence J.; Oupicky, David; Casero, Robert A.

2017-01-01

Synthesizing polycationic polymers directly from existing drugs overcomes the drug-loading limitations often associated with pharmacologically inert nanocarriers. We recently described nanocarriers formed from a first-generation polyamine analogue, bis(ethyl)norspermine (BENSpm), that could simultaneously target polyamine metabolism while delivering therapeutic nucleic acids. In the current study, we describe the synthesis and evaluation of self-immolative nanocarriers derived from the second-generation polyamine analogue PG-11047. Polyamines are absolutely essential for proliferation and their metabolism is frequently dysregulated in cancer. Through its effects on polyamine metabolism, PG-11047 effectively inhibits tumor growth in cancer cell lines of multiple origins as well as in human tumor mouse xenografts. Promising clinical trials have been completed verifying the safety and tolerance of this rotationally restricted polyamine analogue. We therefore used PG-11047 as the basis for Nano11047, a biodegradable, prodrug nanocarrier capable of targeting polyamine metabolism. Following exposure of lung cancer cell lines to Nano11047, uptake and intracellular degradation into the parent compound PG-11047 was observed. The release of PG-11047 highly induced the polyamine catabolic enzyme activities of spermidine/spermine N1-acetyltransferase (SSAT) and spermine oxidase (SMOX). By contrast, the activity of ornithine decarboxylase (ODC), a rate-limiting enzyme in polyamine biosynthesis and a putative oncogene, was decreased. Consequently, intracellular levels of the natural polyamines were depleted concurrent with tumor cell growth inhibition. This availability of Nano11047 as a novel drug form and potential nucleic acid delivery vector will potentially benefit and encourage future clinical studies. PMID:28423064

Biochemical evaluation of the anticancer potential of the polyamine-based nanocarrier Nano11047.

PubMed

Murray-Stewart, Tracy; Ferrari, Elena; Xie, Ying; Yu, Fei; Marton, Laurence J; Oupicky, David; Casero, Robert A

2017-01-01

Synthesizing polycationic polymers directly from existing drugs overcomes the drug-loading limitations often associated with pharmacologically inert nanocarriers. We recently described nanocarriers formed from a first-generation polyamine analogue, bis(ethyl)norspermine (BENSpm), that could simultaneously target polyamine metabolism while delivering therapeutic nucleic acids. In the current study, we describe the synthesis and evaluation of self-immolative nanocarriers derived from the second-generation polyamine analogue PG-11047. Polyamines are absolutely essential for proliferation and their metabolism is frequently dysregulated in cancer. Through its effects on polyamine metabolism, PG-11047 effectively inhibits tumor growth in cancer cell lines of multiple origins as well as in human tumor mouse xenografts. Promising clinical trials have been completed verifying the safety and tolerance of this rotationally restricted polyamine analogue. We therefore used PG-11047 as the basis for Nano11047, a biodegradable, prodrug nanocarrier capable of targeting polyamine metabolism. Following exposure of lung cancer cell lines to Nano11047, uptake and intracellular degradation into the parent compound PG-11047 was observed. The release of PG-11047 highly induced the polyamine catabolic enzyme activities of spermidine/spermine N1-acetyltransferase (SSAT) and spermine oxidase (SMOX). By contrast, the activity of ornithine decarboxylase (ODC), a rate-limiting enzyme in polyamine biosynthesis and a putative oncogene, was decreased. Consequently, intracellular levels of the natural polyamines were depleted concurrent with tumor cell growth inhibition. This availability of Nano11047 as a novel drug form and potential nucleic acid delivery vector will potentially benefit and encourage future clinical studies.

The potential of magneto-electric nanocarriers for drug delivery

PubMed Central

Kaushik, Ajeet; Jayant, Rahul Dev; Sagar, Vidya; Nair, Madhavan

2015-01-01

Introduction The development and design of personalized nanomedicine for better health quality is receiving great attention. In order to deliver and release a therapeutic concentration at the target site, novel nanocarriers (NCs) were designed, for example, magneto-electric (ME) which possess ideal properties of high drug loading, site-specificity and precise on-demand controlled drug delivery. Areas covered This review explores the potential of ME-NCs for on-demand and site-specific drug delivery and release for personalized therapeutics. The main features including effect of magnetism, improvement in drug loading, drug transport across blood-brain barriers and on-demand controlled release are also discussed. The future directions and possible impacts on upcoming nanomedicine are highlighted. Expert opinion Numerous reports suggest that there is an urgent need to explore novel NC formulations for safe and targeted drug delivery and release at specific disease sites. The challenges of formulation lie in the development of NCs that improve biocompatibility and surface modifications for optimum drug loading/preservation/transmigration and tailoring of electrical–magnetic properties for on-demand drug release. Thus, the development of novel NCs is anticipated to overcome the problems of targeted delivery of therapeutic agents with desired precision that may lead to better patient compliance. PMID:24986772

Highly lipophilic pluronics-conjugated polyamidoamine dendrimer nanocarriers as potential delivery system for hydrophobic drugs.

PubMed

Nguyen, Thi Tram Chau; Nguyen, Cuu Khoa; Nguyen, Thi Hiep; Tran, Ngoc Quyen

2017-01-01

In the study, four kinds of pluronics (P123, F68, F127 and F108) with varying hydrophilic-lipophilic balance (HLB) values were modified and conjugated on 4th generation of polyamidoamine dendrimer (PAMAM). The obtained results from FT-IR, 1 H NMR and GPC showed that the pluronics effectively conjugated on the dendrimer. The molecular weight of four PAMAM G4.0-Pluronics and its morphologies are in range of 200.15-377.14kDa and around 60-180nm in diameter by TEM, respectively. Loading efficiency and release of hydrophobic fluorouracil (5-FU) anticancer drug were evaluated by HPLC; Interesting that the dendrimer nanocarrier was conjugated with the highly lipophilic pluronic P123 (G4.0-P123) exhibiting a higher drug loading efficiency (up to 76.25%) in comparison with another pluronics. Live/dead fibroblast cell staining assay mentioned that all conjugated nanocarriers are highly biocompatible. The drug-loaded nanocarriers also indicated a highly anti-proliferative activity against MCF-7 breast cancer cell. The obtained results demonstrated a great potential of the highly lipophilic pluronics-conjugated nanocarriers in hydrophobic drugs delivery for biomedical applications. Copyright © 2016 Elsevier B.V. All rights reserved.

Nanocarriers for the treatment of glioblastoma multiforme: Current state-of-the-art.

PubMed

Karim, Reatul; Palazzo, Claudio; Evrard, Brigitte; Piel, Geraldine

2016-04-10

Glioblastoma multiforme, a grade IV glioma, is the most frequently occurring and invasive primary tumor of the central nervous system, which causes about 4% of cancer-associated-deaths, making it one of the most fatal cancers. With present treatments, using state-of-the-art technologies, the median survival is about 14 months and 2 year survival rate is merely 3-5%. Hence, novel therapeutic approaches are urgently necessary. However, most drug molecules are not able to cross the blood-brain barrier, which is one of the major difficulties in glioblastoma treatment. This review describes the features of blood-brain barrier, and its anatomical changes with different stages of tumor growth. Moreover, various strategies to improve brain drug delivery i.e. tight junction opening, chemical modification of the drug, efflux transporter inhibition, convection-enhanced delivery, craniotomy-based drug delivery and drug delivery nanosystems are discussed. Nanocarriers are one of the highly potential drug transport systems that have gained huge research focus over the last few decades for site specific drug delivery, including drug delivery to the brain. Properly designed nanocolloids are capable to cross the blood-brain barrier and specifically deliver the drug in the brain tumor tissue. They can carry both hydrophilic and hydrophobic drugs, protect them from degradation, release the drug for sustained period, significantly improve the plasma circulation half-life and reduce toxic effects. Among various nanocarriers, liposomes, polymeric nanoparticles and lipid nanocapsules are the most widely studied, and are discussed in this review. For each type of nanocarrier, a general discussion describing their composition, characteristics, types and various uses is followed by their specific application to glioblastoma treatment. Moreover, some of the main challenges regarding toxicity and standardized evaluation techniques are narrated in brief. Copyright © 2016 Elsevier B.V. All

Development of coated liposomes loaded with ghrelin for nose-to-brain delivery for the treatment of cachexia.

PubMed

Salade, Laurent; Wauthoz, Nathalie; Deleu, Magali; Vermeersch, Marjorie; De Vriese, Carine; Amighi, Karim; Goole, Jonathan

2017-01-01

The aim of the present study was to develop a ghrelin-containing formulation based on liposomes coated with chitosan intended for nose-brain delivery for the treatment of cachexia. Among the three types of liposomes developed, anionic liposomes provided the best results in terms of encapsulation efficiency (56%) and enzymatic protection against trypsin (20.6% vs 0% for ghrelin alone) and carboxylesterase (81.6% vs 17.2% for ghrelin alone). Ghrelin presented both electrostatic and hydrophobic interactions with the anionic lipid bilayer, as demonstrated by isothermal titration calorimetry. Then, anionic liposomes were coated with N -(2-hydroxy) propyl-3-trimethyl ammonium chitosan chloride. The coating involved a size increment from 146.9±2.7 to 194±6.1 nm, for uncoated and coated liposomes, respectively. The ζ-potential was similarly increased from -0.3±1.2 mV to 6±0.4 mV before and after coating, respectively. Chitosan provided mucoadhesion, with an increase in mucin adsorption of 22.9%. Enhancement of permeation through the Calu3 epithelial monolayer was also observed with 10.8% of ghrelin recovered in the basal compartment in comparison to 0% for ghrelin alone. Finally, aerosols generated from two nasal devices (VP3 and SP270) intended for aqueous dispersion were characterized with either coated or uncoated liposomes. Contrarily to the SP270 device, VP3 device showed minor changes between coated and uncoated liposome aerosols, as shown by their median volume diameters of 38.4±5.76 and 37.6±5.74 µm, respectively. Overall, the results obtained in this study show that the developed formulation delivered by the VP3 device can be considered as a potential candidate for nose-brain delivery of ghrelin.

Depletion of liver glutathione levels in rats: a potential confound of nose-only inhalation.

PubMed

Fechter, Laurence D; Nelson-Miller, Alisa; Gearhart, Caroline

2008-07-01

Nose-only inhalation exposure chambers offer key advantages to whole-body systems, particularly when aerosol or mixed aerosol-vapor exposures are used. Specifically, nose-only chambers provide enhanced control over the route of exposure and dose by minimizing the deposition of particles either on the subjects skin/fur or on surfaces of a whole-body exposure system. In the current series of experiments, liver, brain, and lung total glutathione (GSH) levels were assessed following either nose-only or whole-body exposures to either jet fuel or to clean, filtered air. The data were compared to untreated control subjects. Acute nose-only inhalation exposures of rats resulted in a significant depletion of liver GSH levels both in subjects that were exposed to clean, filtered air as well as those exposed to JP-8 jet fuel and to a synthetic jet fuel. Glutathione levels were not altered in lung or brain tissue. Whole-body inhalation exposure had no effect on GSH levels in any tissue for any of the treatment groups. A second experiment demonstrated that the loss of GSH did not occur if rats were anaesthetized prior to and during nose-only exposure to clean, filtered air or to mixed hydrocarbons. These data appear to be consistent with studies demonstrating depletion in liver GSH levels among rats subjected to restraint stress. Finally, the depletion of GSH that was observed in liver following a single acute exposure was reduced following five daily exposures to clean, filtered air, suggesting the possibility of habituation to restraint in the nose-only exposure chamber. The finding that placement in a nose-only exposure chamber per se yields liver GSH depletion raises the possibility of an interaction between this mode of toxicant exposure and the toxicological effects of certain inhaled test substances.

Magnetically guided central nervous system delivery and toxicity evaluation of magneto-electric nanocarriers.

PubMed

Kaushik, Ajeet; Jayant, Rahul D; Nikkhah-Moshaie, Roozbeh; Bhardwaj, Vinay; Roy, Upal; Huang, Zaohua; Ruiz, Ariel; Yndart, Adriana; Atluri, Venkata; El-Hage, Nazira; Khalili, Kamel; Nair, Madhavan

2016-05-04

Least component-based delivery of drug-tagged-nanocarriers across blood-brain-barriers (BBB) will allow site-specific and on-demand release of therapeutics to prevent CNS diseases. We developed a non-invasive magnetically guided delivery of magneto-electric nanocarriers (MENCs), ~20 nm, 10 mg/kg, across BBB in C57Bl/J mice. Delivered MENCs were uniformly distributed inside the brain, and were non-toxic to brain and other major organs, such as kidney, lung, liver, and spleen, and did not affect hepatic, kidney and neurobehavioral functioning.

Magnetically guided central nervous system delivery and toxicity evaluation of magneto-electric nanocarriers

PubMed Central

Kaushik, Ajeet; Jayant, Rahul D.; Nikkhah-Moshaie, Roozbeh; Bhardwaj, Vinay; Roy, Upal; Huang, Zaohua; Ruiz, Ariel; Yndart, Adriana; Atluri, Venkata; El-Hage, Nazira; Khalili, Kamel; Nair, Madhavan

2016-01-01

Least component-based delivery of drug-tagged-nanocarriers across blood-brain-barriers (BBB) will allow site-specific and on-demand release of therapeutics to prevent CNS diseases. We developed a non-invasive magnetically guided delivery of magneto-electric nanocarriers (MENCs), ~20 nm, 10 mg/kg, across BBB in C57Bl/J mice. Delivered MENCs were uniformly distributed inside the brain, and were non-toxic to brain and other major organs, such as kidney, lung, liver, and spleen, and did not affect hepatic, kidney and neurobehavioral functioning. PMID:27143580

Using Electronic Noses to Detect Tumors During Neurosurgery

NASA Technical Reports Server (NTRS)

Homer, Margie L.; Ryan, Margaret A.; Lara, Liana M.; Kateb, Babak; Chen, Mike

2008-01-01

It has been proposed to develop special-purpose electronic noses and algorithms for processing the digitized outputs of the electronic noses for determining whether tissue exposed during neurosurgery is cancerous. At present, visual inspection by a surgeon is the only available intraoperative technique for detecting cancerous tissue. Implementation of the proposal would help to satisfy a desire, expressed by some neurosurgeons, for an intraoperative technique for determining whether all of a brain tumor has been removed. The electronic-nose technique could complement multimodal imaging techniques, which have also been proposed as means of detecting cancerous tissue. There are also other potential applications of the electronic-nose technique in general diagnosis of abnormal tissue. In preliminary experiments performed to assess the viability of the proposal, the problem of distinguishing between different types of cultured cells was substituted for the problem of distinguishing between normal and abnormal specimens of the same type of tissue. The figure presents data from one experiment, illustrating differences between patterns that could be used to distinguish between two types of cultured cancer cells. Further development can be expected to include studies directed toward answering questions concerning not only the possibility of distinguishing among various types of normal and abnormal tissue but also distinguishing between tissues of interest and other odorous substances that may be present in medical settings.

A novel LDL-mimic nanocarrier for the targeted delivery of curcumin into the brain to treat Alzheimer's disease.

PubMed

Meng, Fanfei; Asghar, Sajid; Gao, Shiya; Su, Zhigui; Song, Jue; Huo, Meirong; Meng, Weidong; Ping, Qineng; Xiao, Yanyu

2015-10-01

In this study, a novel low density lipoprotein (LDL)-mimic nanostructured lipid carrier (NLC) modified with lactoferrin (Lf) and loaded with curcumin (Cur) was designed for brain-targeted delivery, and its effect on controlling the progression of Alzheimer's disease (AD) in rats was evaluated. NLC with the composition resembling the lipid portion of LDL was prepared by using solvent evaporation method. Lf was adsorbed onto the surface of NLC via electrostatic interaction to yield Lf modified-NLC (Lf-mNLC) as the LDL-mimic nanocarrier. In order to make sure more Lf was adsorbed on the surface of NLC, negatively charged carboxylated polyethylene glycol (100) monostearate (S100-COOH) was synthesized and anchored into NLC. Different levels of S100-COOH (0-0.02 mmol) and Lf modified NLC (0.5-2.5 mg/mL of Lf solution) were prepared and characterized. The uptake and potential cytotoxicities of different preparations were investigated in the brain capillary endothelial cells (BCECs). An AD model of rats was employed to evaluate the therapeutic effects of Lf-mNLC. The results indicate that Lf-mNLC with a high level of Lf showed the maximum uptake in BCECs (1.39 folds greater than NLC) as cellular uptake of Lf-mNLC by BCECs was found to be mediated by the Lf receptor. FRET studies showed Cur still wrapped inside NLC after uptake by BCECs, demonstrating stability of the carrier as it moved across the BBB. Ex vivo imaging studies exposed Lf-mNLC could effectively permeate BBB and preferentially accumulate in the brain (2.78 times greater than NLC). Histopathological evaluation confirmed superior efficacy of Lf-mNLC in controlling the damage associated with AD. In conclusion, Lf-mNLC is a promising drug delivery system for targeting therapy of brain disease. Copyright © 2015 Elsevier B.V. All rights reserved.

Solid lipid nanoparticles for nose to brain delivery of haloperidol: in vitro drug release and pharmacokinetics evaluation

PubMed Central

Yasir, Mohd; Sara, Udai Vir Singh

2014-01-01

In the present study, haloperidol (HP)-loaded solid lipid nanoparticles (SLNs) were prepared to enhance the uptake of HP to brain via intranasal (i.n.) delivery. SLNs were prepared by a modified emulsification–diffusion technique and evaluated for particle size, zeta potential, drug entrapment efficiency, in vitro drug release, and stability. All parameters were found to be in an acceptable range. In vitro drug release was found to be 94.16±4.78% after 24 h and was fitted to the Higuchi model with a very high correlation coefficient (R2=0.9941). Pharmacokinetics studies were performed on albino Wistar rats and the concentration of HP in brain and blood was measured by high performance liquid chromatography. The brain/blood ratio at 0.5 h for HP-SLNs i.n., HP sol. i.n. and HP sol. i.v. was 1.61, 0.17 and 0.031, respectively, indicating direct nose-to-brain transport, bypassing the blood–brain barrier. The maximum concentration (Cmax) in brain achieved from i.n. administration of HP-SLNs (329.17±20.89 ng/mL, Tmax 2 h) was significantly higher than that achieved after i.v. (76.95±7.62 ng/mL, Tmax 1 h), and i.n. (90.13±6.28 ng/mL, Tmax 2 h) administration of HP sol. The highest drug-targeting efficiency (2362.43%) and direct transport percentage (95.77%) was found with HP-SLNs as compared to the other formulations. Higher DTE (%) and DTP (%) suggest that HP-SLNs have better brain targeting efficiency as compared to other formulations. PMID:26579417

Nose-to-brain transport of melatonin from polymer gel suspensions: a microdialysis study in rats.

PubMed

Jayachandra Babu, R; Dayal, Pankaj Patrick; Pawar, Kasturi; Singh, Mandip

2011-11-01

Exogenous melatonin (MT) has significant neuroprotective roles in Alzheimer's and Parkinson's diseases. This study investigates the delivery MT to brain via nasal route as a polymeric gel suspension using central brain microdialysis in anesthetized rats. Micronized MT suspensions using polymers [carbopol, carboxymethyl cellulose (CMC)] and polyethylene glycol 400 (PEG400) were prepared and characterized for nasal administration. In vitro permeation of the formulations was measured across a three-dimensional tissue culture model EpiAirway(™). The central brain delivery into olfactory bulb of nasally administered MT gel suspensions was studied using brain microdialysis in male Wistar rats. The MT content of microdialysis samples was analyzed by high performance liquid chromatography (HPLC) using electrochemical detection. The nose-to-brain delivery of MT formulations was compared with intravenously administered MT solution. MT suspensions in carbopol and CMC vehicles have shown significantly higher permeability across Epiairway(™) as compared to control, PEG400 (P < 0.05). The brain (olfactory bulb) levels of MT after intranasal administration were 9.22, 6.77 and 4.04-fold higher for carbopol, CMC and PEG400, respectively, than that of intravenous MT in rats. In conclusion, microdialysis studies demonstrated increased brain levels of MT via nasal administration in rats.

Nose-to-brain transport of melatonin from polymer gel suspensions: a microdialysis study in rats

PubMed Central

Babu, R. Jayachandra; Dayal, Pankaj Patrick; Pawar, Kasturi; Singh, Mandip

2012-01-01

Purpose Exogenous melatonin (MT) has significant neuroprotective roles in Alzheimer’s and Parkinson’s diseases. This study investigates the delivery MT to brain via nasal route as a polymeric gel suspension using central brain microdialysis in anesthetized rats. Methods Micronized MT suspensions using polymers [carbopol, carboxymethyl cellulose (CMC)] and polyethylene glycol 400 (PEG400) were prepared and characterized for nasal administration. In vitro permeation of the formulations was measured across a three-dimensional tissue culture model EpiAirway™. The central brain delivery into olfactory bulb of nasally administered MT gel suspensions was studied using brain microdialysis in male Wistar rats. The MT content of microdialysis samples was analyzed by high performance liquid chromatography (HPLC) using electrochemical detection. The nose-to-brain delivery of MT formulations was compared with intravenously administered MT solution. Results MT suspensions in carbopol and CMC vehicles have shown significantly higher permeability across Epiairway™ as compared to control, PEG400 (P < 0.05). The brain (olfactory bulb) levels of MT after intranasal administration were 9.22, 6.77 and 4.04-fold higher for carbopol, CMC and PEG400, respectively, than that of intravenous MT in rats. In conclusion, microdialysis studies demonstrated increased brain levels of MT via nasal administration in rats. PMID:21428693

Decreased circulation time offsets increased efficacy of PEGylated nanocarriers targeting folate receptors of glioma

NASA Astrophysics Data System (ADS)

McNeeley, Kathleen M.; Annapragada, Ananth; Bellamkonda, Ravi V.

2007-09-01

Liposomal and other nanocarrier based drug delivery vehicles can localize to tumours through passive and/or active targeting. Passively targeted liposomal nanocarriers accumulate in tumours via 'leaky' vasculature through the enhanced permeability and retention (EPR) effect. Passive accumulation depends upon the circulation time and the degree of tumour vessel 'leakiness'. After extravasation, actively targeted liposomal nanocarriers efficiently deliver their payload by receptor-mediated uptake. However, incorporation of targeting moieties can compromise circulation time in the blood due to recognition and clearance by the reticuloendothelial system, decreasing passive accumulation. Here, we compare the efficacy of passively targeted doxorubicin-loaded PEGylated liposomal nanocarriers to that of actively targeted liposomal nanocarriers in a rat 9L brain tumour model. Although folate receptor (FR)-targeted liposomal nanocarriers had significantly reduced blood circulation time compared to PEGylated liposomal nanocarriers; intratumoural drug concentrations both at 20 and 50 h after administration were equal for both treatments. Both treatments significantly increased tumour inoculated animal survival by 60-80% compared to non-treated controls, but no difference in survival was observed between FR-targeted and passively targeted nanocarriers. Therefore, alternate approaches allowing for active targeting without compromising circulation time may be important for fully realizing the benefits of receptor-mediated active targeting of gliomas.

Phosphatidylserine-Targeted Nanotheranostics for Brain Tumor Imaging and Therapeutic Potential

PubMed Central

Wang, Lulu; Habib, Amyn A.; Mintz, Akiva; Li, King C.; Zhao, Dawen

2017-01-01

Phosphatidylserine (PS), the most abundant anionic phospholipid in cell membrane, is strictly confined to the inner leaflet in normal cells. However, this PS asymmetry is found disruptive in many tumor vascular endothelial cells. We discuss the underlying mechanisms for PS asymmetry maintenance in normal cells and its loss in tumor cells. The specificity of PS exposure in tumor vasculature but not normal blood vessels may establish it a useful biomarker for cancer molecular imaging. Indeed, utilizing PS-targeting antibodies, multiple imaging probes have been developed and multimodal imaging data have shown their high tumor-selective targeting in various cancers. There is a critical need for improved diagnosis and therapy for brain tumors. We have recently established PS-targeted nanoplatforms, aiming to enhance delivery of imaging contrast agents across the blood–brain barrier to facilitate imaging of brain tumors. Advantages of using the nanodelivery system, in particular, lipid-based nanocarriers, are discussed here. We also describe our recent research interest in developing PS-targeted nanotheranostics for potential image-guided drug delivery to treat brain tumors. PMID:28654387

Phosphatidylserine-Targeted Nanotheranostics for Brain Tumor Imaging and Therapeutic Potential.

PubMed

Wang, Lulu; Habib, Amyn A; Mintz, Akiva; Li, King C; Zhao, Dawen

2017-01-01

Phosphatidylserine (PS), the most abundant anionic phospholipid in cell membrane, is strictly confined to the inner leaflet in normal cells. However, this PS asymmetry is found disruptive in many tumor vascular endothelial cells. We discuss the underlying mechanisms for PS asymmetry maintenance in normal cells and its loss in tumor cells. The specificity of PS exposure in tumor vasculature but not normal blood vessels may establish it a useful biomarker for cancer molecular imaging. Indeed, utilizing PS-targeting antibodies, multiple imaging probes have been developed and multimodal imaging data have shown their high tumor-selective targeting in various cancers. There is a critical need for improved diagnosis and therapy for brain tumors. We have recently established PS-targeted nanoplatforms, aiming to enhance delivery of imaging contrast agents across the blood-brain barrier to facilitate imaging of brain tumors. Advantages of using the nanodelivery system, in particular, lipid-based nanocarriers, are discussed here. We also describe our recent research interest in developing PS-targeted nanotheranostics for potential image-guided drug delivery to treat brain tumors.

Recent advances in topical delivery of proteins and peptides mediated by soft matter nanocarriers.

PubMed

Witting, Madeleine; Obst, Katja; Friess, Wolfgang; Hedtrich, Sarah

2015-11-01

Proteins and peptides are increasingly important therapeutics for the treatment of severe and complex diseases like cancer or autoimmune diseases due to their high specificity and potency. Their unique structure and labile physicochemical properties, however, require special attention in the production and formulation process as well as during administration. Aside from conventional systemic injections, the topical application of proteins and peptides is an appealing alternative due to its non-invasive nature and thus high acceptance by patients. For this approach, soft matter nanocarriers are interesting delivery systems which offer beneficial properties such as high biocompatibility, easiness of modifications, as well as targeted drug delivery and release. This review aims to highlight and discuss technological developments in the field of soft matter nanocarriers for the delivery of proteins and peptides via the skin, the eye, the nose, and the lung, and to provide insights in advantages, limitations, and practicability of recent advances. Copyright © 2015 Elsevier Inc. All rights reserved.

Lecithin-based novel cationic nanocarriers (LeciPlex) I: fabrication, characterization and evaluation.

PubMed

Date, Abhijit A; Srivastava, Deepika; Nagarsenker, Mangal S; Mulherkar, Rita; Panicker, Lata; Aswal, Vinod; Hassan, Puthusserickal A; Steiniger, Frank; Thamm, Jana; Fahr, Alfred

2011-10-01

In the present investigation, the feasibility of fabricating novel self-assembled cationic nanocarriers (LeciPlex) containing cetyltrimethylammonium bromide (CTAB) or didodecyldimethylammonium bromide (DDAB) and soybean lecithin using pharmaceutically acceptable biocompatible solvents such as 2-Pyrrolidone (Soluphor P) and diethyleneglycol monoethyl ether (Transcutol) was established. The interaction between DDAB/CTAB and soybean lecithin in the nanocarriers was confirmed by differential scanning calorimetry and in vitro antimicrobial studies. The positive charge on the nanocarriers was confirmed by zeta potential analysis. Transmission electron microscopy analysis could not reveal sufficient information regarding the internal structure of the nanocarriers, whereas cryotransmission electron microscopy studies indicated that these novel nanocarriers have unilamellar structure. Small-angle neutron scattering studies confirmed interaction of cationic surfactant (DDAB) and lecithin in the nanocarriers and confirmed the presence of unilamellar nanostructures. Various hydrophobic drugs could be encapsulated in the CTAB/DDAB-based lecithin nanocarriers (CTAB-LeciPlex or DDAB-LeciPlex) irrespective of their difference in log p-values. In vitro antimicrobial studies on triclosan-loaded LeciPlex confirmed entrapment of triclosan in the nanocarriers. The ability of CTAB-LeciPlex and DDAB-LeciPlex to condense plasmid DNA was established using agarose gel electrophoresis. DDAB-LeciPlex could successfully transfect pDNA in HEK-293 cells indicating potential in gene delivery.

Lactoferrin-modified rotigotine nanoparticles for enhanced nose-to-brain delivery: LESA-MS/MS-based drug biodistribution, pharmacodynamics, and neuroprotective effects.

PubMed

Yan, Xiuju; Xu, Lixiao; Bi, Chenchen; Duan, Dongyu; Chu, Liuxiang; Yu, Xin; Wu, Zimei; Wang, Aiping; Sun, Kaoxiang

2018-01-01

Efficient delivery of rotigotine into the brain is crucial for obtaining maximum therapeutic efficacy for Parkinson's disease (PD). Therefore, in the present study, we prepared lactoferrin-modified rotigotine nanoparticles (Lf-R-NPs) and studied their biodistribution, pharmacodynamics, and neuroprotective effects following nose-to-brain delivery in the rat 6-hydroxydopamine model of PD. The biodistribution of rotigotine nanoparticles (R-NPs) and Lf-R-NPs after intranasal administration was assessed by liquid extraction surface analysis coupled with tandem mass spectrometry. Contralateral rotations were quantified to evaluate pharmacodynamics. Tyrosine hydroxylase and dopamine transporter immunohistochemistry were performed to compare the neuroprotective effects of levodopa, R-NPs, and Lf-R-NPs. Liquid extraction surface analysis coupled with tandem mass spectrometry analysis, used to examine rotigotine biodistribution, showed that Lf-R-NPs more efficiently supplied rotigotine to the brain (with a greater sustained amount of the drug delivered to this organ, and with more effective targeting to the striatum) than R-NPs. The pharmacodynamic study revealed a significant difference ( P <0.05) in contralateral rotations between rats treated with Lf-R-NPs and those treated with R-NPs. Furthermore, Lf-R-NPs significantly alleviated nigrostriatal dopaminergic neurodegeneration in the rat model of 6-hydroxydopamine-induced PD. Our findings show that Lf-R-NPs deliver rotigotine more efficiently to the brain, thereby enhancing efficacy. Therefore, Lf-R-NPs might have therapeutic potential for the treatment of PD.

From the Cover: Potentiation of Drug-Induced Phospholipidosis In Vitro through PEGlyated Graphene Oxide as the Nanocarrier.

PubMed

Yang, Liecheng; Zhong, Xiaoyan; Li, Qian; Zhang, Xihui; Wang, Yangyun; Yang, Kai; Zhang, Leshuai W

2017-03-01

Cationic amphiphilic drugs (CADs) are small molecules that can induce phospholipidosis (PLD), causing the intracellular accumulation of phospholipid in the lamellar bodies. Nanotechnology based drug delivery systems have been used widely, while it is unknown if drug-induced PLD (DIP) can be potentiated through drug retention by indigestible nanocarriers. Due to the high drug loading capacity of graphene, we investigated if PEGylated graphene oxide (PEG-GO) loaded with CAD could potentiate DIP. Tamoxifen induced the accumulation of NBD-PE, a fluorescence labeled phospholipid in human hepatoma HepG2 cells, while PEG-GO loaded with tamoxifen (PEG-GO/tamoxifen) further potentiated PLD. PEG-GO/tamoxifen induced more gene expression of PLD marker than tamoxifen alone. PEG-GO enhanced DIP was also observed for other CAD, indicating that nanocarrier potentiated DIP could be universal. More lamellar bodies were observed in PEG-GO/tamoxifen treated cells than tamoxifen alone by transmission electron microscopy. When compared with tamoxifen alone, PEG-GO/tamoxifen showed a delayed but potent PLD. In addition, the retarded PLD recovery by PEG-GO/tamoxifen indicated that the reversibility of DIP was interfered. Confocal microscopy revealed the increased number of lysosomes, greater expression of lysosomal associated membrane protein 2 (LAMP2) (a PLD marker), and an increase in the co-localization between lysosome/LAMP2 and NBD-PE by PEG-GO/tamoxifen rather than tamoxifen alone. Finally, we found that PEG-GO or/and tamoxifen-induced PLD seemed to have no correlation with autophagy. This research suggests pharmaceutical companies and regulatory agencies that if nanoparticles are used as the vectors for drug delivery, the adverse drug effects may be further potentiated probably through the long-term accumulation of nanocarriers. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e

Tweaking Dendrimers and Dendritic Nanoparticles for Controlled Nano-bio Interactions: Potential Nanocarriers for Improved Cancer Targeting

PubMed Central

Bugno, Jason; Hsu, Hao-Jui; Hong, Seungpyo

2016-01-01

Nanoparticles have shown great promise in the treatment of cancer, with a demonstrated potential in targeted drug delivery. Among a myriad of nanocarriers that have been recently developed, dendrimers have attracted a great deal of scientific interests due to their unique chemical and structural properties that allow for precise engineering of their characteristics. Despite this, the clinical translation of dendrimers has been hindered due to their drawbacks, such as scale-up issues, rapid systemic elimination, inefficient tumor accumulation, and limited drug loading. In order to overcome these limitations, a series of reengineered dendrimers have been recently introduced using various approaches, including: i) modifications of structure and surfaces; ii) integration with linear polymers; and iii) hybridization with other types of nanocarriers. Chemical modifications and surface engineering have tailored dendrimers to improve their pharmacokinetics and tissue permeation. Copolymerization of dendritic polymers with linear polymers has resulted in various amphiphilic copolymers with self-assembly capabilities and improved drug loading efficiencies. Hybridization with other nanocarriers integrates advantageous characteristics of both systems, which includes prolonged plasma circulation times and enhanced tumor targeting. This review provides a comprehensive summary of the newly emerging drug delivery systems that involve reengineering of dendrimers in an effort to precisely control their nano-bio interactions, mitigating their inherent weaknesses. PMID:26453160

Sugar-Grafted Cyclodextrin Nanocarrier as a "Trojan Horse" for Potentiating Antibiotic Activity.

PubMed

Li, Min; Neoh, Koon Gee; Xu, Liqun; Yuan, Liang; Leong, David Tai; Kang, En-Tang; Chua, Kim Lee; Hsu, Li Yang

2016-05-01

The use of "Trojan Horse" nanocarriers for antibiotics to enhance the activity of antibiotics against susceptible and resistant bacteria is investigated. Antibiotic carriers (CD-MAN and CD-GLU) are prepared from β-cyclodextrin grafted with sugar molecules (D-mannose and D-glucose, respectively) via azide-alkyne click reaction. The sugar molecules serve as a chemoattractant enticing the bacteria to take in higher amounts of the antibiotic, resulting in rapid killing of the bacteria. Three types of hydrophobic antibiotics, erythromycin, rifampicin and ciprofloxacin, are used as model drugs and loaded into the carriers. The minimum inhibitory concentration of the antibiotics in the CD-MAN-antibiotic and CD-GLU-antibiotic complexes for Gram-negative Escherichia coli, Pseudomonas aeruginosa and Acinetobacter baumannii strains, and a number of Gram-positive Staphylococcus aureus strains, including the methicillin-resistant strains (MRSA), are reduced by a factor ranging from 3 to >100. The CD-MAN-antibiotic complex is also able to prolong the stability of the loaded antibiotic and inhibit development of intrinsic antibiotic resistance in the bacteria. These non-cytotoxic sugar-modfied nanocarriers can potentiate the activity of existing antibiotics, especially against multidrug-resistant bacteria, which is highly advantageous in view of the paucity of new antibiotics in the pipeline.

Smuggling Drugs into the Brain: An Overview of Ligands Targeting Transcytosis for Drug Delivery across the Blood-Brain Barrier.

PubMed

Georgieva, Julia V; Hoekstra, Dick; Zuhorn, Inge S

2014-11-17

The blood-brain barrier acts as a physical barrier that prevents free entry of blood-derived substances, including those intended for therapeutic applications. The development of molecular Trojan horses is a promising drug targeting technology that allows for non-invasive delivery of therapeutics into the brain. This concept relies on the application of natural or genetically engineered proteins or small peptides, capable of specifically ferrying a drug-payload that is either directly coupled or encapsulated in an appropriate nanocarrier, across the blood-brain barrier via receptor-mediated transcytosis. Specifically, in this process the nanocarrier-drug system ("Trojan horse complex") is transported transcellularly across the brain endothelium, from the blood to the brain interface, essentially trailed by a native receptor. Naturally, only certain properties would favor a receptor to serve as a transporter for nanocarriers, coated with appropriate ligands. Here we briefly discuss brain microvascular endothelial receptors that have been explored until now, highlighting molecular features that govern the efficiency of nanocarrier-mediated drug delivery into the brain.

Specific Binding, Uptake, and Transport of ICAM-1-Targeted Nanocarriers Across Endothelial and Subendothelial Cell Components of the Blood-Brain Barrier

PubMed Central

Hsu, Janet; Rappaport, Jeff; Muro, Silvia

2014-01-01

Purpose The blood-brain barrier (BBB) represents a target for therapeutic intervention and an obstacle for brain drug delivery. Targeting endocytic receptors on brain endothelial cells (ECs) helps transporting drugs and carriers into and across this barrier. While most receptors tested are associated with clathrin-mediated pathways, clathrin-independent routes are rather unexplored. We have examined the potential for one of these pathways, cell adhesion molecule (CAM)-mediated endocytosis induced by targeting intercellular adhesion molecule 1 (ICAM-1), to transport drug carriers into and across BBB models. Methods Model polymer nanocarriers (NCs) coated with control IgG or antibodies against ICAM-1 (IgG NCs vs. anti-ICAM NCs; ~250-nm) were incubated with human brain ECs, astrocytes (ACs), or pericytes (PCs) grown as monocultures or bilayered (endothelial+subendothelial) co-cultures. Results ICAM-1 was present and overexpressed in disease-like conditions on ECs and, at a lesser extent, on ACs and PCs which are BBB subendothelial components. Specific targeting and CAM-mediated uptake of anti-ICAM NCs occurred in these cells, although this was greater for ECs. Anti-ICAM NCs were transported across endothelial monolayers and endothelial+subendothelial co-cultures modeling the BBB. Conclusions CAM-mediated transport induced by ICAM-1 targeting operates in endothelial and subendothelial cellular components of the BBB, which may provide an avenue to overcome this barrier. PMID:24558007

Specific binding, uptake, and transport of ICAM-1-targeted nanocarriers across endothelial and subendothelial cell components of the blood-brain barrier.

PubMed

Hsu, Janet; Rappaport, Jeff; Muro, Silvia

2014-07-01

The blood-brain barrier (BBB) represents a target for therapeutic intervention and an obstacle for brain drug delivery. Targeting endocytic receptors on brain endothelial cells (ECs) helps transport drugs and carriers into and across this barrier. While most receptors tested are associated with clathrin-mediated pathways, clathrin-independent routes are rather unexplored. We have examined the potential for one of these pathways, cell adhesion molecule (CAM)-mediated endocytosis induced by targeting intercellular adhesion molecule -1 (ICAM-1), to transport drug carriers into and across BBB models. Model polymer nanocarriers (NCs) coated with control IgG or antibodies against ICAM-1 (IgG NCs vs. anti-ICAM NCs; ~250-nm) were incubated with human brain ECs, astrocytes (ACs), or pericytes (PCs) grown as monocultures or bilayered (endothelial+subendothelial) co-cultures. ICAM-1 was present and overexpressed in disease-like conditions on ECs and, at a lesser extent, on ACs and PCs which are BBB subendothelial components. Specific targeting and CAM-mediated uptake of anti-ICAM NCs occurred in these cells, although this was greater for ECs. Anti-ICAM NCs were transported across endothelial monolayers and endothelial+subendothelial co-cultures modeling the BBB. CAM-mediated transport induced by ICAM-1 targeting operates in endothelial and subendothelial cellular components of the BBB, which may provide an avenue to overcome this barrier.

PSMA-Targeted Theranostic Nanocarrier for Prostate Cancer

PubMed Central

Flores, Orielyz; Santra, Santimukul; Kaittanis, Charalambos; Bassiouni, Rania; Khaled, Amr S; Khaled, Annette R.; Grimm, Jan; Perez, J Manuel

2017-01-01

Herein, we report the use of a theranostic nanocarrier (Folate-HBPE(CT20p)) to deliver a therapeutic peptide to prostate cancer tumors that express PSMA (folate hydrolase 1). The therapeutic peptide (CT20p) targets and inhibits the chaperonin-containing TCP-1 (CCT) protein-folding complex, is selectively cytotoxic to cancer cells, and is non-toxic to normal tissue. With the delivery of CT20p to prostate cancer cells via PSMA, a dual level of cancer specificity is achieved: (1) selective targeting to PSMA-expressing prostate tumors, and (2) specific cytotoxicity to cancer cells with minimal toxicity to normal cells. The PSMA-targeting theranostic nanocarrier can image PSMA-expressing cells and tumors when a near infrared dye is used as cargo. Meanwhile, it can be used to treat PSMA-expressing tumors when a therapeutic, such as the CT20p peptide, is encapsulated within the nanocarrier. Even when these PSMA-targeting nanocarriers are taken up by macrophages, minimal cell death is observed in these cells, in contrast with doxorubicin-based therapeutics that result in significant macrophage death. Incubation of PSMA-expressing prostate cancer cells with the Folate-HBPE(CT20p) nanocarriers induces considerable changes in cell morphology, reduction in the levels of integrin β1, and lower cell adhesion, eventually resulting in cell death. These results are relevant as integrin β1 plays a key role in prostate cancer invasion and metastatic potential. In addition, the use of the developed PSMA-targeting nanocarrier facilitates the selective in vivo delivery of CT20p to PSMA-positive tumor, inducing significant reduction in tumor size. PMID:28744329

Development and characterization of morin hydrate-loaded micellar nanocarriers for the effective management of Alzheimer's disease.

PubMed

Singh, Manpreet; Thakur, Vandana; Deshmukh, Rahul; Sharma, Amit; Rathore, M S; Kumar, Ajay; Mishra, Neeraj

2018-03-01

The aim of this study was to prepare and characterise oral delivery of morin hydrate-loaded micellar nanocarriers using Pluronic P127 and Pluronic F123 for the effective management of Alzheimer's disease. After administration of formulation brain and blood drug concentration were found to be highest for optimised morin hydrate-loaded micellar nanocarriers as compared to plain morin hydrate. Significant (p < 0.05) reduction in assessed pharmacodynamic parameters was observed after administration of morin hydrate-loaded micellar nanocarriers as compared to disease control group. Chronic treatment with morin-loaded micelles significantly increased the memory in AlCl 3 induced Alzheimer's disease in Wistar rats.

Lactoferrin-modified rotigotine nanoparticles for enhanced nose-to-brain delivery: LESA-MS/MS-based drug biodistribution, pharmacodynamics, and neuroprotective effects

PubMed Central

Bi, Chenchen; Duan, Dongyu; Chu, Liuxiang; Yu, Xin; Wu, Zimei; Wang, Aiping; Sun, Kaoxiang

2018-01-01

Introduction Efficient delivery of rotigotine into the brain is crucial for obtaining maximum therapeutic efficacy for Parkinson’s disease (PD). Therefore, in the present study, we prepared lactoferrin-modified rotigotine nanoparticles (Lf-R-NPs) and studied their biodistribution, pharmacodynamics, and neuroprotective effects following nose-to-brain delivery in the rat 6-hydroxydopamine model of PD. Materials and methods The biodistribution of rotigotine nanoparticles (R-NPs) and Lf-R-NPs after intranasal administration was assessed by liquid extraction surface analysis coupled with tandem mass spectrometry. Contralateral rotations were quantified to evaluate pharmacodynamics. Tyrosine hydroxylase and dopamine transporter immunohistochemistry were performed to compare the neuroprotective effects of levodopa, R-NPs, and Lf-R-NPs. Results Liquid extraction surface analysis coupled with tandem mass spectrometry analysis, used to examine rotigotine biodistribution, showed that Lf-R-NPs more efficiently supplied rotigotine to the brain (with a greater sustained amount of the drug delivered to this organ, and with more effective targeting to the striatum) than R-NPs. The pharmacodynamic study revealed a significant difference (P<0.05) in contralateral rotations between rats treated with Lf-R-NPs and those treated with R-NPs. Furthermore, Lf-R-NPs significantly alleviated nigrostriatal dopaminergic neurodegeneration in the rat model of 6-hydroxydopamine-induced PD. Conclusion Our findings show that Lf-R-NPs deliver rotigotine more efficiently to the brain, thereby enhancing efficacy. Therefore, Lf-R-NPs might have therapeutic potential for the treatment of PD. PMID:29391788

Trigeminal pathways deliver a low molecular weight drug from the nose to the brain and orofacial structures.

PubMed

Johnson, Neil J; Hanson, Leah R; Frey, William H

2010-06-07

Intranasal delivery has been shown to noninvasively deliver drugs from the nose to the brain in minutes along the olfactory and trigeminal nerve pathways, bypassing the blood-brain barrier. However, no one has investigated whether nasally applied drugs target orofacial structures, despite high concentrations observed in the trigeminal nerve innervating these tissues. Following intranasal administration of lidocaine to rats, trigeminally innervated structures (teeth, temporomandibular joint (TMJ), and masseter muscle) were found to have up to 20-fold higher tissue concentrations of lidocaine than the brain and blood as measured by ELISA. This concentration difference could allow intranasally administered therapeutics to treat disorders of orofacial structures (i.e., teeth, TMJ, and masseter muscle) without causing unwanted side effects in the brain and the rest of the body. In this study, an intranasally administered infrared dye reached the brain within 10 minutes. Distribution of dye is consistent with dye entering the trigeminal nerve after intranasal administration through three regions with high drug concentrations in the nasal cavity: the middle concha, the maxillary sinus, and the choana. In humans the trigeminal nerve passes through the maxillary sinus to innervate the maxillary teeth. Delivering lidocaine intranasally may provide an effective anesthetic technique for a noninvasive maxillary nerve block. Intranasal delivery could be used to target vaccinations and treat disorders with fewer side effects such as tooth pain, TMJ disorder, trigeminal neuralgia, headache, and brain diseases.

Identifying lipidic emulsomes for improved oxcarbazepine brain targeting: In vitro and rat in vivo studies.

PubMed

El-Zaafarany, Ghada M; Soliman, Mahmoud E; Mansour, Samar; Awad, Gehanne A S

2016-04-30

Lipid-based nanovectors offer effective carriers for brain delivery by improving drug potency and reducing off-target effects. Emulsomes are nano-triglyceride (TG) carriers formed of lipid cores supported by at least one phospholipid (PC) sheath. Due to their surface active properties, PC forms bilayers at the aqueous interface, thereby enabling encapsulated drug to benefit from better bioavailability and stability. Emulsomes of oxcarbazepine (OX) were prepared, aimed to offer nanocarriers for nasal delivery for brain targeting. Different TG cores (Compritol(®), tripalmitin, tristearin and triolein) and soya phosphatidylcholine in different amounts and ratios were used for emulsomal preparation. Particles were modulated to generate nanocarriers with suitable size, charge, encapsulation efficiency and prolonged release. Cytotoxicity and pharmacokinetic studies were also implemented. Nano-spherical OX-emulsomes with maximal encapsulation of 96.75% were generated. Stability studies showed changes within 30.6% and 11.2% in the size and EE% after 3 months. MTT assay proved a decrease in drug toxicity by its encapsulation in emulsomes. Incorporation of OX into emulsomes resulted in stable nanoformulations. Tailoring emulsomes properties by modulating the surface charge and particle size produced a stable system for the lipophilic drug with a prolonged release profile and mean residence time and proved direct nose-to-brain transport in rats. Copyright © 2016 Elsevier B.V. All rights reserved.

Stimuli-responsive chitosan-based nanocarriers for cancer therapy

PubMed Central

Fathi, Marziyeh; Sahandi Zangabad, Parham; Majidi, Sima; Barar, Jaleh; Erfan-Niya, Hamid

2017-01-01

Introduction: Stimuli-responsive nanocarriers offer unique advantages over the traditional drug delivery systems (DDSs) in terms of targeted drug delivery and on-demand release of cargo drug molecules. Of these, chitosan (CS)-based DDSs offer several advantages such as high compatibility with biological settings. Methods: In this study, we surveyed the literature in terms of the stimuli-responsive nanocarriers and discussed the most recent advancements in terms of CS-based nanosystems and their applications in cancer therapy and diagnosis. Results: These advanced DDSs are able to release the entrapped drugs in response to a specific endogenous stimulus (e.g., pH, glutathione concentration or certain enzymes) or exogenous stimulus (e.g., temperature, light, ultrasound, and magnetic field) at the desired time and target site. Dual-responsive nanocarriers by the combination of different stimuli have also been developed as efficient and improved DDSs. Among the stimuli-responsive nanocarriers, CS-based DDSs offer several advantages, including biocompatibility and biodegradability, antibacterial activity, ease of modification and functionalization, and non-immunogenicity. They are as one of the most ideal smart multifunction DDSs. Conclusion: The CS-based stimuli-responsive multifunctional nanosystems (NSs) offer unique potential for the targeted delivery of anticancer agents and provide great potential for on-demand and controlled-release of anticancer agents in response to diverse external/internal stimuli. PMID:29435435

Stimuli-responsive chitosan-based nanocarriers for cancer therapy.

PubMed

Fathi, Marziyeh; Sahandi Zangabad, Parham; Majidi, Sima; Barar, Jaleh; Erfan-Niya, Hamid; Omidi, Yadollah

2017-01-01

Introduction: Stimuli-responsive nanocarriers offer unique advantages over the traditional drug delivery systems (DDSs) in terms of targeted drug delivery and on-demand release of cargo drug molecules. Of these, chitosan (CS)-based DDSs offer several advantages such as high compatibility with biological settings. Methods: In this study, we surveyed the literature in terms of the stimuli-responsive nanocarriers and discussed the most recent advancements in terms of CS-based nanosystems and their applications in cancer therapy and diagnosis. Results: These advanced DDSs are able to release the entrapped drugs in response to a specific endogenous stimulus (e.g., pH, glutathione concentration or certain enzymes) or exogenous stimulus (e.g., temperature, light, ultrasound, and magnetic field) at the desired time and target site. Dual-responsive nanocarriers by the combination of different stimuli have also been developed as efficient and improved DDSs. Among the stimuli-responsive nanocarriers, CS-based DDSs offer several advantages, including biocompatibility and biodegradability, antibacterial activity, ease of modification and functionalization, and non-immunogenicity. They are as one of the most ideal smart multifunction DDSs. Conclusion: The CS-based stimuli-responsive multifunctional nanosystems (NSs) offer unique potential for the targeted delivery of anticancer agents and provide great potential for on-demand and controlled-release of anticancer agents in response to diverse external/internal stimuli.

Formulation of olfactory-targeted microparticles with tamarind seed polysaccharide to improve nose-to-brain transport of drugs.

PubMed

Yarragudi, Sasi B; Richter, Robert; Lee, Helen; Walker, Greg F; Clarkson, Andrew N; Kumar, Haribalan; Rizwan, Shakila B

2017-05-01

Targeted delivery and retention of drug formulations in the olfactory mucosa, the target site for nose-to-brain drug absorption is a major challenge due to the geometrical complexity of the nose and nasal clearance. Recent modelling data indicates that 10μm-sized microparticles show maximum deposition in the olfactory mucosa. In the present study we tested the hypothesis that 10μm-sized mucoadhesive microparticles would preferentially deposit on, and increase retention of drug on, the olfactory mucosa in a novel 3D-printed human nasal-replica cast under simulated breathing. The naturally occurring mucoadhesive polymer, tamarind seed polysaccharide (TSP) was used to formulate the microparticles using a spray drying technique. Physicochemical properties of microparticles such as size, morphology and mucoadhesiveness was investigated using a combination of laser diffraction, electron microscopy and texture-analysis. Furthermore, FITC-dextrans (5-40kDa) were incorporated in TSP-microparticles as model drugs. Size-dependent permeability of the FITC-dextrans was observed ex vivo using porcine nasal mucosa. Using the human nasal-replica cast, greater deposition of 10μm TSP-microparticles in the olfactory region was observed compared to TSP-microparticles 2μm in size. Collectively, these findings support our hypothesis that 10μm-sized mucoadhesive microparticles can achieve selective deposition and retention of drug in the olfactory mucosa. Copyright © 2017 Elsevier Ltd. All rights reserved.

Intranasal delivery of nanoparticle encapsulated tarenflurbil: A potential brain targeting strategy for Alzheimer's disease.

PubMed

Muntimadugu, Eameema; Dhommati, Raju; Jain, Anjali; Challa, Venu Gopala Swami; Shaheen, M; Khan, Wahid

2016-09-20

Poor brain penetration of tarenflurbil (TFB) was one of the major reasons for its failure in phase III clinical trials conducted on Alzheimer's patients. Thus there is a tremendous need of developing efficient delivery systems for TFB. This study was designed with the aim of improving drug delivery to brain through intranasally delivered nanocarriers. TFB was loaded into two different nanocarriers i.e., poly (lactide-co-glycolide) nanoparticles (TFB-NPs) and solid lipid nanoparticles (TFB-SLNs). Particle size of both the nanocarriers (<200nm) as determined by dynamic light scattering technique and transmission electron microscopy, assured transcellular transport across olfactory axons whose diameter was ≈200nm and then paving a direct path to brain. TFB-NPs and TFB-SLNs resulted in 64.11±2.21% and 57.81±5.32% entrapment efficiencies respectively which again asserted protection of drug from chemical and biological degradation in nasal cavity. In vitro release studies proved the sustained release of TFB from TFB-NPs and TFB-SLNs in comparison with pure drug, indicating prolonged residence times of drug at targeting site. Pharmacokinetics suggested improved circulation behavior of nanoparticles and the absolute bioavailabilities followed this order: TFB-NPs (i.n.)>TFB-SLNs (i.n.)>TFB solution (i.n.)>TFB suspension (oral). Brain targeting efficiency was determined in terms of %drug targeting efficiency (%DTE) and drug transport percentage (DTP). The higher %DTE (287.24) and DTP (65.18) were observed for TFB-NPs followed by TFB-SLNs (%DTE: 183.15 and DTP: 45.41) among all other tested groups. These encouraging results proved that therapeutic concentrations of TFB could be transported directly to brain via olfactory pathway after intranasal administration of polymeric and lipidic nanoparticles. Copyright © 2016 Elsevier B.V. All rights reserved.

Hydrodynamic interactions for complex-shaped nanocarriers in targeted drug delivery

NASA Astrophysics Data System (ADS)

Wang, Yaohong; Eckmann, David; Radhakrishnan, Ravi; Ayyaswamy, Portonovo

2014-11-01

Nanocarrier motion in a blood vessel involves hydrodynamic and Brownian interactions, which collectively dictate the efficacy in targeted drug delivery. The shape of nanocarriers plays a crucial role in drug delivery. In order to quantify the flow and association properties of elliptical nanoparticles, we have developed an arbitrary Lagrangian-Eulerian framework with capabilities to simulate the hydrodynamic motion of nanoparticles of arbitrary shapes. We introduce the quaternions for rotational motion, and two collision models, namely, (a) an impulse-based model for wall-particle collision, and (b) the short-range repulsive Gay-Berne potential for particle-particle collision. We also study the red blood cell and nanocarrier (such as ellipsoid) interactions. We compare our results with those obtained for a hard sphere model for both RBCs and nanocarriers. Supported by NIH through grant U01-EB016027.

Rivastigmine-loaded in situ gelling nanostructured lipid carriers for nose to brain delivery.

PubMed

Wavikar, Preeti R; Vavia, Pradeep R

2015-01-01

In the current research work, rivastigmine (RV)-loaded in situ gelling nanostructured lipid carriers (NLCs) were developed for nose to brain delivery. NLCs were fabricated by ethanol injection method using glyceryl monosterate, Capmul MCM C8, Lecithin and Tween 80. NLCs showed average particle size of 123.2 ± 2.3 nm with entrapment efficiency of 68.34 ± 3.4%. DSC, XRD and IR studies showed complete amorphization and incorporation of the drug into nanoparticles. NLCs were incorporated into an in situ gelling system using 0.8% gellan gum and 15% Lutrol F 127. RV in situ gel showed excellent elasticity, rheology, mucoadhesion and adhesiveness to facilitate its adhesion to the upper nasal mucosa. NLC-based in situ gel showed a 2-fold increase in nasal permeation of the drug over plain RV solution. In situ gelling NLCs showed a 3-fold increase in enzyme inhibition efficacy.

Liposomal nanocarriers for tumor imaging.

PubMed

Erdogan, Suna

2009-04-01

Currently used imaging modalities such as scintigraphy, computed tomography, magnetic resonance imaging and ultrasonography require the sufficient intensity of a corresponding signal from an area of interest to differentiate this area from the surrounding tissues. Targeting of various reporter moieties directly to the specific organs, tissues or tumors provide the highest dose of drug directly where it is needed. Many different types of nanoparticles are currently being studied for applications in nanomedicine. Among particulate drug carriers, liposomes are one of the most extensively studied and possess the most suitable characteristics for encapsulation of many drugs, genes, and diagnostic (imaging) agents. Among the many potential targets for such nanocarriers, tumors have been most often investigated. This review attempts to summarize the currently available information regarding liposomal nanocarriers for cancer imaging.

JPL Electronic Nose: From Sniffing Brain Cancer to Trouble in Space

NASA Technical Reports Server (NTRS)

Homer, Margie L.

2011-01-01

What Is An Electronic Nose? An array of non-specific chemical sensors, controlled and analyzed electronically, which mimics the action of the mammalian nose by recognizing patterns of response. An Enose: (1.) ENose measures background resistance in each sensor and establishes a baseline. (2.) Contaminant comes in contact with sensors on the sensing head. (3.) The sensing films, change physical properties, such as thickness or color, as air composition changes. (4.) Sensor response is recorded by a computer, the change in resistance is computed, and the distributed response pattern of the sensor array is used to identify gases and mixtures of gases. (5. Responses of the sensor array are analyzed and quantified using software developed for the task.

Lipid nanocarriers: influence of lipids on product development and pharmacokinetics.

PubMed

Pathak, Kamla; Keshri, Lav; Shah, Mayank

2011-01-01

Lipid nanocarriers are on the forefront of the rapidly developing field of nanotechnology with several potential applications in drug delivery. Owing to their size-dependent properties, lipid nanoparticles offer the possibility for development of new therapeutics and an alternative system to other colloidal counterparts for drug administration. An important point to be considered in the selection of a lipid for the carrier system is its effect on the properties of the nanocarrier and also its intended use, as different types of lipids differ in their nature. Researchers around the globe have tapped the potential of solid lipid nanoparticles (SLNs) in developing formulation(s) that can be administered by various routes such as oral, ocular, parenteral, topical, and pulmonary. Since the start of this millennium, a new generation of lipid nanoparticles, namely nanostructured lipid carriers (NLCs), lipid drug conjugates (LDCs), and pharmacosomes, has evolved that have the potential to overcome the limitations of SLNs. The current review article presents broad considerations on the influence of various types of lipids on the diverse characteristics of nanocarriers, encompassing their physicochemical, formulation, pharmacokinetic, and cytotoxic aspects.

Nose-to-brain drug delivery: An update on clinical challenges and progress towards approval of anti-Alzheimer drugs.

PubMed

Agrawal, Mukta; Saraf, Swarnlata; Saraf, Shailendra; Antimisiaris, Sophia G; Chougule, Mahavir Bhupal; Shoyele, Sunday A; Alexander, Amit

2018-07-10

According to the Alzheimer Association Report (2017), Alzheimer's disease (AD) is the 6th primary cause of death in the USA, which affects nearly 5.5 million people. In the year 2017 itself, the cost of AD treatment in the USA has been reported to rise to $259 billion. This statistic shows the severity of the disease in the USA which is very much similar across the globe. On the other hand, the treatment remains limited to a few conventional oral medications (approved by FDA). These are mainly acting superficially from mild to the moderate AD. The therapeutic efficacy of the drug is not only affected by its reduced concentration in the brain owing to the existence of blood-brain-barrier (BBB) but also due to its low brain permeability. In this context, the intranasal (IN) route of drug administration has emerged as an alternative route over the systemic (oral and parenteral) drug delivery to the brain. The delivery of the drug via an IN route offers various advantages over systemic drug delivery system, as it directly delivers the drug into the brain via olfactory route. Presence of drug in the olfactory bulb, in turn, increases the drug bioavailability in the brain and reduces the drug degradation as well as wastage of the drug through` systemic clearance. However, there is also some limitation associated with IN like poor drug permeation through the nasal mucosa and mucociliary clearance. The delivery system various through novel strategies (nano drug carrier system, colloidal carriers, mucoadhesive devices, controlled delivery system, pro-drug, etc.) are adapted to overcome the above-stated limitations. Although, after all, such successful research claims, very few of the nose-to-brain drug delivery of anti-AD drugs have gained market approval due to lack of sufficient clinical evidence. Onzetra Xsail® is one such marketed preparations approved for IN delivery used for the treatment of a brain disorder; migraine. In the field of patents also, no work is found

Solid microparticles based on chitosan or methyl-β-cyclodextrin: a first formulative approach to increase the nose-to-brain transport of deferoxamine mesylate

PubMed Central

Rassu, Giovanna; Soddu, Elena; Cossu, Massimo; Brundu, Antonio; Cerri, Guido; Marchetti, Nicola; Ferraro, Luca; Regan, Raymond F.; Giunchedi, Paolo; Gavini, Elisabetta; Dalpiaz, Alessandro

2015-01-01

We propose the formulation and characterization of solid microparticles as nasal drug delivery systems able to increase the nose-to-brain transport of deferoxamine mesylate (DFO), a neuroprotector unable to cross the blood brain barrier and inducing negative peripheral impacts. Spherical chitosan chloride and methyl-β-cyclodextrin microparticles loaded with DFO (DCH and MCD, respectively) were obtained by spray drying. Their volume-surface diameters ranged from 1.77 ± 0.06 μm (DCH) to 3.47 ± 0.05 μm (MCD); the aerodynamic diameters were about 1.1 μm and their drug content was about 30%. In comparison with DCH, MCD enhanced the in vitro DFO permeation across lipophilic membranes, similarly as shown by ex vivo permeation studies across porcine nasal mucosa. Moreover, MCD were able to promote the DFO permeation across monolayers of PC 12 cells (neuron like), but like DCH did not modify the DFO permeation pattern across Caco-2 monolayers (epithelial like). Nasal administration to rats of 200 μg DFO encapsulated in the microparticles resulted in its uptake into the cerebrospinal fluid (CSF) with peak values ranging from 3.83 ± 0.68 μg/mL (DCH) and 14.37 ± 1.69 μg/mL (MCD) 30 min after insufflation of microparticles. No drug CSF uptake was detected after nasal administration of a DFO water solution. The DFO systemic absolute bioavailabilities obtained by DCH and MCD nasal administration were 6% and 15%, respectively. Chitosan chloride and methyl-β-cyclodextrins appear therefore suitable to formulate solid microparticles able to promote the nose to brain uptake of DFO and to limit its systemic exposure. PMID:25620068

Polymer-Based Nanocarriers for Co-Delivery and Combination of Diverse Therapies against Cancers

PubMed Central

Yan, Guowen; Li, Aihua; Zhang, Aitang; Sun, Yong; Liu, Jingquan

2018-01-01

Cancer gives rise to an enormous number of deaths worldwide nowadays. Therefore, it is in urgent need to develop new therapies, among which combined therapies including photothermal therapy (PTT) and chemotherapy (CHT) using polymer-based nanocarriers have attracted enormous interest due to the significantly enhanced efficacy and great progress has been made so far. The preparation of such nanocarriers is a comprehensive task involving the cooperation of nanomaterial science and biomedicine science. In this review, we try to introduce and analyze the structure, preparation and synergistic therapeutic effect of various polymer-based nanocarriers composed of anti-tumor drugs, nano-sized photothermal materials and other possible parts. Our effort may bring benefit to future exploration and potential applications of similar nanocarriers. PMID:29401694

Factorial Design Based Multivariate Modeling and Optimization of Tunable Bioresponsive Arginine Grafted Poly(cystaminebis(acrylamide)-diaminohexane) Polymeric Matrix Based Nanocarriers.

PubMed

Yang, Rongbing; Nam, Kihoon; Kim, Sung Wan; Turkson, James; Zou, Ye; Zuo, Yi Y; Haware, Rahul V; Chougule, Mahavir B

2017-01-03

Desired characteristics of nanocarriers are crucial to explore its therapeutic potential. This investigation aimed to develop tunable bioresponsive newly synthesized unique arginine grafted poly(cystaminebis(acrylamide)-diaminohexane) [ABP] polymeric matrix based nanocarriers by using L9 Taguchi factorial design, desirability function, and multivariate method. The selected formulation and process parameters were ABP concentration, acetone concentration, the volume ratio of acetone to ABP solution, and drug concentration. The measured nanocarrier characteristics were particle size, polydispersity index, zeta potential, and percentage drug loading. Experimental validation of nanocarrier characteristics computed from initially developed predictive model showed nonsignificant differences (p > 0.05). The multivariate modeling based optimized cationic nanocarrier formulation of <100 nm loaded with hydrophilic acetaminophen was readapted for a hydrophobic etoposide loading without significant changes (p > 0.05) except for improved loading percentage. This is the first study focusing on ABP polymeric matrix based nanocarrier development. Nanocarrier particle size was stable in PBS 7.4 for 48 h. The increase of zeta potential at lower pH 6.4, compared to the physiological pH, showed possible endosomal escape capability. The glutathione triggered release at the physiological conditions indicated the competence of cytosolic targeting delivery of the loaded drug from bioresponsive nanocarriers. In conclusion, this unique systematic approach provides rational evaluation and prediction of a tunable bioresponsive ABP based matrix nanocarrier, which was built on selected limited number of smart experimentation.

Chitosan-coated liposome dry-powder formulations loaded with ghrelin for nose-to-brain delivery.

PubMed

Salade, Laurent; Wauthoz, Nathalie; Vermeersch, Marjorie; Amighi, Karim; Goole, Jonathan

2018-06-11

The nose-to-brain delivery of ghrelin loaded in liposomes is a promising approach for the management of cachexia. It could limit the plasmatic degradation of ghrelin and provide direct access to the brain, where ghrelin's specific receptors are located. Anionic liposomes coated with chitosan in either a liquid or a dry-powder formulation were compared. The powder formulation showed stronger adhesion to mucins (89 ± 4% vs 61 ± 4%), higher ghrelin entrapment efficiency (64 ± 2% vs 55 ± 4%), higher enzymatic protection against trypsin (26 ± 2% vs 20 ± 3%) and lower ghrelin storage degradation at 25°C (2.67 ± 1.1% vs 95.64 ± 0.85% after 4 weeks). The powder formulation was also placed in unit-dose system devices that were able to generate an appropriate aerosol characterized by a Dv50 of 38 ± 6 µm, a limited percentage of particles smaller than 10 µm of 4 ± 1% and a reproducible mass delivery (CV: 1.49%). In addition, the device was able to deposit a large amount of powder (52.04% w/w) in the olfactory zone of a 3D-printed nasal cast. The evaluated combination of the powder formulation and the device could provide a promising treatment for cachexia. Copyright © 2018. Published by Elsevier B.V.

Size-Dependent Deposition, Translocation, and Microglial Activation of Inhaled Silver Nanoparticles in the Rodent Nose and Brain

PubMed Central

Patchin, Esther Shin; Anderson, Donald S.; Silva, Rona M.; Uyeminami, Dale L.; Scott, Grace M.; Guo, Ting; Van Winkle, Laura S.; Pinkerton, Kent E.

2016-01-01

Background: Silver nanoparticles (AgNP) are present in personal, commercial, and industrial products, which are often aerosolized. Current understanding of the deposition, translocation, and health-related impacts of AgNP inhalation is limited. Objectives: We determined a) the deposition and retention of inhaled Ag in the nasal cavity from nose-only exposure; b) the timing for Ag translocation to and retention/clearance in the olfactory bulb (OB); and c) whether the presence of Ag in the OB affects microglial activity. Methods: Male Sprague-Dawley rats were exposed nose-only to citrate-buffered 20- or 110-nm AgNP (C20 or C110, respectively) or citrate buffer alone for 6 hr. The nasal cavity and OB were examined for the presence of Ag and for biological responses up to 56 days post-exposure (8 weeks). Results: The highest nasal Ag deposition was observed on Day 0 for both AgNP sizes. Inhalation of aerosolized C20 resulted in rapid translocation of Ag to the OB and in microglial activation at Days 0, 1, and 7. In contrast, inhalation of C110 resulted in a gradual but progressive transport of Ag to and retention in the OB, with a trend for microglial activation to variably be above control. Conclusions: The results of this study show that after rats experienced a 6-hr inhalation exposure to 20- and 110-nm AgNP at a single point in time, Ag deposition in the nose, the rate of translocation to the brain, and subsequent microglial activation in the OB differed depending on AgNP size and time since exposure. Citation: Patchin ES, Anderson DS, Silva RM, Uyeminami DL, Scott GM, Guo T, Van Winkle LS, Pinkerton KE. 2016. Size-dependent deposition, translocation, and microglial activation of inhaled silver nanoparticles in the rodent nose and brain. Environ Health Perspect 124:1870–1875; http://dx.doi.org/10.1289/EHP234 PMID:27152509

Gene delivery nanocarriers of bioactive glass with unique potential to load BMP2 plasmid DNA and to internalize into mesenchymal stem cells for osteogenesis and bone regeneration

NASA Astrophysics Data System (ADS)

Kim, Tae-Hyun; Singh, Rajendra K.; Kang, Min Sil; Kim, Joong-Hyun; Kim, Hae-Won

2016-04-01

The recent development of bioactive glasses with nanoscale morphologies has spurred their specific applications in bone regeneration, for example as drug and gene delivery carriers. Bone engineering with stem cells genetically modified with this unique class of nanocarriers thus holds great promise in this avenue. Here we report the potential of the bioactive glass nanoparticle (BGN) system for the gene delivery of mesenchymal stem cells (MSCs) targeting bone. The composition of 15% Ca-added silica, proven to be bone-bioactive, was formulated into surface aminated mesoporous nanospheres with enlarged pore sizes, to effectively load and deliver bone morphogenetic protein-2 (BMP2) plasmid DNA. The enlarged mesopores were highly effective in loading BMP2-pDNA with an efficiency as high as 3.5 wt% (pDNA w.r.t. BGN), a level more than twice than for small-sized mesopores. The BGN nanocarriers released the genetic molecules in a highly sustained manner (for as long as 2 weeks). The BMP2-pDNA/BGN complexes were effectively internalized to rat MSCs with a cell uptake level of ~73%, and the majority of cells were transfected to express the BMP2 protein. Subsequent osteogenesis of the transfected MSCs was demonstrated by the expression of bone-related genes, including bone sialoprotein, osteopontin, and osteocalcin. The MSCs transfected with BMP2-pDNA/BGN were locally delivered inside a collagen gel to the target calvarium defects. The results showed significantly improved bone regeneration, as evidenced by the micro-computed tomographic, histomorphometric and immunohistochemical analyses. This study supports the excellent capacity of the BGN system as a pDNA-delivery nanocarrier in MSCs, and the engineered system, BMP2-pDNA/BGN with MSCs, may be considered a new promising candidate to advance the therapeutic potential of stem cells through genetic modification, targeting bone defects and diseases.The recent development of bioactive glasses with nanoscale morphologies has

Evaluation of Doxorubicin-loaded 3-Helix Micelles as Nanocarriers

PubMed Central

Dube, Nikhil; Shu, Jessica Y.; Dong, He; Seo, Jai W.; Ingham, Elizabeth; Kheirolomoom, Azadeh; Chen, Pin-Yuan; Forsayeth, John; Bankiewicz, Krystof; Ferrara, Katherine W.; Xu, Ting

2013-01-01

Designing stable drug nanocarriers, 10-30 nm in size, would have significant impact on their transport in circulation, tumor penetration and therapeutic efficacy. In the present study, biological properties of 3-helix micelles loaded with 8 wt% doxorubicin (DOX), ~15 nm in size, were characterized to validate their potential as a nanocarrier platform. DOX-loaded micelles exhibited high stability in terms of size and drug retention in concentrated protein environments similar to conditions after intravenous injections. DOX-loaded micelles were cytotoxic to PPC-1 and 4T1 cancer cells at levels comparable to free DOX. 3-helix micelles can be disassembled by proteolytic degradation of peptide shell to enable drug release and clearance to minimize long-term accumulation. Local administration to normal rat striatum by convection enhanced delivery (CED) showed greater extent of drug distribution and reduced toxicity relative to free drug. Intravenous administration of DOX-loaded 3-helix micelles demonstrated improved tumor half-life and reduced toxicity to healthy tissues in comparison to free DOX. In vivo delivery of DOX-loaded 3-helix micelles through two different routes clearly indicates the potential of 3-helix micelles as safe and effective nanocarriers for cancer therapeutics. PMID:24050265

SAXS Study of Sterically Stabilized Lipid Nanocarriers Functionalized by DNA

NASA Astrophysics Data System (ADS)

Angelov, Borislav; Angelova, Angelina; Filippov, Sergey; Karlsson, Göran; Terrill, Nick; Lesieur, Sylviane; Štěpánek, Petr

2012-03-01

The structure of novel spontaneously self-assembled plasmid DNA/lipid complexes is investigated by means of synchrotron radiation small-angle X-ray scattering (SAXS) and Cryo-TEM imaging. Liquid crystalline (LC) hydrated lipid systems are prepared using the non-ionic lipids monoolein and DOPE-PEG2000 and the cationic amphiphile CTAB. The employed plasmid DNA (pDNA) is encoding for the human protein brain-derived neurotrophic factor (BDNF). A coexistence of nanoparticulate objects with different LC inner organizations is established. A transition from bicontinuous membrane sponges, cubosome intermediates and unilamelar liposomes to multilamellar vesicles, functionalized by pDNA, is favoured upon binding and compaction of pBDNF onto the cationic PEGylated lipid nanocarriers. The obtained sterically stabilized multicompartment nanoobjects, with confined supercoiled plasmid DNA (pBDNF), are important in the context of multicompartment lipid nanocarriers of interest for gene therapy of neurodegenerative diseases.

Novel alginate-based nanocarriers as a strategy to include high concentrations of hydrophobic compounds in hydrogels for topical application.

PubMed

Nguyen, H T P; Munnier, E; Souce, M; Perse, X; David, S; Bonnier, F; Vial, F; Yvergnaux, F; Perrier, T; Cohen-Jonathan, S; Chourpa, I

2015-01-26

The cutaneous penetration of hydrophobic active molecules is of foremost concern in the dermatology and cosmetic formulation fields. The poor solubility in water of those molecules limits their use in hydrophilic forms such as gels, which are favored by patients with chronic skin disease. The aim of this work is to design a novel nanocarrier of hydrophobic active molecules and to determine its potential as an ingredient of a topical form. The nanocarrier consists of an oily core surrounded by a protective shell of alginate, a natural polysaccharide isolated from brown algae. These calcium alginate-based nanocarriers (CaANCs) were prepared at room temperature and without the use of organic solvent by an accelerated nanoemulsification-polymer crosslinking method. The size (hydrodynamic diameter ~200 nm) and surface charge (zeta potential ~ - 30 mV) of the CaANCs are both compatible with their application on skin. CaANCs loaded with a fluorescent label were stable in model hydrophilic galenic forms under different storage conditions. Curcumin was encapsulated in CaANCs with an efficiency of ~95%, fully retaining its antioxidant activity. The application of the curcumin-loaded CaANCs on excised human skin led to a significant accumulation of the active molecules in the upper layers of the skin, asserting the potential of these nanocarriers in active pharmaceutical and cosmetic ingredients topical delivery.

Novel alginate-based nanocarriers as a strategy to include high concentrations of hydrophobic compounds in hydrogels for topical application

NASA Astrophysics Data System (ADS)

Nguyen, H. T. P.; Munnier, E.; Souce, M.; Perse, X.; David, S.; Bonnier, F.; Vial, F.; Yvergnaux, F.; Perrier, T.; Cohen-Jonathan, S.; Chourpa, I.

2015-06-01

The cutaneous penetration of hydrophobic active molecules is of foremost concern in the dermatology and cosmetic formulation fields. The poor solubility in water of those molecules limits their use in hydrophilic forms such as gels, which are favored by patients with chronic skin disease. The aim of this work is to design a novel nanocarrier of hydrophobic active molecules and to determine its potential as an ingredient of a topical form. The nanocarrier consists of an oily core surrounded by a protective shell of alginate, a natural polysaccharide isolated from brown algae. These calcium alginate-based nanocarriers (CaANCs) were prepared at room temperature and without the use of organic solvent by an accelerated nanoemulsification-polymer crosslinking method. The size (hydrodynamic diameter ˜200 nm) and surface charge (zeta potential ˜ - 30 mV) of the CaANCs are both compatible with their application on skin. CaANCs loaded with a fluorescent label were stable in model hydrophilic galenic forms under different storage conditions. Curcumin was encapsulated in CaANCs with an efficiency of ˜95%, fully retaining its antioxidant activity. The application of the curcumin-loaded CaANCs on excised human skin led to a significant accumulation of the active molecules in the upper layers of the skin, asserting the potential of these nanocarriers in active pharmaceutical and cosmetic ingredients topical delivery.

Advanced nanocarriers based on heparin and its derivatives for cancer management.

PubMed

Yang, Xiaoye; Du, Hongliang; Liu, Jiyong; Zhai, Guangxi

2015-02-09

To obtain a satisfying anticancer effect, rationally designed nanocarriers are intensively studied. In this field, heparin and its derivatives have been widely attempted recently as potential component of nanocarriers due to their unique biological and physiochemical features, especially the anticancer activity. This review focuses on state-of-the-art nanocarriers with heparin/heparin derivatives as backbone or coating material. At the beginning, the unique advantages of heparin used in cancer nanotechnology are discussed. After that, different strategies of heparin chemical modification are reviewed, laying the foundation of developing various nanocarriers. Then a systematic summary of diverse nanoparticles with heparin as component is exhibited, involving heparin-drug conjugate, polymeric nanoparticles, nanogels, polyelectrolyte complex nanoparticles, and heparin-coated organic and inorganic nanoparticles. The application of these nanoparticles in various novel cancer therapy (containing targeted therapy, magnetic therapy, photodynamic therapy, and gene therapy) will be highlighted. Finally, future challenges and opportunities of heparin-based biomaterials in cancer nanotechnology are discussed.

Injectable nanocarriers for biodetoxification

NASA Astrophysics Data System (ADS)

Leroux, Jean-Christophe

2007-11-01

Hospitals routinely treat patients suffering from overdoses of drugs or other toxic chemicals as a result of illicit drug consumption, suicide attempts or accidental exposures. However, for many life-threatening situations, specific antidotes are not available and treatment is largely based on emptying the stomach, administering activated charcoal or other general measures of intoxication support. A promising strategy for managing such overdoses is to inject nanocarriers that can extract toxic agents from intoxicated tissues. To be effective, the nanocarriers must remain in the blood long enough to sequester the toxic components and/or their metabolites, and the toxin bound complex must also remain stable until it is removed from the bloodstream. Here, we discuss the principles that govern the use of injectable nanocarriers in biodetoxification and review the pharmacological performance of a number of different approaches.

A Review on Potential of Proteins as an Excipient for Developing a Nano-Carrier Delivery System.

PubMed

Chakraborty, Amrita; Dhar, Pubali

2017-01-01

In neo-age research, nano-materials have emerged as potential tools for the revolution of diagnostic and therapeutic field because of their nano-scale effects, increased surface area-volume ratio, and other beneficial properties. For the last few decades, protein has been regarded as the most attractive and versatile natural bio-macromolecule among all of the available biopolymers. Protein is largely exploited as a nano-carrier system in the pharmaceutical industry due to its low cytotoxocity, biocompatibility, biodegradability, abundant renewable sources, significant attaching ability, clinically useful targeting, and site-specific efficient uptake. This review mainly emphasizes on the latest development and progress achieved in the utilization of protein as a nano-vehicle for a large number of therapeutics such as drugs, genes, hormones, enzymse, nutraceuticals, antibodies, peptides, etc. We also discuss the sources of protein materials, fabrication aspects, advantages, constraints, in vivo and in vitro studies and provide a comparative analysis between the different types of proteins as nano-carriers. The variation of the release pattern and molecular mechanism of the encapsulated molecule with respect to different protein types and various nano-structures are also highlighted here to explore the enormous promises of this novel approach.

A potential non-invasive glioblastoma treatment: Nose-to-brain delivery of farnesylthiosalicylic acid incorporated hybrid nanoparticles.

PubMed

Sekerdag, Emine; Lüle, Sevda; Bozdağ Pehlivan, Sibel; Öztürk, Naile; Kara, Aslı; Kaffashi, Abbas; Vural, Imran; Işıkay, Ilkay; Yavuz, Burҫin; Oguz, Kader Karlı; Söylemezoğlu, Figen; Gürsoy-Özdemir, Yasemin; Mut, Melike

2017-09-10

New drug delivery systems are highly needed in research and clinical area to effectively treat gliomas by reaching a high antineoplastic drug concentration at the target site without damaging healthy tissues. Intranasal (IN) administration, an alternative route for non-invasive drug delivery to the brain, bypasses the blood-brain-barrier (BBB) and eliminates systemic side effects. This study evaluated the antitumor efficacy of farnesylthiosalicylic acid (FTA) loaded (lipid-cationic) lipid-PEG-PLGA hybrid nanoparticles (HNPs) after IN application in rats. FTA loaded HNPs were prepared, characterized and evaluated for cytotoxicity. Rat glioma 2 (RG2) cells were implanted unilaterally into the right striatum of female Wistar rats. 10days later, glioma bearing rats received either no treatment, or 5 repeated doses of 500μM freshly prepared FTA loaded HNPs via IN or intravenous (IV) application. Pre-treatment and post-treatment tumor sizes were determined with MRI. After a treatment period of 5days, IN applied FTA loaded HNPs achieved a significant decrease of 55.7% in tumor area, equal to IV applied FTA loaded HNPs. Herewith, we showed the potential utility of IN application of FTA loaded HNPs as a non-invasive approach in glioblastoma treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Bioelectronic nose and its application to smell visualization.

PubMed

Ko, Hwi Jin; Park, Tai Hyun

2016-01-01

There have been many trials to visualize smell using various techniques in order to objectively express the smell because information obtained from the sense of smell in human is very subjective. So far, well-trained experts such as a perfumer, complex and large-scale equipment such as GC-MS, and an electronic nose have played major roles in objectively detecting and recognizing odors. Recently, an optoelectronic nose was developed to achieve this purpose, but some limitations regarding the sensitivity and the number of smells that can be visualized still persist. Since the elucidation of the olfactory mechanism, numerous researches have been accomplished for the development of a sensing device by mimicking human olfactory system. Engineered olfactory cells were constructed to mimic the human olfactory system, and the use of engineered olfactory cells for smell visualization has been attempted with the use of various methods such as calcium imaging, CRE reporter assay, BRET, and membrane potential assay; however, it is not easy to consistently control the condition of cells and it is impossible to detect low odorant concentration. Recently, the bioelectronic nose was developed, and much improved along with the improvement of nano-biotechnology. The bioelectronic nose consists of the following two parts: primary transducer and secondary transducer. Biological materials as a primary transducer improved the selectivity of the sensor, and nanomaterials as a secondary transducer increased the sensitivity. Especially, the bioelectronic noses using various nanomaterials combined with human olfactory receptors or nanovesicles derived from engineered olfactory cells have a potential which can detect almost all of the smells recognized by human because an engineered olfactory cell might be able to express any human olfactory receptor as well as can mimic human olfactory system. Therefore, bioelectronic nose will be a potent tool for smell visualization, but only if two

Tailored dendritic core-multishell nanocarriers for efficient dermal drug delivery: A systematic top-down approach from synthesis to preclinical testing.

PubMed

Hönzke, Stefan; Gerecke, Christian; Elpelt, Anja; Zhang, Nan; Unbehauen, Michael; Kral, Vivian; Fleige, Emanuel; Paulus, Florian; Haag, Rainer; Schäfer-Korting, Monika; Kleuser, Burkhard; Hedtrich, Sarah

2016-11-28

Drug loaded dendritic core-multishell (CMS) nanocarriers are of especial interest for the treatment of skin diseases, owing to their striking dermal delivery efficiencies following topical applications. CMS nanocarriers are composed of a polyglycerol core, connected by amide-bonds to an inner alkyl shell and an outer methoxy poly(ethylene glycol) shell. Since topically applied nanocarriers are subjected to biodegradation, the application of conventional amide-based CMS nanocarriers (10-A-18-350) has been limited by the potential production of toxic polyglycerol amines. To circumvent this issue, three tailored ester-based CMS nanocarriers (10-E-12-350, 10-E-15-350, 10-E-18-350) of varying inner alkyl chain length were synthesized and comprehensively characterized in terms of particle size, drug loading, biodegradation and dermal drug delivery efficiency. Dexamethasone (DXM), a potent drug widely used for the treatment of inflammatory skin diseases, was chosen as a therapeutically relevant test compound for the present study. Ester- and amide-based CMS nanocarriers delivered DXM more efficiently into human skin than a commercially available DXM cream. Subsequent in vitro and in vivo toxicity studies identified CMS (10-E-15-350) as the most biocompatible carrier system. The anti-inflammatory potency of DXM-loaded CMS (10-E-15-350) nanocarriers was assessed in TNFα supplemented skin models, where a significant reduction of the pro-inflammatory cytokine IL-8 was seen, with markedly greater efficacy than commercial DXM cream. In summary, we report the rational design and characterization of tailored, biodegradable, ester-based CMS nanocarriers, and their subsequent stepwise screening for biocompatibility, dermal delivery efficiency and therapeutic efficacy in a top-down approach yielding the best carrier system for topical applications. Copyright © 2016 Elsevier B.V. All rights reserved.

Brain-Derived Neurotrophic Factor Loaded PS80 PBCA Nanocarrier for In Vitro Neural Differentiation of Mouse Induced Pluripotent Stem Cells

PubMed Central

Chung, Chiu-Yen; Lin, Martin Hsiu-Chu; Lee, I-Neng; Lee, Tsong-Hai; Lee, Ming-Hsueh; Yang, Jen-Tsung

2017-01-01

Brain derived neurotrophic factor (BDNF) can induce neural differentiation in stem cells and has the potential for repair of the nervous system. In this study, a polysorbate 80-coated polybutylcyanoacrylate nanocarrier (PS80 PBCA NC) was constructed to deliver plasmid DNAs (pDNAs) containing BDNF gene attached to a hypoxia-responsive element (HRE-cmvBDNF). The hypoxia-sensing mechanism of BDNF expression and inductiveness of the nano-formulation on mouse induced pluripotent stem cells (iPSCs) to differentiate into neurons following hypoxia was tested in vitro with immunofluorescent staining and Western blotting. The HRE-cmvBDNF appeared to adsorb onto the surface of PS80 PBCA NC, with a resultant mean diameter of 92.6 ± 1.0 nm and zeta potential of −14.1 ± 1.1 mV. HIF-1α level in iPSCs was significantly higher in hypoxia, which resulted in a 51% greater BDNF expression when transfected with PS80 PBCA NC/HRE-cmvBDNF than those without hypoxia. TrkB and phospho-Akt were also elevated which correlated with neural differentiation. The findings suggest that PS80 PBCA NC too can be endocytosed to serve as an efficient vector for genes coupled to the HRE in hypoxia-sensitive cells, and activation of the PI3/Akt pathway in iPSCs by BDNF is capable of neural lineage specification. PMID:28335495

The Research and Applications of Quantum Dots as Nano-Carriers for Targeted Drug Delivery and Cancer Therapy

NASA Astrophysics Data System (ADS)

Zhao, Mei-Xia; Zhu, Bing-Jie

2016-04-01

Quantum dots (QDs), nano-carriers for drugs, can help realize the targeting of drugs, and improve the bioavailability of drugs in biological fields. And, a QD nano-carrier system for drugs has the potential to realize early detection, monitoring, and localized treatments of specific disease sites. In addition, QD nano-carrier systems for drugs can improve stability of drugs, lengthen circulation time in vivo, enhance targeted absorption, and improve the distribution and metabolism process of drugs in organization. So, the development of QD nano-carriers for drugs has become a hotspot in the fields of nano-drug research in recent years. In this paper, we review the advantages and applications of the QD nano-carriers for drugs in biological fields.

A novel nano-carrier transdermal gel against inflammation.

PubMed

Chaudhary, Hema; Kohli, Kanchan; Kumar, Vikash

2014-04-25

The objective was to develop a stable, reproducible and patient non-infringing novel transdermal drug delivery system "nano-carrier transdermal gel" (NCTG) in combination of partial dose replacement of diclofenac diethylamine (DDEA) by curcumin (CRM). The drug content of gel was 99.30 and 97.57% for DDEA and CRM. Plasma samples were analyzed by liquid chromatography with triple-quadrupole tandem mass spectrometer (LC-MS/MS). Data were integrated with Analyst™ and analyzed by WinNonlin; stability parameters were analyzed using Tukey-Kramer multiple comparison test. Its average skin irritation scored 0.49 concluded to be non-irritant, safe for human use and in vivo studies revealed significantly greater extent of absorption and highly significant inhibition (%) of carrageenan induced paw edema. The results also demonstrated that encapsulation of drugs in nano-carrier increases its biological activity due to superior skin penetration potential. Hence, a novel once day transdermal gel of nano-carrier (nano-transfersomes; deformable vesicular) is achieved, to increase systemic availability, subsequent reduction in dose and toxicity of DDEA was developed for the treatment of inflammation. Copyright © 2014 Elsevier B.V. All rights reserved.

Scalable and cleavable polysaccharide nanocarriers for the delivery of chemotherapy drugs.

PubMed

Wang, Hao; Dai, Tingting; Li, Shengli; Zhou, Shuyan; Yuan, Xiaojing; You, Jiayi; Wang, Chenglong; Mukwaya, Vincent; Zhou, Guangdong; Liu, Guojun; Wei, Xiaohui; Dou, Hongjing

2018-05-01

free radical polymerization to facilitate the graft copolymerization-induced self-assembly (GISA) of acrylate monomers with various hydrophobicities to construct cleavable polysaccharide-polyacrylate nanocarriers at a high efficiency with excellent potential for industrial-scale production. We envision that these nanocarriers will contribute to the development of tumor nanotheranostics that combine the biological functionalities of polysaccharides with the unmatched application-specific flexibility of nanocarriers. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Ultrasound-Mediated Local Drug and Gene Delivery Using Nanocarriers

PubMed Central

Zhou, Qiu-Lan; Chen, Zhi-Yi; Yang, Feng

2014-01-01

With the development of nanotechnology, nanocarriers have been increasingly used for curative drug/gene delivery. Various nanocarriers are being introduced and assessed, such as polymer nanoparticles, liposomes, and micelles. As a novel theranostic system, nanocarriers hold great promise for ultrasound molecular imaging, targeted drug/gene delivery, and therapy. Nanocarriers, with the properties of smaller particle size, and long circulation time, would be advantageous in diagnostic and therapeutic applications. Nanocarriers can pass through blood capillary walls and cell membrane walls to deliver drugs. The mechanisms of interaction between ultrasound and nanocarriers are not clearly understood, which may be related to cavitation, mechanical effects, thermal effects, and so forth. These effects may induce transient membrane permeabilization (sonoporation) on a single cell level, cell death, and disruption of tissue structure, ensuring noninvasive, targeted, and efficient drug/gene delivery and therapy. The system has been used in various tissues and organs (in vitro or in vivo), including tumor tissues, kidney, cardiac, skeletal muscle, and vascular smooth muscle. In this review, we explore the research progress and application of ultrasound-mediated local drug/gene delivery with nanocarriers. PMID:25202710

Dual-Targeting Lactoferrin-Conjugated Polymerized Magnetic Polydiacetylene-Assembled Nanocarriers with Self-Responsive Fluorescence/Magnetic Resonance Imaging for In Vivo Brain Tumor Therapy.

PubMed

Fang, Jen-Hung; Chiu, Tsung-Lang; Huang, Wei-Chen; Lai, Yen-Ho; Hu, Shang-Hsiu; Chen, You-Yin; Chen, San-Yuan

2016-03-01

Maintaining a high concentration of therapeutic agents in the brain is difficult due to the restrictions of the blood-brain barrier (BBB) and rapid removal from blood circulation. To enable controlled drug release and enhance the blood-brain barrier (BBB)-crossing efficiency for brain tumor therapy, a new dual-targeting magnetic polydiacetylene nanocarriers (PDNCs) delivery system modified with lactoferrin (Lf) is developed. The PDNCs are synthesized using the ultraviolet (UV) cross-linkable 10,12-pentacosadiynoic acid (PCDA) monomers through spontaneous assembling onto the surface of superparamagnetic iron oxide (SPIO) nanoparticles to form micelles-polymerized structures. The results demonstrate that PDNCs will reduce the drug leakage and further control the drug release, and display self-responsive fluorescence upon intracellular uptake for cell trafficking and imaging-guided tumor treatment. The magnetic Lf-modified PDNCs with magnetic resonance imaging (MRI) and dual-targeting ability can enhance the transportation of the PDNCs across the BBB for tracking and targeting gliomas. An enhanced therapeutic efficiency can be obtained using Lf-Cur (Curcumin)-PDNCs by improving the retention time of the encapsulated Cur and producing fourfold higher Cur amounts in the brain compared to free Cur. Animal studies also confirm that Lf targeting and controlled release act synergistically to significantly suppress tumors in orthotopic brain-bearing rats. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Superparamagnetic Iron Oxide-Loaded Lipid Nanocarriers Incorporated in Thermosensitive In Situ Gel for Magnetic Brain Targeting of Clonazepam.

PubMed

Abbas, Haidy; Refai, Hanan; El Sayed, Nesrine

2018-04-14

The objective of the study was to target clonazepam to the brain through the intranasal olfactory mucosa using nanolipid carriers loaded with superparamagnetic iron oxide nanoparticles (SPIONs) to allow nanocarrier guidance and retention with an external magnetic field. For improved delivery, the nanolipid carriers were incorporated in a thermosensitive mucoadhesive in situ gel. Different nanolipid carriers including solid lipid nanoparticles and nanostructured lipid carriers (NLC) were prepared and characterized with respect to particle size, zeta potential, entrapment efficiency, and in vitro release. The NLC composed of 3 solid lipids (Compritol ® 888, stearic acid, and glyceryl monostearate) and 2 liquid oils (oleic acid and glyceryl monooleate) showed the most satisfactory characteristics and was loaded with SPION (NLC/SPION). Both formulae (NLC and NLC/SPION) were incorporated in an optimized thermosensitive mucoadhesive in situ system composed of 15% pluronic 127 and 0.75% sodium alginate and evaluated for the anticonvulsant action in chemically induced convulsive Swiss Albino mice. The treatment of animals with NLC/SPION significantly prolonged the onset times for convulsion and considerably protected the animals from death. One can thus hope for the emergence of a new intranasal treatment of epilepsy with consequent decrease in peripheral side effects of clonazepam. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Emerging role of nanocarriers to increase the solubility and bioavailability of curcumin.

PubMed

Mohanty, Chandana; Das, Manasi; Sahoo, Sanjeeb K

2012-11-01

Curcumin is a safe, affordable and natural bioactive molecule of turmeric (Curcuma longa). It has gained considerable attention in recent years for its multiple pharmacological activities. However, its optimum pharmaceutical potential has been limited by its lack of aqueous solubility and poor bioavailability. To mitigate the above limitations, recently various nanostructured water-soluble delivery systems were developed to increase the solubility and bioavailability of curcumin. Major reasons contributing to the low bioavailability of curcumin appear to be owing to its poor solubility, low absorption, rapid metabolism and rapid systemic elimination. The present review summarizes the strategies using curcumin in various nanocarrier delivery systems to overcome poor solubility and inconsistent bioavailability of curcumin and describes the current status and challenges for the future. The development of various drug delivery systems to deliver curcumin will certainly provide a step up towards augmenting the therapeutic activity of curcumin thereby increasing the solubility and bioavailability of curcumin. However, the future of such delivery technology will be highly dependent on the development of safe, non-toxic and non-immunogenic nanocarriers.

The sense of touch in the star-nosed mole: from mechanoreceptors to the brain

PubMed Central

Catania, Kenneth C.

2011-01-01

Star-nosed moles are somatosensory specialists that explore their environment with 22 appendages that ring their nostrils. The appendages are covered with sensory domes called Eimer's organs. Each organ is associated with a Merkel cell–neurite complex, a lamellated corpuscle, and a series of 5–10 free nerve endings that form a circle of terminal swellings. Anatomy and electrophysiological recordings suggest that Eimer's organs detect small shapes and textures. There are parallels between the organization of the mole's somatosensory system and visual systems of other mammals. The centre of the star is a tactile fovea used for detailed exploration of objects and prey items. The tactile fovea is over-represented in the neocortex, and this is evident in the modular, anatomically visible representation of the star. Multiple maps of the star are visible in flattened cortical preparations processed for cytochrome oxidase or NADPH-diaphorase. Star-nosed moles are the fastest known foragers among mammals, able to identify and consume a small prey item in 120 ms. Together these behavioural and nervous system specializations have made star-nosed moles an intriguing model system for examining general and specialized aspects of mammalian touch. PMID:21969683

Preparation of silica nanoparticles loaded with nootropics and their in vivo permeation through blood-brain barrier.

PubMed

Jampilek, Josef; Zaruba, Kamil; Oravec, Michal; Kunes, Martin; Babula, Petr; Ulbrich, Pavel; Brezaniova, Ingrid; Opatrilova, Radka; Triska, Jan; Suchy, Pavel

2015-01-01

The blood-brain barrier prevents the passage of many drugs that target the central nervous system. This paper presents the preparation and characterization of silica-based nanocarriers loaded with piracetam, pentoxifylline, and pyridoxine (drugs from the class of nootropics), which are designed to enhance the permeation of the drugs from the circulatory system through the blood-brain barrier. Their permeation was compared with non-nanoparticle drug substances (bulk materials) by means of an in vivo model of rat brain perfusion. The size and morphology of the nanoparticles were characterized by transmission electron microscopy. The content of the drug substances in silica-based nanocarriers was analysed by elemental analysis and UV spectrometry. Microscopic analysis of visualized silica nanocarriers in the perfused brain tissue was performed. The concentration of the drug substances in the tissue was determined by means of UHPLC-DAD/HRMS LTQ Orbitrap XL. It was found that the drug substances in silica-based nanocarriers permeated through the blood brain barrier to the brain tissue, whereas bulk materials were not detected in the brain.

Preparation of Silica Nanoparticles Loaded with Nootropics and Their In Vivo Permeation through Blood-Brain Barrier

PubMed Central

Zaruba, Kamil; Kunes, Martin; Ulbrich, Pavel; Brezaniova, Ingrid; Triska, Jan; Suchy, Pavel

2015-01-01

The blood-brain barrier prevents the passage of many drugs that target the central nervous system. This paper presents the preparation and characterization of silica-based nanocarriers loaded with piracetam, pentoxifylline, and pyridoxine (drugs from the class of nootropics), which are designed to enhance the permeation of the drugs from the circulatory system through the blood-brain barrier. Their permeation was compared with non-nanoparticle drug substances (bulk materials) by means of an in vivo model of rat brain perfusion. The size and morphology of the nanoparticles were characterized by transmission electron microscopy. The content of the drug substances in silica-based nanocarriers was analysed by elemental analysis and UV spectrometry. Microscopic analysis of visualized silica nanocarriers in the perfused brain tissue was performed. The concentration of the drug substances in the tissue was determined by means of UHPLC-DAD/HRMS LTQ Orbitrap XL. It was found that the drug substances in silica-based nanocarriers permeated through the blood brain barrier to the brain tissue, whereas bulk materials were not detected in the brain. PMID:26075264

Nanocarrier-mediated drugs targeting cancer stem cells: an emerging delivery approach.

PubMed

Malhi, Sarandeep; Gu, Xiaochen

2015-07-01

Cancer stem cells (CSCs) play an important role in the development of drug resistance, metastasis and recurrence. Current conventional therapies do not commonly target CSCs. Nanocarrier-based delivery systems targeting cancer cells have entered a new era of treatment, where specific targeting to CSCs may offer superior outcomes to efficient cancer therapies. This review discusses the involvement of CSCs in tumor progression and relevant mechanisms associated with CSCs resistance to conventional chemo- and radio-therapies. It highlights CSCs-targeted strategies that are either under evaluation or could be explored in the near future, with a focus on various nanocarrier-based delivery systems of drugs and nucleic acids to CSCs. Novel nanocarriers targeting CSCs are presented in a cancer-specific way to provide a current perspective on anti-CSCs therapeutics. The field of CSCs-targeted therapeutics is still emerging with a few small molecules and macromolecules currently proving efficacy in clinical trials. However considering the complexities of CSCs and existing delivery difficulties in conventional anticancer therapies, CSC-specific delivery systems would face tremendous technical and clinical challenges. Nanocarrier-based approaches have demonstrated significant potential in specific drug delivery and targeting; their success in CSCs-targeted drug delivery would not only significantly enhance anticancer treatment but also address current difficulties associated with cancer resistance, metastasis and recurrence.

Food Protein Based Core-Shell Nanocarriers for Oral Drug Delivery: Effect of Shell Composition on in Vitro and in Vivo Functional Performance of Zein Nanocarriers.

PubMed

Alqahtani, Mohammed S; Islam, M Saiful; Podaralla, Satheesh; Kaushik, Radhey S; Reineke, Joshua; Woyengo, Tofuko; Perumal, Omathanu

2017-03-06

The study was aimed at systematically investigating the influence of shell composition on the particle size, stability, release, cell uptake, permeability, and in vivo gastrointestinal distribution of food protein based nanocarriers for oral delivery applications. Three different core-shell nanocarriers were prepared using food-grade biopolymers including zein-casein (ZC) nanoparticles, zein-lactoferrin (ZLF), nanoparticles and zein-PEG (ZPEG) micelles. Nile red was used as a model hydrophobic dye for in vitro studies. The nanocarriers had negative, positive, and neutral charge, respectively. All three nanocarriers had a particle size of less than 200 nm and a low polydispersity index. The nanoparticles were stable at gastrointestinal pH (2-9) and ionic strength (10-200 mM). The nanocarriers sustained the release of Nile red in simulated gastric and intestinal fluids. ZC nanoparticles showed the slowest release followed by ZLF nanoparticles and ZPEG micelles. The nanocarriers were taken up by endocytosis in Caco-2 cells. ZPEG micelles showed the highest cell uptake and transepithelial permeability followed by ZLF and ZC nanoparticles. ZPEG micelles also showed P-gp inhibitory activity. All three nanocarriers showed bioadhesive properties. Cy 5.5, a near IR dye, was used to study the in vivo biodistribution of the nanocarriers. The nanocarriers showed longer retention in the rat gastrointestinal tract compared to the free dye. Among the three formulations, ZC nanoparticles was retained the longest in the rat gastrointestinal tract (≥24 h). Overall, the outcomes from this study demonstrate the structure-function relationship of core-shell protein nanocarriers. The findings from this study can be used to develop food protein based oral drug delivery systems with specific functional attributes.

Design and Application of Multifunctional DNA Nanocarriers for Therapeutic Delivery

PubMed Central

Charoenphol, Phapanin; Bermudez, Harry

2013-01-01

The unique programmability of nucleic acids offers versatility and flexibility in the creation of self-assembled DNA nanostructures. To date, many three-dimensional DNA architectures have been precisely formed of varying sizes and shapes. Their biocompatibility, biodegradability, and high intrinsic stability in physiological environments emphasize their emerging use as carriers for drug and gene delivery. Furthermore, DNA nanocarriers have been shown to enter cells efficiently and without the aid of transfection reagents. A key strength of DNA nanocarriers over other delivery systems is their modularity and their ability to control the spatial distribution of cargoes and ligands. Optimizing DNA nanocarrier properties to dictate their localization, uptake, and intracellular trafficking is also possible. In this review, we present design considerations for DNA nanocarriers and examples of their use in the context of therapeutic delivery applications. The assembly of DNA nanocarriers and approaches for loading and releasing cargo are described. The stability and safety of DNA nanocarriers is also discussed, with particular attention to the in vivo physiological environment. Mechanisms of cellular uptake and intracellular trafficking are examined, and we conclude with strategies to enhance the delivery efficiency of DNA nanocarriers. PMID:23896566

Spikes, Local Field Potentials, and Electrocorticogram Characterization during Motor Learning in Rats for Brain Machine Interface Tasks.

PubMed

Marzullo, T C; Dudley, J R; Miller, C R; Trejo, L; Kipke, D R

2005-01-01

Brain machine interface development typically falls into two arenas, invasive extracellular recording and non-invasive electroencephalogram recording methods. The relationship between action potentials and field potentials is not well understood, and investigation of interrelationships may improve design of neuroprosthetic control systems. Rats were trained on a motor learning task whereby they had to insert their noses into an aperture while simultaneously pressing down on levers with their forepaws; spikes, local field potentials (LFPs), and electrocorticograms (ECoGs) over the motor cortex were recorded and characterized. Preliminary results suggest that the LFP activity in lower cortical layers oscillates with the ECoG.

Intracellular delivery of proteins by nanocarriers.

PubMed

Ray, Moumita; Lee, Yi-Wei; Scaletti, Federica; Yu, Ruijin; Rotello, Vincent M

2017-04-01

Intracellular delivery of proteins is potentially a game-changing approach for therapeutics. However, for most applications, the protein needs to access the cytosol to be effective. A wide variety of strategies have been developed for protein delivery, however access of delivered protein to the cytosol without acute cytotoxicity remains a critical issue. In this review we discuss recent trends in protein delivery using nanocarriers, focusing on the ability of these strategies to deliver protein into the cytosol.

Superiority of liquid crystalline cubic nanocarriers as hormonal transdermal vehicle: comparative human skin permeation-supported evidence.

PubMed

Mohyeldin, Salma M; Mehanna, Mohammed M; Elgindy, Nazik A

2016-08-01

The aim of this investigation was to explore the feasibility of various nanocarriers to enhance progesterone penetration via the human abdominal skin. Four progesterone-loaded nanocarriers; cubosomes, nanoliposomes, nanoemulsions and nanomicelles were formulated and characterized regarding particle size, zeta potential, % drug encapsulation and in vitro release. Structural elucidation of each nanoplatform was performed using transmission electron microscopy. Ex vivo skin permeation, deposition ability and histopathological examination were evaluated using Franz diffusion cells. Each nanocarrier was fabricated with a negative surface, nanometric size (≤ 270 nm), narrow size distribution and reasonable encapsulation efficiency. In vitro progesterone release showed a sustained release pattern for 24 h following a non-Fickian transport diffusion mechanism. All nanocarriers exhibited higher transdermal flux relative to free progesterone. Cubosomes revealed a higher skin penetration with transdermal steady flux of 48.57.10(-2) ± 0.7 µg/cm(2) h. Nanoliposomes offered a higher percentage of skin progesterone deposition compared to other nanocarriers. Based on the histopathological examination, cubosomes and nanoliposomes were found to be biocompatible for transdermal application. Confocal laser scanning microscopy confirmed the ability of fluoro-labeled cubosomes to penetrate through the whole skin layers. The elaborated cubosomes proved to be a promising non-invasive nanocarrier for transdermal hormonal delivery.

Evaluation of neuropeptide loaded trimethyl chitosan nanoparticles for nose to brain delivery.

PubMed

Kumar, Manoj; Pandey, Ravi Shankar; Patra, Kartik Chandra; Jain, Sunil Kumar; Soni, Muarai Lal; Dangi, Jawahar Singh; Madan, Jitender

2013-10-01

Leucine-enkephalin (Leu-Enk) is a neurotransmitter or neuromodulator in pain transmission. Due to non-addictive opioid analgesic activity of this peptide, it might have great potential in pain management. Leu-Enk loaded N-trimethyl chitosan (TMC) nanoparticles were prepared and evaluated as a brain delivery vehicle via nasal route. TMC biopolymer was synthesized and analyzed by (1)H NMR spectroscopy. TMC nanoparticles were prepared by ionic gelation method. Mean peptide encapsulation efficiency and loading capacity were 78.28±3.8% and 14±1.3%, respectively. Mean particle size, polydispersity index and zeta potential were found to be 443±23 nm, 0.317±0.17 and +15±2 mV respectively for optimized formulations. Apparent permeability coefficient (Papp) of Leu-Enk released from nanoparticles across the porcine nasal mucosa was determined to be 7.45±0.30×10(-6) cm s(-1). Permeability of Leu-Enk released from nanoparticles was 35 fold improved from the nasal mucosa as compared to Leu-Enk solution. Fluorescent microscopy of brain sections of mice showed higher accumulation of fluorescent marker NBD-F labelled Leu-Enk, when administered nasally by TMC nanoparticles, while low brain uptake of marker solution was observed. Furthermore, enhancement in brain uptake resulted into significant improvement in the observed antinociceptive effect of Leu-Enk as evidenced by hot plate and acetic acid induced writhing assay. Copyright © 2013 Elsevier B.V. All rights reserved.

Poly(ethylene glycol) (PEG)-lactic acid nanocarrier-based degradable hydrogels for restoring the vaginal microenvironment

PubMed Central

Rajan, Sujata Sundara; Turovskiy, Yevgeniy; Singh, Yashveer; Chikindas, Michael L.; Sinko, Patrick J.

2014-01-01

Women with bacterial vaginosis (BV) display reduced vaginal acidity, which make them susceptible to associated infections such as HIV. In the current study, poly(ethylene glycol) (PEG) nanocarrier-based degradable hydrogels were developed for the controlled release of lactic acid in the vagina of BV-infected women. PEG-lactic acid (PEG-LA) nanocarriers were prepared by covalently attaching lactic acid to 8-arm PEG-SH via cleavable thioester bonds. PEG-LA nanocarriers with 4 copies of lactic acid per molecule provided controlled release of lactic acid with a maximum release of 23% and 47% bound lactic acid in phosphate buffered saline (PBS, pH 7.4) and acetate buffer (AB, pH 4.3), respectively. The PEG nanocarrier-based hydrogels were formed by cross-linking the PEG-LA nanocarriers with 4-arm PEG-NHS via degradable thioester bonds. The nanocarrier-based hydrogels formed within 20 min under ambient conditions and exhibited an elastic modulus that was 100-fold higher than the viscous modulus. The nanocarrier-based degradable hydrogels provided controlled release of lactic acid for several hours; however, a maximum release of only 10%–14% bound lactic acid was observed possibly due to steric hindrance of the polymer chains in the cross-linked hydrogel. In contrast, hydrogels with passively entrapped lactic acid showed burst release with complete release within 30 min. Lactic acid showed antimicrobial activity against the primary BV pathogen Gardnerella vaginalis with a minimum inhibitory concentration (MIC) of 3.6 mg/ml. In addition, the hydrogels with passively entrapped lactic acid showed retained antimicrobial activity with complete inhibition G. vaginalis growth within 48 h. The results of the current study collectively demonstrate the potential of PEG nanocarrier-based hydrogels for vaginal administration of lactic acid for preventing and treating BV. PMID:25223229

Enhanced Delivery and Effects of Acid Sphingomyelinase by ICAM-1-Targeted Nanocarriers in Type B Niemann-Pick Disease Mice.

PubMed

Garnacho, Carmen; Dhami, Rajwinder; Solomon, Melani; Schuchman, Edward H; Muro, Silvia

2017-07-05

Acid sphingomyelinase deficiency in type B Niemann-Pick disease leads to lysosomal sphingomyelin storage, principally affecting lungs, liver, and spleen. Infused recombinant enzyme is beneficial, yet its delivery to the lungs is limited and requires higher dosing than liver and spleen, leading to potentially adverse reactions. Previous studies showed increased enzyme pulmonary uptake by nanocarriers targeted to ICAM-1, a protein overexpressed during inflammation. Here, using polystyrene and poly(lactic-co-glycolic acid) nanocarriers, we optimized lung delivery by varying enzyme dose and nanocarrier concentration, verified endocytosis and lysosomal trafficking in vivo, and evaluated delivered activity and effects. Raising the enzyme load of nanocarriers progressively increased absolute enzyme delivery to all lung, liver, and spleen, over the naked enzyme. Varying nanocarrier concentration inversely impacted lung versus liver and spleen uptake. Mouse intravital and postmortem examination verified endocytosis, transcytosis, and lysosomal trafficking using nanocarriers. Compared to naked enzyme, nanocarriers increased enzyme activity in organs and reduced lung sphingomyelin storage and macrophage infiltration. Although old mice with advanced disease showed reactivity (pulmonary leukocyte infiltration) to injections, including buffer without carriers, antibody, or enzyme, younger mice with mild disease did not. We conclude that anti-ICAM nanocarriers may result in effective lung enzyme therapy using low enzyme doses. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Multiple-Targeted Graphene-based Nanocarrier for Intracellular Imaging of mRNAs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Ying; Li, Zhaohui; Liu, Misha

Simultaneous detection and imaging of multiple intracellular messenger RNA (mRNAs) hold great significant for early cancer diagnostics and preventive medicine development. Herein, we propose a multiple-targeted graphene oxide (GO) nanocarrier that can simultaneously detect and image different type mRNAs in living cells. First of all, in vitro detection of multiple targets have been realized successfully based on the multiple-targeted GO nanocarrier with linear relationship ranging from 3 nM to 200 nM, as well as sensitive detection limit of 1.84 nM for manganese superoxide dismutase (Mn-SOD) mRNA and 2.45 nM for β-actin mRNA. Additionally, this nanosensing platform composed of fluorescent labeledmore » single strand DNA probes and GO nanocarrier can identify Mn-SOD mRNA and endogenous mRNA of β-actin in living cancer cells, showing rapid response, high specificity, nuclease stability, and good biocompatibility during the cell imaging. Thirdly, changes of the expression levels of mRNA in living cells before or after the drug treatment can be monitored successfully. By using multiple ssDNA as probes and GO nanocarrier as the cellular delivery cargo, the proposed simultaneous multiple-targeted sensing platform will be of great potential as a powerful tool for intracellular trafficking process from basic research to clinical diagnosis.« less

Nanotechnology and nanocarrier-based approaches on treatment of degenerative diseases

NASA Astrophysics Data System (ADS)

Chowdhury, Anindita; Kunjiappan, Selvaraj; Panneerselvam, Theivendren; Somasundaram, Balasubramanian; Bhattacharjee, Chiranjib

2017-04-01

Degenerative diseases are results of deterioration of cells and tissues with aging either by unhealthy lifestyle or normal senescence. The degenerative disease likely affects central nervous system and cardiovascular system to a great extent. Certain medications and therapies have emerged for the treatment of degenerative diseases, but in most cases bearing with poor solubility, lower bioavailability, drug resistance, and incapability to cross the blood-brain barrier (BBB). Hence, it has to be overcome with conventional treatment system; in this connection, nanotechnology has gained a great deal of interest in recent years. Moreover, nanotechnology and nanocarrier-based approach drug delivery system could revolutionize the treatment of degenerative diseases by faster absorption of drug, targeted interaction at specific site, and its release in a controlled manner into human body with minimal side effects. The core objective of this review is to customize and formulate therapeutically active molecules with specific site of action and without affecting other organs and tissues to obtain effective result in the improvement of quality of health. In addition, the review provides a concise insight into the recent developments and applications of nanotech and nanocarrier-based drug delivery for the treatment of various degenerative diseases.

Optimization of cell receptor-specific targeting through multivalent surface decoration of polymeric nanocarriers

PubMed Central

D’Addio, Suzanne M.; Baldassano, Steven; Shi, Lei; Cheung, Lila; Adamson, Douglas H.; Bruzek, Matthew; Anthony, John E.; Laskin, Debra L.; Sinko, Patrick J.; Prud’homme, Robert K.

2013-01-01

Treatment of tuberculosis is impaired by poor drug bioavailability, systemic side effects, patient non-compliance, and pathogen resistance to existing therapies. The mannose receptor (MR) is known to be involved in the recognition and internalization of Mycobacterium tuberculosis. We present a new assembly process to produce nanocarriers with variable surface densities of mannose targeting ligands in a single step, using kinetically-controlled, block copolymer-directed assembly. Nanocarrier association with murine macrophage J774 cells expressing the MR is examined as a function of incubation time and temperature, nanocarrier size, dose, and PEG corona properties. Amphiphilic diblock copolymers are prepared with terminal hydroxyl, methoxy, or mannoside functionality and incorporated into nanocarrier formulations at specific ratios by Flash NanoPrecipitation. Association of nanocarriers protected by a hydroxyl-terminated PEG corona with J774 cells is size dependent, while nanocarriers with methoxy-terminated PEG coronas do not associate with cells, regardless of size. Specific targeting of the MR is investigated using nanocarriers having 0-75% mannoside-terminated PEG chains in the PEG corona. This is a wider range of mannose densities than has been previously studied. Maximum nanocarrier association is attained with 9% mannoside-terminated PEG chains, increasing uptake more than 3-fold compared to non-targeted nanocarriers with a 5 kg mol−1 methoxy-terminated PEG corona. While a 5 kg mol−1 methoxy-terminated PEG corona prevents non-specific uptake, a 1.8 kg mol−1 methoxy-terminated PEG corona does not sufficiently protect the nanocarriers from nonspecific association. There is continuous uptake of MR-targeted nanocarriers at 37°C, but a saturation of association at 4°C. The majority of targeted nanocarriers associate with J774E cells are internalized at 37°C and uptake is receptor-dependent, diminishing with competitive inhibition by dextran. This

Numerical Comparison of Nasal Aerosol Administration Systems for Efficient Nose-to-Brain Drug Delivery.

PubMed

Dong, Jingliang; Shang, Yidan; Inthavong, Kiao; Chan, Hak-Kim; Tu, Jiyuan

2017-12-29

Nose-to-brain drug administration along the olfactory and trigeminal nerve pathways offers an alternative route for the treatment of central nervous system (CNS) disorders. The characterization of particle deposition remains difficult to achieve in experiments. Alternative numerical approach is applied to identify suitable aerosol particle size with maximized inhaled doses. This study numerically compared the drug delivery efficiency in a realistic human nasal cavity between two aerosol drug administration systems targeting the olfactory region: the aerosol mask system and the breath-powered bi-directional system. Steady inhalation and exhalation flow rates were applied to both delivery systems. The discrete phase particle tracking method was employed to capture the aerosol drug transport and deposition behaviours in the nasal cavity. Both overall and regional deposition characteristics were analysed in detail. The results demonstrated the breath-powered drug delivery approach can produce superior olfactory deposition with peaking olfactory deposition fractions for diffusive 1 nm particles and inertial 10 μm. While for particles in the range of 10 nm to 2 μm, no significant olfactory deposition can be found, indicating the therapeutic agents should avoid this size range when targeting the olfactory deposition. The breath-powered bi-directional aerosol delivery approach shows better drug delivery performance globally and locally, and improved drug administration doses can be achieved in targeted olfactory region.

Plasmonic nanocarrier grid-enhanced Raman sensor for studies of anticancer drug delivery.

PubMed

Kurzątkowska, Katarzyna; Santiago, Ty; Hepel, Maria

2017-05-15

Targeted drug delivery systems using nanoparticle nanocarriers offer remarkable promise for cancer therapy by discriminating against devastating cytotoxicity of chemotherapeutic drugs to healthy cells. To aid in the development of new drug nanocarriers, we propose a novel plasmonic nanocarrier grid-enhanced Raman sensor which can be applied for studies and testing of drug loading onto the nanocarriers, attachment of targeting ligands, dynamics of drug release, assessment of nanocarrier stability in biological environment, and general capabilities of the nanocarrier. The plasmonic nanogrid sensor offers strong Raman enhancement due to the overlapping plasmonic fields emanating from the nearest-neighbor gold nanoparticle nanocarriers and creating the enhancement "hot spots". The sensor has been tested for immobilization of an anticancer drug gemcitabine (2',2'-difluoro-2'-deoxycytidine, GEM) which is used in treatment of pancreatic tumors. The drawbacks of currently applied treatment include high systemic toxicity, rapid drug decay, and low efficacy (ca. 20%). Therefore, the development of a targeted GEM delivery system is highly desired. We have demonstrated that the proposed nanocarrier SERS sensor can be utilized to investigate attachment of targeting ligands to nanocarriers (attachment of folic acid ligand recognized by folate receptors of cancer cells is described). Further testing of the nanocarrier SERS sensor involved drug release induced by lowering pH and increasing GSH levels, both occurring in cancer cells. The proposed sensor can be utilized for a variety of drugs and targeting ligands, including those which are Raman inactive, since the linkers can act as the Raman markers, as illustrated with mercaptobenzoic acid and para-aminothiophenol. Copyright © 2017 Elsevier B.V. All rights reserved.

Bio-Benchmarking of Electronic Nose Sensors

PubMed Central

Berna, Amalia Z.; Anderson, Alisha R.; Trowell, Stephen C.

2009-01-01

Background Electronic noses, E-Noses, are instruments designed to reproduce the performance of animal noses or antennae but generally they cannot match the discriminating power of the biological original and have, therefore, been of limited utility. The manner in which odorant space is sampled is a critical factor in the performance of all noses but so far it has been described in detail only for the fly antenna. Methodology Here we describe how a set of metal oxide (MOx) E-Nose sensors, which is the most commonly used type, samples odorant space and compare it with what is known about fly odorant receptors (ORs). Principal Findings Compared with a fly's odorant receptors, MOx sensors from an electronic nose are on average more narrowly tuned but much more highly correlated with each other. A set of insect ORs can therefore sample broader regions of odorant space independently and redundantly than an equivalent number of MOx sensors. The comparison also highlights some important questions about the molecular nature of fly ORs. Conclusions The comparative approach generates practical learnings that may be taken up by solid-state physicists or engineers in designing new solid-state electronic nose sensors. It also potentially deepens our understanding of the performance of the biological system. PMID:19641604

Mucin-mediated nanocarrier disassembly for triggered uptake of oligonucleotides as a delivery strategy for the potential treatment of mucosal tumours

NASA Astrophysics Data System (ADS)

Martirosyan, A.; Olesen, M. J.; Fenton, R. A.; Kjems, J.; Howard, K. A.

2016-06-01

This work demonstrates gastric mucin-triggered nanocarrier disassembly for release of antisense oligonucleotides and consequent unassisted cellular entry as a novel oral delivery strategy. A fluorescence activation-based reporter system was used to investigate the interaction and mucin-mediated disassembly of chitosan-based nanocarriers containing a 13-mer DNA oligonucleotide with a flanked locked RNA nucleic acid gapmer design. Gastric mucins were shown to trigger gapmer release from nanocarriers that was dependent on the interaction time, mucin concentration and N : P ratio with a maximal release at N : P 10. In contrast to siRNA, naked gapmers exhibited uptake into mucus producing HT-MTX mono-cultures and HT-MTX co-cultured with the carcinoma epithelial cell line Caco-2. Importantly, in vivo gapmer uptake was observed in epithelial tissue 30 min post-injection in murine intestinal loops. The findings present a mucosal design-based system tailored for local delivery of oligonucleotides that may maximize the effectiveness of gene silencing therapeutics within tumours at mucosal sites.This work demonstrates gastric mucin-triggered nanocarrier disassembly for release of antisense oligonucleotides and consequent unassisted cellular entry as a novel oral delivery strategy. A fluorescence activation-based reporter system was used to investigate the interaction and mucin-mediated disassembly of chitosan-based nanocarriers containing a 13-mer DNA oligonucleotide with a flanked locked RNA nucleic acid gapmer design. Gastric mucins were shown to trigger gapmer release from nanocarriers that was dependent on the interaction time, mucin concentration and N : P ratio with a maximal release at N : P 10. In contrast to siRNA, naked gapmers exhibited uptake into mucus producing HT-MTX mono-cultures and HT-MTX co-cultured with the carcinoma epithelial cell line Caco-2. Importantly, in vivo gapmer uptake was observed in epithelial tissue 30 min post-injection in murine intestinal

Advances in Electronic-Nose Technologies Developed for Biomedical Applications

PubMed Central

Wilson, Alphus D.; Baietto, Manuela

2011-01-01

The research and development of new electronic-nose applications in the biomedical field has accelerated at a phenomenal rate over the past 25 years. Many innovative e-nose technologies have provided solutions and applications to a wide variety of complex biomedical and healthcare problems. The purposes of this review are to present a comprehensive analysis of past and recent biomedical research findings and developments of electronic-nose sensor technologies, and to identify current and future potential e-nose applications that will continue to advance the effectiveness and efficiency of biomedical treatments and healthcare services for many years. An abundance of electronic-nose applications has been developed for a variety of healthcare sectors including diagnostics, immunology, pathology, patient recovery, pharmacology, physical therapy, physiology, preventative medicine, remote healthcare, and wound and graft healing. Specific biomedical e-nose applications range from uses in biochemical testing, blood-compatibility evaluations, disease diagnoses, and drug delivery to monitoring of metabolic levels, organ dysfunctions, and patient conditions through telemedicine. This paper summarizes the major electronic-nose technologies developed for healthcare and biomedical applications since the late 1980s when electronic aroma detection technologies were first recognized to be potentially useful in providing effective solutions to problems in the healthcare industry. PMID:22346620

Nanocarriers in advanced drug targeting: setting novel paradigm in cancer therapeutics.

PubMed

Akhter, Md Habban; Rizwanullah, Md; Ahmad, Javed; Ahsan, Mohamed Jawed; Mujtaba, Md Ali; Amin, Saima

2018-08-01

Cancer has been growing nowadays consequently high number of death ascertained worldwide. The medical intervention involves chemotherapy, radiation therapy and surgical removal. This conventional technique lacking targeting potential and harm the normal cells. In drug treatment regimen, the combination therapy is preferred than single drug treatment module due to higher internalization of chemotherapeutics in the cancer cells both by enhance permeation retention effect and by direct cell apoptosis. The cancer therapeutics involves different methodologies of delivering active moiety to the target site. The active and passive transport mode of chemotherapeutic targeting utilizes advance nanocarriers. The nanotechnological strategic treatment applying advance nanocarrier greatly helps in mitigating the cancer prevalence. The nanocarrier-incorporating nanodrug directed for specific area appealed scientist across the globe and issues to be addressed in this regard. Therefore, various techniques and approaches invented to meet the objectives. With the advances in nanomedicine and drug delivery, this review briefly focused on various modes of nanodrug delivery including nanoparticles, liposomes, dendrimer, quantum dots, carbon nanotubes, metallic nanoparticles, nanolipid carrier (NLC), gold nanoshell, nanosize cantilevers and nanowire that looks promising and generates a novel horizon in cancer therapeutics.

Development of biodegradable hyperbranched core-multishell nanocarriers for efficient topical drug delivery.

PubMed

Du, Fang; Hönzke, Stefan; Neumann, Falko; Keilitz, Juliane; Chen, Wei; Ma, Nan; Hedtrich, Sarah; Haag, Rainer

2016-11-28

The topical application of drugs allows for a local application in skin disease and can reduce side effects. Here we present biodegradable core-multishell (CMS) nanocarriers which are composed of a hyperbranched polyglycerol core functionalized with diblock copolymers consisting of polycaprolactone (PCL) and poly(ethylene glycol) (mPEG) as the outer shell. The anti-inflammatory drug Dexamethasone (Dexa) was loaded into these CMS nanocarriers. DLS results suggested that Dexa loaded nanoparticles mostly act as a unimolecular carrier system. With longer PCL segments, a better transport capacity is observed. In vitro skin permeation studies showed that CMS nanocarriers could improve the Nile red penetration through the skin by up to 7 times, compared to a conventional cream formulation. Interestingly, covalently FITC-labeled CMS nanocarriers remain in the stratum corneum layer. This suggests the enhancement is due to the release of cargo after being transported into the stratum corneum by the CMS nanocarriers. In addition, the hPG-PCL-mPEG CMS nanocarriers exhibited good stability, low cytotoxicity, and their production can easily be scaled up, which makes them promising nanocarriers for topical drug delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

Ceramic nanocarriers: versatile nanosystem for protein and peptide delivery.

PubMed

Singh, Deependra; Dubey, Pooja; Pradhan, Madhulika; Singh, Manju Rawat

2013-02-01

Proteins and peptides have been established to be the potential drug candidate for various human diseases. But, delivery of these therapeutic protein and peptides is still a challenge due to their several unfavorable properties. Nanotechnology is expanding as a promising tool for the efficient delivery of proteins and peptides. Among numerous nano-based carriers, ceramic nanoparticles have proven themselves as a unique carrier for protein and peptide delivery as they provide a more stable, bioavailable, readily manufacturable, and acceptable proteins and polypeptide formulation. This article provides an overview of the various aspects of ceramic nanoparticles including their classification, methods of preparation, latest advances, and applications as protein and peptide delivery carriers. Ceramic nanocarriers seem to have potential for preserving structural integrity of proteins and peptides, thereby promoting a better therapeutic effect. This approach thus provides pharmaceutical scientists with a new hope for the delivery of proteins and peptides. Still, considerable study on ceramic nanocarrier is necessary with respect to pharmacokinetics, toxicology, and animal studies to confirm their efficiency as well as safety and to establish their clinical usefulness and scale-up to industrial level.

Sturge-Weber syndrome: ear, nose, and throat issues and neurologic status.

PubMed

Irving, Natasha D; Lim, Jae Hyung; Cohen, Bernard; Ferenc, Lisa M; Comi, Anne M

2010-10-01

The pathophysiology of Sturge-Weber syndrome is poorly understood, and ear, nose, and throat involvement is possible. These issues can result in frequent illnesses or airway obstruction, affecting patients' neurologic status. Patients with definite brain involvement who reported potential ear, nose, and throat issues on intake questionnaires underwent retrospective reviews of their medical records. We examined the relationships between these issues, secondary surgical interventions, and patients' neurologic status. The most common complaints involved the sinuses and frequent ear infections. Six patients underwent placement of ear tubes, leading to improvements in migraines and stroke-like episodes in one patient, and improved seizure control in four others. Obstructive sleep apnea was confirmed in three patients who underwent sleep studies. Tonsil or adenoid removal occurred in another three patients. Surgery resulted in marked improvements regarding excessive drooling, daytime sleepiness, and breathing problems. These findings suggest that ear, nose, and throat problems occur frequently in patients with Sturge-Weber Syndrome, and when repeated ear infections are associated with uncontrolled seizures, early placement of ear tubes may be beneficial. Furthermore, patients with facial tissue hypertrophy may be at risk for obstructive sleep apnea, and should be appropriately evaluated. Copyright © 2010 Elsevier Inc. All rights reserved.

Towards a Chemiresistive Sensor-Integrated Electronic Nose: A Review

PubMed Central

Chiu, Shih-Wen; Tang, Kea-Tiong

2013-01-01

Electronic noses have potential applications in daily life, but are restricted by their bulky size and high price. This review focuses on the use of chemiresistive gas sensors, metal-oxide semiconductor gas sensors and conductive polymer gas sensors in an electronic nose for system integration to reduce size and cost. The review covers the system design considerations and the complementary metal-oxide-semiconductor integrated technology for a chemiresistive gas sensor electronic nose, including the integrated sensor array, its readout interface, and pattern recognition hardware. In addition, the state-of-the-art technology integrated in the electronic nose is also presented, such as the sensing front-end chip, electronic nose signal processing chip, and the electronic nose system-on-chip. PMID:24152879

Zein-based Nanocarriers as Potential Natural Alternatives for Drug and Gene Delivery: Focus on Cancer Therapy.

PubMed

Elzoghby, Ahmed; Freag, May; Mamdouh, Hadeer; Elkhodairy, Kadria

2017-01-01

Protein nanocarriers possess unique merits including minimal cytotoxicity, numerous renewable sources, and high drug-binding capability. In opposition to delivery carriers utilizing hydrophilic animal proteins, hydrophobic plant proteins (e.g, zein) have great tendency in fabricating controlled-release particulate carriers without additional chemical modification to stiffen them, which in turn evades the use of toxic chemical crosslinkers. Moreover, zein is related to a class of alcohol-soluble prolamins and generally recognized as safe (GRAS) carrier for drug delivery. Various techniques have been adopted to fabricate zein-based nanoparticulate systems including phase separation coacervation, spray-drying, supercritical anti-solvent approach, electrospinning and self-assembly. This manuscript reviews the recent advances in the zein-based colloidal nano-carrier systems such as nanospheres, nanocapsules, micelles and nanofibers with a special focus on their physicochemical characteristics and drug delivery applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Advances in the use of nanocarriers for cancer diagnosis and treatment

PubMed Central

Vieira, Débora Braga; Gamarra, Lionel Fernel

2016-01-01

ABSTRACT The use of nanocarriers as drug delivery systems for therapeutic or imaging agents can improve the pharmacological properties of commonly used compounds in cancer diagnosis and treatment. Advances in the surface engineering of nanoparticles to accommodate targeting ligands turned nanocarriers attractive candidates for future work involving targeted drug delivery. Although not targeted, several nanocarriers have been approved for clinical use and they are currently used to treat and/or diagnosis various types of cancers. Furthermore, there are several formulations, which are now in various stages of clinical trials. This review examined some approved formulations and discussed the advantages of using nanocarriers in cancer therapy. PMID:27074238

Chirality-dependent cellular uptake of chiral nanocarriers and intracellular delivery of different amounts of guest molecules

NASA Astrophysics Data System (ADS)

Kehr, Nermin Seda; Jose, Joachim

2017-12-01

We demonstrate the organic molecules loaded and chiral polymers coated periodic mesoporous organosilica (PMO) to generate chiral nanocarriers that we used to study chirality-dependent cellular uptake in serum and serum-free media and the subsequent delivery of different amounts of organic molecules into cells. Our results show that the amount of internalized PMO and thus the transported amount of organic molecules by nanocarrier PMO into cells was chirality dependent and controlled by hard/soft protein corona formation on the PMO surfaces. Therefore, this study demonstrate that chiral porous nanocarriers could potentially be used as advanced drug delivery systems which are able to use the specific chiral surface-protein interactions to influence/control the amount of (bio)active molecules delivered to cells in drug delivery and/or imaging applications.

Rational design for multifunctional non-liposomal lipid-based nanocarriers for cancer management: theory to practice

PubMed Central

2013-01-01

Nanomedicines have gained more and more attention in cancer therapy thanks to their ability to enhance the tumour accumulation and the intracellular uptake of drugs while reducing their inactivation and toxicity. In parallel, nanocarriers have been successfully employed as diagnostic tools increasing imaging resolution holding great promises both in preclinical research and in clinical settings. Lipid-based nanocarriers are a class of biocompatible and biodegradable vehicles that provide advanced delivery of therapeutic and imaging agents, improving pharmacokinetic profile and safety. One of most promising engineering challenges is the design of innovative and versatile multifunctional targeted nanotechnologies for cancer treatment and diagnosis. This review aims to highlight rational approaches to design multifunctional non liposomal lipid-based nanocarriers providing an update of literature in this field. PMID:24564841

Effects of block copolymer properties on nanocarrier protection from in vivo clearance

PubMed Central

D’Addio, Suzanne M.; Saad, Walid; Ansell, Steven M.; Squiers, John J.; Adamson, Douglas; Herrera-Alonso, Margarita; Wohl, Adam R.; Hoye, Thomas R.; Macosko, Christopher W.; Mayer, Lawrence D.; Vauthier, Christine; Prud’homme, Robert K.

2012-01-01

Drug nanocarrier clearance by the immune system must be minimized to achieve targeted delivery to pathological tissues. There is considerable interest in finding in vitro tests that can predict in vivo clearance outcomes. In this work, we produce nanocarriers with dense PEG layers resulting from block copolymer-directed assembly during rapid precipitation. Nanocarriers are formed using block copolymers with hydrophobic blocks of polystyrene (PS), poly-ε-caprolactone (PCL), poly-D,L-lactide (PLA), or poly-lactide-co-glycolide (PLGA), and hydrophilic blocks of polyethylene glycol (PEG) with molecular weights from 1.5 kg/mol to 9 kg/mol. Nanocarriers with paclitaxel prodrugs are evaluated in vivo in Foxn1nu mice to determine relative rates of clearance. The amount of nanocarrier in circulation after 4 h varies from 10% to 85% of initial dose, depending on the block copolymer. In vitro complement activation assays are conducted in an effort to correlate the protection of the nanocarrier surface from complement binding and activation and in vivo circulation. Guidelines for optimizing block copolymer structure to maximize circulation of nanocarriers formed by rapid precipitation and directed assembly are proposed, relating to the relative size of the hydrophilic and hydrophobic block, the hydrophobicity of the anchoring block, the absolute size of the PEG block, and polymer crystallinity. The in vitro results distinguish between the poorly circulating PEG5k-PCL9k and the better circulating nanocarriers, but could not rank the better circulating nanocarriers in order of circulation time. Analysis of PEG surface packing on monodisperse 200 nm latex spheres indicates that the sizes of the hydrophobic PCL, PS, and PLA blocks are correlated with the PEG blob size, and possibly the clearance from circulation. Suggestions for next step in vitro measurements are made. PMID:22732478

Methodological Variability Using Electronic Nose Technology For Headspace Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Knobloch, Henri; Turner, Claire; Spooner, Andrew

Since the idea of electronic noses was published, numerous electronic nose (e-nose) developments and applications have been used in analyzing solid, liquid and gaseous samples in the food and automotive industry or for medical purposes. However, little is known about methodological pitfalls that might be associated with e-nose technology. Some of the methodological variation caused by changes in ambient temperature, using different filters and changes in mass flow rates are described. Reasons for a lack of stability and reproducibility are given, explaining why methodological variation influences sensor responses and why e-nose technology may not always be sufficiently robust for headspacemore » analysis. However, the potential of e-nose technology is also discussed.« less

When the Nose Doesn’t Know: Canine Olfactory Function Associated With Health, Management, and Potential Links to Microbiota

PubMed Central

Jenkins, Eileen K.; DeChant, Mallory T.; Perry, Erin B.

2018-01-01

The impact of health, management, and microbiota on olfactory function in canines has not been examined in review. The most important characteristic of the detection canine is its sense of smell. Olfactory receptors are primarily located on the ethmoturbinates of the nasal cavity. The vomeronasal organ is an additional site of odor detection that detects chemical signals that stimulate behavioral and/or physiological changes. Recent advances in the genetics of olfaction suggest that genetic changes, along with the unique anatomy and airflow of the canine nose, are responsible for the macrosmia of the species. Inflammation, alterations in blood flow and hydration, and systemic diseases alter olfaction and may impact working efficiency of detection canines. The scientific literature contains abundant information on the potential impact of pharmaceuticals on olfaction in humans, but only steroids, antibiotics, and anesthetic agents have been studied in the canine. Physical stressors including exercise, lack of conditioning, and high ambient temperature impact olfaction directly or indirectly in the canine. Dietary fat content, amount of food per meal, and timing of meals have been demonstrated to impact olfaction in mice and dogs. Gastrointestinal (GI) microbiota likely impacts olfaction via bidirectional communication between the GI tract and brain, and the microbiota is impacted by exercise, diet, and stress. The objective of this literature review is to discuss the specific effects of health, management, and microbiota shifts on olfactory performance in working canines. PMID:29651421

Multi-scale Observation of Biological Interactions of Nanocarriers: from Nano to Macro

PubMed Central

Jin, Su-Eon; Bae, Jin Woo; Hong, Seungpyo

2010-01-01

Microscopic observations have played a key role in recent advancements in nanotechnology-based biomedical sciences. In particular, multi-scale observation is necessary to fully understand the nano-bio interfaces where a large amount of unprecedented phenomena have been reported. This review describes how to address the physicochemical and biological interactions of nanocarriers within the biological environments using microscopic tools. The imaging techniques are categorized based on the size scale of detection. For observation of the nano-scale biological interactions of nanocarriers, we discuss atomic force microscopy (AFM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). For the micro to macro-scale (in vitro and in vivo) observation, we focus on confocal laser scanning microscopy (CLSM) as well as in vivo imaging systems such as magnetic resonance imaging (MRI), superconducting quantum interference devices (SQUIDs), and IVIS®. Additionally, recently developed combined techniques such as AFM-CLSM, correlative Light and Electron Microscopy (CLEM), and SEM-spectroscopy are also discussed. In this review, we describe how each technique helps elucidate certain physicochemical and biological activities of nanocarriers such as dendrimers, polymers, liposomes, and polymeric/inorganic nanoparticles, thus providing a toolbox for bioengineers, pharmaceutical scientists, biologists, and research clinicians. PMID:20232368

An improved approach to identify irradiated spices using electronic nose, FTIR, and EPR spectroscopy.

PubMed

Sanyal, Bhaskar; Ahn, Jae-Jun; Maeng, Jeong-Hwan; Kyung, Hyun-Kyu; Lim, Ha-Kyeong; Sharma, Arun; Kwon, Joong-Ho

2014-09-01

Changes in cumin and chili powder from India resulting from electron-beam irradiation were investigated using 3 analytical methods: electronic nose (E-nose), Fourier transform infrared (FTIR) spectroscopy, and electron paramagnetic resonance (EPR) spectroscopy. The spices had been exposed to 6 to 14 kGy doses recommended for microbial decontamination. E-nose measured a clear difference in flavor patterns of the irradiated spices in comparison with the nonirradiated samples. Principal component analysis further showed a dose-dependent variation. FTIR spectra of the samples showed strong absorption bands at 3425, 3007 to 2854, and 1746 cm(-1). However, both nonirradiated and irradiated spice samples had comparable patterns without any noteworthy changes in functional groups. EPR spectroscopy of the irradiated samples showed a radiation-specific triplet signal at g = 2.006 with a hyper-fine coupling constant of 3 mT confirming the results obtained with the E-nose technique. Thus, E-nose was found to be a potential tool to identify irradiated spices. © 2014 Institute of Food Technologists®

Nose Surgery

MedlinePlus

... because of gravity, causing the sides of the nose to collapse inward, obstructing air flow. Mouth breathing or noisy and restricted breathing are common. Try lifting the tip of your nose to see if you breathe better. If so, ...

Promising approaches to circumvent the blood-brain barrier: progress, pitfalls and clinical prospects in brain cancer

PubMed Central

Papademetriou, Iason T; Porter, Tyrone

2015-01-01

Brain drug delivery is a major challenge for therapy of central nervous system (CNS) diseases. Biochemical modifications of drugs or drug nanocarriers, methods of local delivery, and blood–brain barrier (BBB) disruption with focused ultrasound and microbubbles are promising approaches which enhance transport or bypass the BBB. These approaches are discussed in the context of brain cancer as an example in CNS drug development. Targeting to receptors enabling transport across the BBB offers noninvasive delivery of small molecule and biological cancer therapeutics. Local delivery methods enable high dose delivery while avoiding systemic exposure. BBB disruption with focused ultrasound and microbubbles offers local and noninvasive treatment. Clinical trials show the prospects of these technologies and point to challenges for the future. PMID:26488496

Promising approaches to circumvent the blood-brain barrier: progress, pitfalls and clinical prospects in brain cancer.

PubMed

Papademetriou, Iason T; Porter, Tyrone

2015-01-01

Brain drug delivery is a major challenge for therapy of central nervous system (CNS) diseases. Biochemical modifications of drugs or drug nanocarriers, methods of local delivery, and blood-brain barrier (BBB) disruption with focused ultrasound and microbubbles are promising approaches which enhance transport or bypass the BBB. These approaches are discussed in the context of brain cancer as an example in CNS drug development. Targeting to receptors enabling transport across the BBB offers noninvasive delivery of small molecule and biological cancer therapeutics. Local delivery methods enable high dose delivery while avoiding systemic exposure. BBB disruption with focused ultrasound and microbubbles offers local and noninvasive treatment. Clinical trials show the prospects of these technologies and point to challenges for the future.

Stimuli-responsive polymeric nanocarriers for the controlled transport of active compounds: concepts and applications.

PubMed

Fleige, Emanuel; Quadir, Mohiuddin A; Haag, Rainer

2012-06-15

The use of polymeric nanocarriers to transport active compounds like small-molecular drugs, peptides, or genes found an increased attention throughout the different fields of natural sciences. Not only that these nanocarriers enhance the properties of already existing drugs in terms of solubility, bioavailability, and prolonged circulation times, furthermore they can be tailor-made in such a manner that they selectively release their cargo at the desired site of action. For the triggered release, these so-called smart drug delivery systems are designed to react on certain stimuli like pH, temperature, redox potential, enzymes, light, and ultrasound. Some of these stimuli are naturally occurring in vivo, for example the difference in pH in different cellular compartments while others are caused by the disease, which is to be treated, like differences in pH and temperature in some tumor tissues. Other external applied stimuli, like light and ultrasound, allow the temporal and spatial control of the release, since they are not triggered by any biological event. This review gives a brief overview about some types of stimuli-responsive nanocarriers with the main focus on organic polymer-based systems. Furthermore, the different stimuli and the design of corresponding responsive nanocarriers will be discussed with the help of selected examples from the literature. Copyright © 2012 Elsevier B.V. All rights reserved.

Exosomes as nanocarriers for immunotherapy of cancer and inflammatory diseases.

PubMed

Tran, Thanh-Huyen; Mattheolabakis, George; Aldawsari, Hibah; Amiji, Mansoor

2015-09-01

Cell secreted exosomes (30-100nm vesicles) play a major role in intercellular communication due to their ability to transfer proteins and nucleic acids from one cell to another. Depending on the originating cell type and the cargo, exosomes can have immunosuppressive or immunostimulatory effects, which have potential application as immunotherapies for cancer and autoimmune diseases. Cellular components shed from tumor cells or antigen presenting cells (APCs), such as dendritic cells, macrophages and B cells, have been shown to be efficiently packaged in exosomes. In this review, we focus on the application of exosomes as nanocarriers and immunological agents for cancer and autoimmune immunotherapy. APC-derived exosomes demonstrate effective therapeutic efficacy for the treatment of cancer and experimental autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis. In addition to their intrinsic immunomodulating activity, exosomes have many advantages over conventional nanocarriers for drug and gene delivery. Copyright © 2015 Elsevier Inc. All rights reserved.

Association of Alpha Tocopherol and Ag Sulfadiazine Chitosan Oleate Nanocarriers in Bioactive Dressings Supporting Platelet Lysate Application to Skin Wounds.

PubMed

Bonferoni, Maria Cristina; Sandri, Giuseppina; Rossi, Silvia; Dellera, Eleonora; Invernizzi, Alessandro; Boselli, Cinzia; Cornaglia, Antonia Icaro; Del Fante, Claudia; Perotti, Cesare; Vigani, Barbara; Riva, Federica; Caramella, Carla; Ferrari, Franca

2018-02-09

Chitosan oleate was previously proposed to encapsulate in nanocarriers some poorly soluble molecules aimed to wound therapy, such as the anti-infective silver sulfadiazine, and the antioxidant α tocopherol. Because nanocarriers need a suitable formulation to be administered to wounds, in the present paper, these previously developed nanocarriers were loaded into freeze dried dressings based on chitosan glutamate. These were proposed as bioactive dressings aimed to support the application to wounds of platelet lysate, a hemoderivative rich in growth factors. The dressings were characterized for hydration capacity, morphological aspect, and rheological and mechanical behavior. Although chitosan oleate nanocarriers clearly decreased the mechanical properties of dressings, these remained compatible with handling and application to wounds. Preliminary studies in vitro on fibroblast cell cultures demonstrated good compatibility of platelet lysate with nanocarriers and bioactive dressings. An in vivo study on a murine wound model showed an accelerating wound healing effect for the bioactive dressing and its suitability as support of the platelet lysate application to wounds.

Association of Alpha Tocopherol and Ag Sulfadiazine Chitosan Oleate Nanocarriers in Bioactive Dressings Supporting Platelet Lysate Application to Skin Wounds

PubMed Central

Bonferoni, Maria Cristina; Dellera, Eleonora; Invernizzi, Alessandro; Cornaglia, Antonia Icaro; Perotti, Cesare; Vigani, Barbara; Caramella, Carla; Ferrari, Franca

2018-01-01

Chitosan oleate was previously proposed to encapsulate in nanocarriers some poorly soluble molecules aimed to wound therapy, such as the anti-infective silver sulfadiazine, and the antioxidant α tocopherol. Because nanocarriers need a suitable formulation to be administered to wounds, in the present paper, these previously developed nanocarriers were loaded into freeze dried dressings based on chitosan glutamate. These were proposed as bioactive dressings aimed to support the application to wounds of platelet lysate, a hemoderivative rich in growth factors. The dressings were characterized for hydration capacity, morphological aspect, and rheological and mechanical behavior. Although chitosan oleate nanocarriers clearly decreased the mechanical properties of dressings, these remained compatible with handling and application to wounds. Preliminary studies in vitro on fibroblast cell cultures demonstrated good compatibility of platelet lysate with nanocarriers and bioactive dressings. An in vivo study on a murine wound model showed an accelerating wound healing effect for the bioactive dressing and its suitability as support of the platelet lysate application to wounds. PMID:29425164

Recent Advances in Endogenous and Exogenous Stimuli-Responsive Nanocarriers for Drug Delivery and Therapeutics.

PubMed

Hatakeyama, Hiroto

2017-01-01

Significant progress has been achieved in the development of stimuli-responsive nanocarriers for drug delivery, diagnosis, and therapy. Various types of triggers are utilized in the development of nanocarrier delivery. Endogenous factors such as changes in pH, redox, gradient, and enzyme concentration which are linked to disease progression have been utilized for controlling biodistribution and releasing drugs from nanocarriers, as well as increasing subsequent pharmacological activity at the disease site. Nanocarriers which respond to artificially-induced exogenous factors (such as temperature, light, magnetic field, and ultrasound) have also been developed. This review aims to discuss recent advances in the design of stimuli-responsive nanocarriers which appear to have a promising future in medicine.

Photoinduced PEG deshielding from ROS-sensitive linkage-bridged block copolymer-based nanocarriers for on-demand drug delivery.

PubMed

Li, Jie; Sun, Chunyang; Tao, Wei; Cao, Ziyang; Qian, Haisheng; Yang, Xianzhu; Wang, Jun

2018-07-01

Controlling poly(ethylene glycol) (PEG) shielding/deshielding at the desired site of action exhibits great advantages for nanocarrier-based on-demand drug delivery in vivo. However, the current PEG deshielding strategies were mainly designed for anticancer drug delivery; even so, their applications are also limited by tumor heterogeneity. As a proof-of-concept, we explored a photoinduced PEG deshielding nanocarrier TK-NP Ce6&PTX to circumvent the aforementioned challenge. The TK-NP Ce6&PTX encapsulating chlorin e6 (Ce6) and paclitaxel (PTX) was self-assembled from an innovative thioketal (TK) linkage-bridged diblock copolymer of PEG with poly(d,l-lactic acid) (PEG-TK-PLA). We demonstrated that the high PEGylation of TK-NP Ce6&PTX in blood helps the nanocarrier efficiently avoid rapid clearance and consequently prolongs its circulation time. At the desired site (tumor), 660-nm red light irradiation led to ROS generation in situ, which readily cleaved the TK linkage, resulting in PEG deshielding. Such photoinduced PEG deshielding at the desired site significantly enhances the cellular uptake of the nanocarriers, achieving on-demand drug delivery and superior therapeutic efficacy. More importantly, this strategy of photoinducing PEG deshielding of nanocarriers could potentially extend to a variety of therapeutic agents beyond anticancer drugs for on-demand delivery. Copyright © 2018 Elsevier Ltd. All rights reserved.

Smart conjugated polymer nanocarrier for healthy weight loss by negative feedback regulation of lipase activity

NASA Astrophysics Data System (ADS)

Chen, Yu-Lei; Zhu, Sha; Zhang, Lei; Feng, Pei-Jian; Yao, Xi-Kuang; Qian, Cheng-Gen; Zhang, Can; Jiang, Xi-Qun; Shen, Qun-Dong

2016-02-01

Healthy weight loss represents a real challenge when obesity is increasing in prevalence. Herein, we report a conjugated polymer nanocarrier for smart deactivation of lipase and thus balancing calorie intake. After oral administration, the nanocarrier is sensitive to lipase in the digestive tract and releases orlistat, which deactivates the enzyme and inhibits fat digestion. It also creates negative feedback to control the release of itself. The nanocarrier smartly regulates activity of the lipase cyclically varied between high and low levels. In spite of high fat diet intervention, obese mice receiving a single dose of the nanocarrier lose weight over eight days, whereas a control group continues the tendency to gain weight. Daily intragastric administration of the nanocarrier leads to lower weight of livers or fat pads, smaller adipocyte size, and lower total cholesterol level than that of the control group. Near-infrared fluorescence of the nanocarrier reveals its biodistribution.Healthy weight loss represents a real challenge when obesity is increasing in prevalence. Herein, we report a conjugated polymer nanocarrier for smart deactivation of lipase and thus balancing calorie intake. After oral administration, the nanocarrier is sensitive to lipase in the digestive tract and releases orlistat, which deactivates the enzyme and inhibits fat digestion. It also creates negative feedback to control the release of itself. The nanocarrier smartly regulates activity of the lipase cyclically varied between high and low levels. In spite of high fat diet intervention, obese mice receiving a single dose of the nanocarrier lose weight over eight days, whereas a control group continues the tendency to gain weight. Daily intragastric administration of the nanocarrier leads to lower weight of livers or fat pads, smaller adipocyte size, and lower total cholesterol level than that of the control group. Near-infrared fluorescence of the nanocarrier reveals its biodistribution

Recent Developments of Liposomes as Nanocarriers for Theranostic Applications

PubMed Central

Xing, Hang; Hwang, Kevin; Lu, Yi

2016-01-01

Liposomes are nanocarriers comprised of lipid bilayers encapsulating an aqueous core. The ability of liposomes to encapsulate a wide variety of diagnostic and therapeutic agents has led to significant interest in utilizing liposomes as nanocarriers for theranostic applications. In this review, we highlight recent progress in developing liposomes as nanocarriers for a) diagnostic applications to detect proteins, DNA, and small molecule targets using fluorescence, magnetic resonance, ultrasound, and nuclear imaging; b) therapeutic applications based on small molecule-based therapy, gene therapy and immunotherapy; and c) theranostic applications for simultaneous detection and treatment of heavy metal toxicity and cancers. In addition, we summarize recent studies towards understanding of interactions between liposomes and biological components. Finally, perspectives on future directions in advancing the field for clinical translations are also discussed. PMID:27375783

Nanocarriers in therapy of infectious and inflammatory diseases

NASA Astrophysics Data System (ADS)

Ikoba, Ufuoma; Peng, Haisheng; Li, Haichun; Miller, Cathy; Yu, Chenxu; Wang, Qun

2015-02-01

Nanotechnology is a growing science that has applications in various areas of medicine. The composition of nanocarriers for drug delivery is critical to guarantee high therapeutic performance when targeting specific host sites. Applications of nanotechnology are prevalent in the diagnosis and treatment of infectious and inflammatory diseases. This review summarizes recent advancements in the application of nanotechnology to the therapy of infectious and inflammatory diseases. The major focus is on the design and fabrication of various nanomaterials, characteristics and physicochemical properties of drug-loaded nanocarriers, and the use of these nanoscale drug delivery systems in treating infectious and inflammatory diseases, such as AIDS, hepatitis, tuberculosis, melanoma, and representative inflammatory diseases. Clinical trials and future perspective of the use of nanocarriers are also discussed in detail. We hope that such a review will be valuable to researchers who are exploring nanoscale drug delivery systems for the treatment of specific infectious and inflammatory diseases.

Effective use of nanocarriers as drug delivery systems for the treatment of selected tumors

PubMed Central

Ullah, Izhar; Qureshi, Omer Salman; Mustapha, Omer; Shafique, Shumaila; Zeb, Alam

2017-01-01

Nanotechnology has recently gained increased attention for its capability to effectively diagnose and treat various tumors. Nanocarriers have been used to circumvent the problems associated with conventional antitumor drug delivery systems, including their nonspecificity, severe side effects, burst release and damaging the normal cells. Nanocarriers improve the bioavailability and therapeutic efficiency of antitumor drugs, while providing preferential accumulation at the target site. A number of nanocarriers have been developed; however, only a few of them are clinically approved for the delivery of antitumor drugs for their intended actions at the targeted sites. The present review is divided into three main parts: first part presents introduction of various nanocarriers and their relevance in the delivery of anticancer drugs, second part encompasses targeting mechanisms and surface functionalization on nanocarriers and third part covers the description of selected tumors, including breast, lungs, colorectal and pancreatic tumors, and applications of relative nanocarriers in these tumors. This review increases the understanding of tumor treatment with the promising use of nanotechnology. PMID:29042776

Curcumin Cocrystal Micelles-Multifunctional Nanocomposites for Management of Neurodegenerative Ailments.

PubMed

Desai, Preshita P; Patravale, Vandana B

2018-04-01

Curcumin, a potent antioxidant polyphenol with neuroprotective and antiamyloid activities, has significant potential in the treatment of neurodegenerative disorders such as Alzheimer's disease. However, its clinical translation is delayed due to poor bioavailability. For effective use of curcumin in Alzheimer's disease, it is imperative to increase its bioavailability with enhanced delivery at a therapeutic site that is, brain. With this objective, pharmaceutical cocrystals of curcumin were developed and incorporated in micellar nanocarriers for nose-to-brain delivery. For cocrystals, an antioxidant hydrophilic coformer was strategically selected using molecular modeling approach. The cocrystals were formulated using a planetary ball mill, and the process was optimized using 3 2 factorial design followed by characterization using differential scanning calorimetry, X-ray diffraction, and Fourier-transform infrared spectroscopy analysis. The cocrystal micelles exhibited globule size of 28.79 ± 0.86 nm. Further, curcumin cocrystal and co-crystal micelles exhibited a significantly low (p value <0.01) IC 50 concentration for antioxidant activity as compared to curcumin corroborating superior antioxidant performance. In vivo studies revealed about 1.7-fold absolute bioavailability of curcumin cocrystal micelles with C max of 1218.38 ± 58.11 ng/mL and showed significantly high brain distribution even beyond 6 hours of dosing. Thus, the studies confirmed enhanced bioavailability, higher brain uptake, retention, and delayed clearance with curcumin cocrystal micellar nanocarriers. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Effect of flow on endothelial endocytosis of nanocarriers targeted to ICAM-1.

PubMed

Bhowmick, Tridib; Berk, Erik; Cui, Xiumin; Muzykantov, Vladimir R; Muro, Silvia

2012-02-10

Delivery of drugs into the endothelium by nanocarriers targeted to endothelial determinants may improve treatment of vascular maladies. This is the case for intercellular adhesion molecule 1 (ICAM-1), a glycoprotein overexpressed on endothelial cells (ECs) in many pathologies. ICAM-1-targeted nanocarriers bind to and are internalized by ECs via a non-classical pathway, CAM-mediated endocytosis. In this work we studied the effects of endothelial adaptation to physiological flow on the endocytosis of model polymer nanocarriers targeted to ICAM-1 (anti-ICAM/NCs, ~180 nm diameter). Culturing established endothelial-like cells (EAhy926 cells) and primary human umbilical vein ECs (HUVECs) under 4 dyn/cm(2) laminar shear stress for 24 h resulted in flow adaptation: cell elongation and formation of actin stress fibers aligned to the flow direction. Fluorescence microscopy showed that flow-adapted cells internalized anti-ICAM/NCs under flow, although at slower rate versus non flow-adapted cells under static incubation (~35% reduction). Uptake was inhibited by amiloride, whereas marginally affected by filipin and cadaverine, implicating that CAM-endocytosis accounts for anti-ICAM/NC uptake under flow. Internalization under flow was more modestly affected by inhibiting protein kinase C, which regulates actin remodeling during CAM-endocytosis. Actin recruitment to stress fibers that maintain the cell shape under flow may delay uptake of anti-ICAM/NCs under this condition by interfering with actin reorganization needed for CAM-endocytosis. Electron microscopy revealed somewhat slow, yet effective endocytosis of anti-ICAM/NCs by pulmonary endothelium after i.v. injection in mice, similar to that of flow-adapted cell cultures: ~40% (30 min) and 80% (3 h) internalization. Similar to cell culture data, uptake was slightly faster in capillaries with lower shear stress. Further, LPS treatment accelerated internalization of anti-ICAM/NCs in mice. Therefore, regulation of endocytosis

Effect of flow on endothelial endocytosis of nanocarriers targeted to ICAM-1

PubMed Central

Bhowmick, Tridib; Berk, Erik; Cui, Xiumin; Muzykantov, Vladimir R.; Muro, Silvia

2011-01-01

Delivery of drugs into the endothelium by nanocarriers targeted to endothelial determinants may improve treatment of vascular maladies. This is the case for intercellular adhesion molecule 1 (ICAM-1), a glycoprotein overexpressed on endothelial cells (ECs) in many pathologies. ICAM-1-targeted nanocarriers bind to and are internalized by ECs via a non-classical pathway, CAM-mediated endocytosis. In this work we studied the effects of endothelial adaptation to physiological flow on the endocytosis of model polymer nanocarriers targeted to ICAM-1 (anti-ICAM/NCs, ~180-nm diameter). Culturing established endothelial-like cells (EAhy926 cells) and primary human umbilical vein ECs (HUVECs) under 4 dyn/cm2 laminar shear stress for 24 h resulted in flow adaptation: cell elongation and formation of actin stress fibers aligned to the flow direction. Fluorescence microscopy showed that flow-adapted cells internalized anti-ICAM/NCs under flow, although at slower rate versus non flow-adapted cells under static incubation (~35% reduction). Uptake was inhibited by amiloride, whereas marginally affected by filipin and cadaverine, implicating that CAM-endocytosis accounts for anti-ICAM/NC uptake under flow. Internalization under flow was more modestly affected by inhibiting protein kinase C, which regulates actin remodeling during CAM-endocytosis. Actin recruitment to stress fibers that maintain the cell shape under flow may delay uptake of anti-ICAM/NCs under this condition by interfering with actin reorganization needed for CAM-endocytosis. Electron microscopy revealed somewhat slow, yet effective endocytosis of anti-ICAM/NCs by pulmonary endothelium after i.v. injection in mice, similar to that of flow-adapted cell cultures: ~40% (30 min) and 80% (3 h) internalization. Similar to cell culture data, uptake was slightly faster in capillaries with lower shear stress. Further, LPS treatment accelerated internalization of anti-ICAM/NCs in mice. Therefore, regulation of endocytosis of

Can odors of TCM be captured by electronic nose? The novel quality control method for musk by electronic nose coupled with chemometrics.

PubMed

Ye, Tao; Jin, Cheng; Zhou, Jian; Li, Xingfeng; Wang, Haitao; Deng, Pingye; Yang, Ying; Wu, Yanwen; Xiao, Xiaohe

2011-07-15

Musk is a precious and wide applied material in traditional Chinese medicine, also, an important material for the perfume industry all over the world. To establish a rapid, cost-effective and relatively objective assessment for the quality of musk, different musk samples, including authentic, fake and adulterate, were collected. A oxide sensor based electronic nose (E-nose) was employed to measure the musk samples, the E-nose generated data were analyzed by principal component analysis (PCA), the responses of 18 sensors of E-nose were evaluated by loading analysis. Results showed that a rapid evaluation of complex response of the samples could be obtained, in combination with PCA and the perception level of the E-nose was given better results in the recognition values of the musk aroma. The authentic, fake and adulterate musk could be distinguished by E-nose coupled with PCA, sensor 2, 3, 5, 12, 15 and 17 were found to be able to better discriminate between musk samples, confirming the potential application of an electronic instrument coupled with chemometrics for a rapid and on-line quality control for the traditional medicines. Copyright © 2011 Elsevier B.V. All rights reserved.

Nanocarriers for the Effective Treatment of Cervical Cancer: Research Advancements and Patent Analysis.

PubMed

Akhtar, Nida; Pathak, Kamla

2018-04-02

Cervical cancer being the cancer of cervix is caused by the aberrant cell growth that acquires an ability to spread/ invade to other body parts as well. It has been reported to be the second most commonest cause of death and cancer as well among women. Based on the severity of the disease, treatment aspect needs to be explored more in order to overcome the limitations acquired by conventional treatment. Recently, nanocarriers based drug delivery systems including liposomes, nanofibres, metallic NPs, polymeric NPs, dendrimers, polymeric micelles, antibody-drug conjugates etc. have been explored to target and treat cervical cancer. This review highlights numerous recent research and patent reports as well on nanocarriers based systems. Patents viz US, EP and WIPO have been retrieved using sites www.uspto.gov/patft and www.freepatentsonline.com to collect literature on nanocarriers. Various research reports and patents revealed nanocarriers to be effective in treating cervical cancer and these carriers are observed to be safer than the conventional treatment. Nanocarriers results in transforming drug distribution that can overpower drug resistance. Further, nanocarriers based drug delivery systems can particularly target drugs to cellular, subcellular and tissue sites. By enhancing the drug's bioavailability at the desired site, these systems result in therapeutic benefits like enhanced safety and efficacy. Also, in combination with other treatment approaches like radiation, photothermal and gene therapy, nanocarriers are reported to be quite effective and can define novel strategies to combat cervical cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Polymer Self-Assembled Nanostructures as Innovative Drug Nanocarrier Platforms.

PubMed

Pippa, Natassa; Pispas, Stergios; Demetzos, Costas

2016-01-01

Polymer self-assembled nanostructures are used in pharmaceutical sciences as bioactive molecules' delivery systems for therapeutic and diagnostic purposes. Micelles, polyelectrolyte complexes, polymersomes, polymeric nanoparticles, nanogels and polymer grafted liposomes represent delivery vehicles that are marketed and/or under clinical development, as drug formulations. In this mini-review, these, recently appeared in the literature, innovative polymer drug nanocarrier platforms are discussed, starting from their technological development in the laboratory to their potential clinical use, through studies of their biophysics, thermodynamics, physical behavior, morphology, bio-mimicry, therapeutic efficacy and safety. The properties of an ideal drug delivery system are the structural control over size and shape of drug or imaging agent cargo/domain, biocompatibility, nontoxic polymer/ pendant functionality and the precise, nanoscale container and/or scaffolding properties with high drug or imaging agent capacity features. Self-assembled polymer nanostructures exhibit all these properties and could be considered as ideal drug nanocarriers through control of their size, structure and morphology, with the aid of a large variety of parameters, in vitro and in vivo. These modern trends reside at the interface of soft matter self-assembly and pharmaceutical sciences and the technologies for health. Great advantages related to basic science and applications are expected by understanding the self-assembly behavior of these polymeric nanotechnological drug delivery systems, created through bio-inspiration and biomimicry and have potential utilization into clinical applications.

Dendritic Core-Multishell Nanocarriers in Murine Models of Healthy and Atopic Skin

NASA Astrophysics Data System (ADS)

Radbruch, Moritz; Pischon, Hannah; Ostrowski, Anja; Volz, Pierre; Brodwolf, Robert; Neumann, Falko; Unbehauen, Michael; Kleuser, Burkhard; Haag, Rainer; Ma, Nan; Alexiev, Ulrike; Mundhenk, Lars; Gruber, Achim D.

2017-01-01

Dendritic hPG-amid-C18-mPEG core-multishell nanocarriers (CMS) represent a novel class of unimolecular micelles that hold great potential as drug transporters, e.g., to facilitate topical therapy in skin diseases. Atopic dermatitis is among the most common inflammatory skin disorders with complex barrier alterations which may affect the efficacy of topical treatment.

The average Indian female nose.

PubMed

Patil, Surendra B; Kale, Satish M; Jaiswal, Sumeet; Khare, Nishant; Math, Mahantesh

2011-12-01

This study aimed to delineate the anthropometric measurements of the noses of young women of an Indian population and to compare them with the published ideals and average measurements for white women. This anthropometric survey included a volunteer sample of 100 young Indian women ages 18 to 35 years with Indian parents and no history of previous surgery or trauma to the nose. Standardized frontal, lateral, oblique, and basal photographs of the subjects' noses were taken, and 12 standard anthropometric measurements of the nose were determined. The results were compared with published standards for North American white women. In addition, nine nasal indices were calculated and compared with the standards for North American white women. The nose of Indian women differs significantly from the white nose. All the nasal measurements for the Indian women were found to be significantly different from those for North American white women. Seven of the nine nasal indices also differed significantly. Anthropometric analysis suggests differences between the Indian female nose and the North American white nose. Thus, a single aesthetic ideal is inadequate. Noses of Indian women are smaller and wider, with a less projected and rounded tip than the noses of white women. This study established the nasal anthropometric norms for nasal parameters, which will serve as a guide for cosmetic and reconstructive surgery in Indian women.

Polysaccharide-based micro/nanocarriers for oral colon-targeted drug delivery.

PubMed

Zhang, Lin; Sang, Yuan; Feng, Jing; Li, Zhaoming; Zhao, Aili

2016-08-01

Oral colon-targeted drug delivery has attracted many researchers because of its distinct advantages of increasing the bioavailability of the drug at the target site and reducing the side effects. Polysaccharides that are precisely activated by the physiological environment of the colon hold greater promise for colon targeting. Considerable research efforts have been directed towards developing polysaccharide-based micro/nanocarriers. Types of polysaccharides for colon targeting and in vitro/in vivo assessments of polysaccharide-based carriers for oral colon-targeted drug delivery are summarised. Polysaccharide-based microspheres have gained increased importance not just for the delivery of the drugs for the treatment of local diseases associated with the colon (colon cancer, inflammatory bowel disease (IBD), amoebiasis and irritable bowel syndrome (IBS)), but also for it's potential for the delivery of anti-rheumatoid arthritis and anti-chronic stable angina drugs. Besides, Polysaccharide-based micro/nanocarriers such as microbeads, microcapsules, microparticles, nanoparticles, nanogels and nanospheres are also introduced in this review.

Real-time particle tracking for studying intracellular trafficking of pharmaceutical nanocarriers.

PubMed

Huang, Feiran; Watson, Erin; Dempsey, Christopher; Suh, Junghae

2013-01-01

Real-time particle tracking is a technique that combines fluorescence microscopy with object tracking and computing and can be used to extract quantitative transport parameters for small particles inside cells. Since the success of a nanocarrier can often be determined by how effectively it delivers cargo to the target organelle, understanding the complex intracellular transport of pharmaceutical nanocarriers is critical. Real-time particle tracking provides insight into the dynamics of the intracellular behavior of nanoparticles, which may lead to significant improvements in the design and development of novel delivery systems. Unfortunately, this technique is not often fully understood, limiting its implementation by researchers in the field of nanomedicine. In this chapter, one of the most complicated aspects of particle tracking, the mean square displacement (MSD) calculation, is explained in a simple manner designed for the novice particle tracker. Pseudo code for performing the MSD calculation in MATLAB is also provided. This chapter contains clear and comprehensive instructions for a series of basic procedures in the technique of particle tracking. Instructions for performing confocal microscopy of nanoparticle samples are provided, and two methods of determining particle trajectories that do not require commercial particle-tracking software are provided. Trajectory analysis and determination of the tracking resolution are also explained. By providing comprehensive instructions needed to perform particle-tracking experiments, this chapter will enable researchers to gain new insight into the intracellular dynamics of nanocarriers, potentially leading to the development of more effective and intelligent therapeutic delivery vectors.

Accelerated blood clearance phenomenon upon cross-administration of PEGylated nanocarriers in beagle dogs

PubMed Central

Wang, Chunling; Cheng, Xiaobo; Su, Yuqing; Pei, Ying; Song, Yanzhi; Jiao, Jiao; Huang, Zhenjun; Ma, Yanfei; Dong, Yinming; Yao, Ying; Fan, Jingjing; Ta, Han; Liu, Xinrong; Xu, Hui; Deng, Yihui

2015-01-01

The cross-administration of nanocarriers modified by poly(ethylene glycol) (PEG), named PEGylated nanocarriers, a type of combination therapy, is becoming an increasingly important method of long-term drug delivery, to decrease side effects, avoid multidrug resistance, and increase therapeutic efficacy. However, repeated injections of PEGylated nanocarriers induces the accelerated blood clearance (ABC) phenomenon, prevents long circulation, and can cause adverse effects owing to alterations in the biodistribution of the drug. Although the nature of the ABC phenomenon that is induced by repeated injections of PEGylated nanocarriers has already been studied in detail, there are few reports on the immune response elicited by the cross-administration of PEGylated nanocarriers. In this study, we investigated the ABC phenomenon induced by the intravenous cross-administration of various PEGylated nanocarriers, including PEGylated liposomes (PL), PEG micelles (PM), PEGylated solid lipid nanoparticles (PSLN), and PEGylated emulsions (PE), in beagle dogs. The results indicated that the magnitude of the immune response elicited by the cross-administration was in the following order (from the strongest to the weakest): PL, PE, PSLN, PM. It is specifically PEG in the brush structure that elicits a significant immune response, in both the induction phase and the effectuation phase. Furthermore, the present study suggests that there is a considerable difference between the effect of repeated injections and cross-administration, depending on the colloidal structure. This work is a preliminary investigation into the cross-administration of PEGylated nanocarriers, and our observations can have serious implications for the design of combination therapies that use PEGylated vectors. PMID:25999716

Synergistic Interplay of Medicinal Chemistry and Formulation Strategies in Nanotechnology - From Drug Discovery to Nanocarrier Design and Development.

PubMed

Sunoqrot, Suhair; Hamed, Rania; Abdel-Halim, Heba; Tarawneh, Ola

2017-01-01

Over the last few decades, nanotechnology has given rise to promising new therapies and diagnostic tools for a wide range of diseases, especially cancer. The unique properties of nanocarriers such as liposomes, polymeric nanoparticles, micelles, and bioconjugates have mainly been exploited to enhance drug solubility, dissolution, and bioavailability. The most important advantage offered by nanotechnology is the ability to specifically target organs, tissues, and individual cells, which ultimately reduces the systemic side effects and improves the therapeutic index of drug molecules. The contribution of medicinal chemistry to nanotechnology is evident in the abundance of new active molecules that are being discovered but are faced with tremendous delivery challenges by conventional formulation strategies. Additionally, medicinal chemistry plays a crucial role in all the steps involved in the preparation of nanocarriers, where structure-activity relationships of the drug molecule as well as the nanocarrier are harnessed to enhance the design, efficacy, and safety of nanoformulations. The aim of this review is to provide an overview of the contributions of medicinal chemistry to nanotechnology, from supplying drug candidates and inspiring high-throughput nanocarrier design strategies, to structure-activity relationship elucidation and construction of computational models for better understanding of nanocarrier physicochemical properties and biological behavior. These two fields are undoubtedly interconnected and we will continue to see the fruits of that communion for years to come. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

DPPC/poly(2-methyl-2-oxazoline)-grad-poly(2-phenyl-2-oxazoline) chimeric nanostructures as potential drug nanocarriers

NASA Astrophysics Data System (ADS)

Pippa, Natassa; Kaditi, Eleni; Pispas, Stergios; Demetzos, Costas

2013-06-01

In this study, we report on the self assembly behavior and on stability studies of mixed (chimeric) nanosystems consisting of dipalmitoylphosphatidylcholine (DPPC) and poly(2-methyl-2-oxazoline)-grad-poly(2-phenyl-2-oxazoline) (MPOx) gradient copolymer in aqueous media and in fetal bovine serum (FBS). A gamut of light scattering techniques and fluorescence spectroscopy were used in order to extract information on the size and morphological characteristics of the nanoassemblies formed, as a function of gradient block copolymer content, as well as temperature. The hydrodynamic radii ( R h) of nanoassemblies decreased in the process of heating up to 50 °C, while the fractal dimension ( d f) values, also increased. Indomethacin was successfully incorporated into these chimeric nanocarriers. Drug release was depended on the components ratio. The present studies show that there are a number of parameters that can be used in order to alter the properties of chimeric nanosystems, and this is advantageous to the development of "smart" nanocarriers for drug delivery.

Resveratrol-Loaded Lipid Nanocarriers: Correlation between In Vitro Occlusion Factor and In Vivo Skin Hydrating Effect

PubMed Central

Parenti, Carmela; Turnaturi, Rita

2017-01-01

Lipid nanocarriers show occlusive properties that may be related to their ability to improve skin hydration. The aim of this work was to evaluate the relationship between in vitro occlusion factor and in vivo skin hydration for three types of lipid nanocarriers: nanoemulsions (NEs), solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs). These lipid nanocarriers were loaded with trans-resveratrol (RSV) and incorporated in gel vehicles. In vitro occlusion factor was in the order SLNs > NLCs > NEs. Gels containing unloaded or RSV loaded lipid nanocarriers were applied on the back of a hand of 12 healthy volunteers twice a day for one week, recording skin hydration changes using the instrument Soft Plus. An increase of skin hydration was observed for all lipid nanocarriers (SLNs > NLCs > NEs). RSV loading into these nanocarriers did not affect in vitro and in vivo lipid nanocarriers effects. A linear relationship (r2 = 0.969) was observed between occlusion factor and in vivo increase of skin hydration. Therefore, the results of this study showed the feasibility of using the occlusion factor to predict in vivo skin hydration resulting from topical application of different lipid nanocarriers loading an active ingredient with no inherent hydrating activity. PMID:29232856

Self-assembled penetratin-deferasirox micelles as potential carriers for hydrophobic drug delivery.

PubMed

Goswami, Dibakar; Vitorino, Hector Aguilar; Machini, M Teresa; Espósito, Breno P

2015-11-01

There has been a growing interest in the use of micelles with nanofiber geometry as nanocarriers for hydrophobic drugs. Here we show that the conjugate of penetratin, a cell-penetrating peptide (CPP) with blood-brain barrier (BBB) permeability, and deferasirox (DFX), a hydrophobic iron chelator, self-assembles to form micelles at a very low concentration (∼15 mg/L). The critical micelle concentration (CMC) was determined, and the micelles were used for solubilizing curcumin, a hydrophobic anti-neurodegenerative drug, for successful delivery across RBE4 cells, a BBB model. Transmission Electron Microscope images of the curcumin-loaded micelles confirmed the formation of nanofibers. These results indicate the potential of CPP-drug conjugates for use as nanocarriers. © 2015 Wiley Periodicals, Inc.

Electronic noses and tongues: Applications for the food and pharmaceutical industries

USDA-ARS?s Scientific Manuscript database

The electronic nose (enose) is designed to crudely mimic the human brain in that most contain sensors that non-selectively interact with odor molecules to produce some sort of signal that is then sent to a computer that uses multivariate statistics to determine patterns in the data. This pattern rec...

Nanocarriers for delivery of siRNA and co-delivery of siRNA and other therapeutic agents.

PubMed

Zhao, Jing; Feng, Si-Shen

2015-07-01

A major problem in cancer treatment is the multidrug resistance. siRNA inhibitors have great advantages to solve the problem, if the bottleneck of their delivery could be well addressed by the various nanocarriers. Moreover, co-delivery of siRNA together with the various anticancer agents in one nanocarrier may maximize their additive or synergistic effect. This review provides a comprehensive summary on the state-of-the-art of the nanocarriers, which may include prodrugs, micelles, liposomes, dendrimers, nanohydrogels, solid lipid nanoparticles, nanoparticles of biodegradable polymers and nucleic acid nanocarriers for delivery of siRNA and co-delivery of siRNA together with anticancer agents with focus on synthesis of the nanocarrier materials, design and characterization, in vitro and in vivo evaluation, and prospect and challenges of nanocarriers.

A systematic review on nanoencapsulation of food bioactive ingredients and nutraceuticals by various nanocarriers.

PubMed

Assadpour, Elham; Jafari, Seid Mahdi

2018-06-08

Today, there is an ever-growing interest on natural food ingredients both by consumers and producers in the food industry. In fact, people are looking for those products in the market which are free from artificial and synthetic additives and can promote their health. These food bioactive ingredients should be formulated in such a way that protects them against harsh process and environmental conditions and safely could be delivered to the target organs and cells. Nanoencapsulation is a perfect strategy for this situation and there have been many studies in recent years for nanoencapsulation of food components and nutraceuticals by different technologies. In this review paper, our main goal is firstly to have an overview of nanoencapsulation techniques applicable to food ingredients in a systematic classification, i.e., lipid-based nanocarriers, nature-inspired nanocarriers, special-equipment-based nanocarriers, biopolymer nanocarriers, and other miscellaneous nanocarriers. Then, application of these cutting-edge nanocarriers for different nutraceuticals including phenolic compounds and antioxidants, natural food colorants, antimicrobial agents and essential oils, vitamins, minerals, flavors, fish oils and essential fatty acids will be discussed along with presenting some examples in each field.

Temperature-Responsive Smart Nanocarriers for Delivery Of Therapeutic Agents: Applications and Recent Advances.

PubMed

Karimi, Mahdi; Sahandi Zangabad, Parham; Ghasemi, Alireza; Amiri, Mohammad; Bahrami, Mohsen; Malekzad, Hedieh; Ghahramanzadeh Asl, Hadi; Mahdieh, Zahra; Bozorgomid, Mahnaz; Ghasemi, Amir; Rahmani Taji Boyuk, Mohammad Reza; Hamblin, Michael R

2016-08-24

Smart drug delivery systems (DDSs) have attracted the attention of many scientists, as carriers that can be stimulated by changes in environmental parameters such as temperature, pH, light, electromagnetic fields, mechanical forces, etc. These smart nanocarriers can release their cargo on demand when their target is reached and the stimulus is applied. Using the techniques of nanotechnology, these nanocarriers can be tailored to be target-specific, and exhibit delayed or controlled release of drugs. Temperature-responsive nanocarriers are one of most important groups of smart nanoparticles (NPs) that have been investigated during the past decades. Temperature can either act as an external stimulus when heat is applied from the outside, or can be internal when pathological lesions have a naturally elevated termperature. A low critical solution temperature (LCST) is a special feature of some polymeric materials, and most of the temperature-responsive nanocarriers have been designed based on this feature. In this review, we attempt to summarize recent efforts to prepare innovative temperature-responsive nanocarriers and discuss their novel applications.

Plant Pest Detection Using an Artificial Nose System: A Review.

PubMed

Cui, Shaoqing; Ling, Peter; Zhu, Heping; Keener, Harold M

2018-01-28

This paper reviews artificial intelligent noses (or electronic noses) as a fast and noninvasive approach for the diagnosis of insects and diseases that attack vegetables and fruit trees. The particular focus is on bacterial, fungal, and viral infections, and insect damage. Volatile organic compounds (VOCs) emitted from plants, which provide functional information about the plant's growth, defense, and health status, allow for the possibility of using noninvasive detection to monitor plants status. Electronic noses are comprised of a sensor array, signal conditioning circuit, and pattern recognition algorithms. Compared with traditional gas chromatography-mass spectrometry (GC-MS) techniques, electronic noses are noninvasive and can be a rapid, cost-effective option for several applications. However, using electronic noses for plant pest diagnosis is still in its early stages, and there are challenges regarding sensor performance, sampling and detection in open areas, and scaling up measurements. This review paper introduces each element of electronic nose systems, especially commonly used sensors and pattern recognition methods, along with their advantages and limitations. It includes a comprehensive comparison and summary of applications, possible challenges, and potential improvements of electronic nose systems for different plant pest diagnoses.

Current Progress of Virus-mimicking Nanocarriers for Drug Delivery

PubMed Central

Somiya, Masaharu; Liu, Qiushi; Kuroda, Shun'ichi

2017-01-01

Nanomedicines often involve the use of nanocarriers as a delivery system for drugs or genes for maximizing the therapeutic effect and/or minimizing the adverse effect. From drug administration to therapeutic activity, nanocarriers must evade the host's immune system, specifically and efficiently target and enter the cell, and release their payload into the cell cytoplasm by endosomal escape. These processes constitute the early infection stage of viruses. Viruses are a powerful natural nanomaterial for the efficient delivery of genetic information by sophisticated mechanisms. Over the past two decades, many virus-inspired nanocarriers have been generated to permit successful drug and gene delivery. In this review, we summarize the early infection machineries of viruses, of which the part has so far been utilized for delivery systems. Furthermore, we describe basics and applications of the bio-nanocapsule, which is a hepatitis B virus-mimicking nanoparticle harboring nearly all activities involved in the early infection machineries (i.e., stealth activity, targeting activity, cell entry activity, endosomal escaping activity). PMID:29188175

Evaluation of blood-brain barrier-stealth nanocomposites for in situ glioblastoma theranostics applications

NASA Astrophysics Data System (ADS)

Su, Chia-Hao; Tsai, Ching-Yi; Tomanek, Boguslaw; Chen, Wei-Yu; Cheng, Fong-Yu

2016-04-01

The blood-brain barrier (BBB) is a physiological structure of the blood vessels in the brain. The BBB efficiently traps most therapeutic drugs in the blood vessels and stops them from entering the brain tissue, resulting in a decreased therapeutic efficiency. In this study, we developed BBB-stealth nanocomposites composed of iron oxide (Fe3O4) nanoparticles (NPs) as a safe nanocarrier for glioblastoma therapy. We showed the antitumor activity of Dox/alg-Fe3O4 NPs using in vitro and in vivo tests. We demonstrated that G23-alg-Fe3O4 NPs crossed the BBB and entered the brain. In situ glioblastoma tumor-bearing mice were used to successfully evaluate the antitumor activity of G23-Dox/alg-Fe3O4 NPs. Magnetic resonance imaging (MRI) and bioluminescence imaging (BLI) confirmed the BBB crossing. The BBB-stealth nanocomposites show great potential for a proof-of-concept clinical trial as a theranostics platform for human brain tumor therapy.The blood-brain barrier (BBB) is a physiological structure of the blood vessels in the brain. The BBB efficiently traps most therapeutic drugs in the blood vessels and stops them from entering the brain tissue, resulting in a decreased therapeutic efficiency. In this study, we developed BBB-stealth nanocomposites composed of iron oxide (Fe3O4) nanoparticles (NPs) as a safe nanocarrier for glioblastoma therapy. We showed the antitumor activity of Dox/alg-Fe3O4 NPs using in vitro and in vivo tests. We demonstrated that G23-alg-Fe3O4 NPs crossed the BBB and entered the brain. In situ glioblastoma tumor-bearing mice were used to successfully evaluate the antitumor activity of G23-Dox/alg-Fe3O4 NPs. Magnetic resonance imaging (MRI) and bioluminescence imaging (BLI) confirmed the BBB crossing. The BBB-stealth nanocomposites show great potential for a proof-of-concept clinical trial as a theranostics platform for human brain tumor therapy. Electronic supplementary information (ESI) available: Experimental details. See DOI: 10.1039/c6nr00280c

Recent advances in hyaluronic acid-decorated nanocarriers for targeted cancer therapy

PubMed Central

Wickens, Jennifer M.; Alsaab, Hashem O.; Kesharwani, Prashant; Bhise, Ketki; Amin, Mohd Cairul Iqbal Mohd; Tekade, Rakesh Kumar; Gupta, Umesh; Iyer, Arun K.

2016-01-01

The cluster-determinant 44 (CD44) receptor has a high affinity for hyaluronic acid (HA) binding and is a desirable receptor for active targeting based on its overexpression in cancer cells compared with normal body cells. The nanocarrier affinity can be increased by conjugating drug-loaded carriers with HA, allowing enhanced cancer cell uptake via the HA-CD44 receptor-mediated endocytosis pathway. In this review, we discuss recent advances in HA-based nanocarriers and micelles for cancer therapy. In vitro and in vivo experiments have repeatedly indicated HA-based nanocarriers to be a target-specific drug and gene delivery platform with great promise for future applications in clinical cancer therapy. PMID:28017836

Recent advances in hyaluronic acid-decorated nanocarriers for targeted cancer therapy.

PubMed

Wickens, Jennifer M; Alsaab, Hashem O; Kesharwani, Prashant; Bhise, Ketki; Amin, Mohd Cairul Iqbal Mohd; Tekade, Rakesh Kumar; Gupta, Umesh; Iyer, Arun K

2017-04-01

The cluster-determinant 44 (CD44) receptor has a high affinity for hyaluronic acid (HA) binding and is a desirable receptor for active targeting based on its overexpression in cancer cells compared with normal body cells. The nanocarrier affinity can be increased by conjugating drug-loaded carriers with HA, allowing enhanced cancer cell uptake via the HA-CD44 receptor-mediated endocytosis pathway. In this review, we discuss recent advances in HA-based nanocarriers and micelles for cancer therapy. In vitro and in vivo experiments have repeatedly indicated HA-based nanocarriers to be a target-specific drug and gene delivery platform with great promise for future applications in clinical cancer therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Lysosomal enzyme delivery by ICAM-1-targeted nanocarriers bypassing glycosylation- and clathrin-dependent endocytosis.

PubMed

Muro, Silvia; Schuchman, Edward H; Muzykantov, Vladimir R

2006-01-01

Enzyme replacement therapy, a state-of-the-art treatment for many lysosomal storage disorders, relies on carbohydrate-mediated binding of recombinant enzymes to receptors that mediate lysosomal delivery via clathrin-dependent endocytosis. Suboptimal glycosylation of recombinant enzymes and deficiency of clathrin-mediated endocytosis in some lysosomal enzyme-deficient cells limit delivery and efficacy of enzyme replacement therapy for lysosomal disorders. We explored a novel delivery strategy utilizing nanocarriers targeted to a glycosylation- and clathrin-independent receptor, intercellular adhesion molecule (ICAM)-1, a glycoprotein expressed on diverse cell types, up-regulated and functionally involved in inflammation, a hallmark of many lysosomal disorders. We targeted recombinant human acid sphingomyelinase (ASM), deficient in types A and B Niemann-Pick disease, to ICAM-1 by loading this enzyme to nanocarriers coated with anti-ICAM. Anti-ICAM/ASM nanocarriers, but not control ASM or ASM nanocarriers, bound to ICAM-1-positive cells (activated endothelial cells and Niemann-Pick disease patient fibroblasts) via ICAM-1, in a glycosylation-independent manner. Anti-ICAM/ASM nanocarriers entered cells via CAM-mediated endocytosis, bypassing the clathrin-dependent pathway, and trafficked to lysosomes, where delivered ASM displayed stable activity and alleviated lysosomal lipid accumulation. Therefore, lysosomal enzyme targeting using nanocarriers targeted to ICAM-1 bypasses defunct pathways and may improve the efficacy of enzyme replacement therapy for lysosomal disorders, such as Niemann-Pick disease.

Why Does My Nose Run?

MedlinePlus

... Staying Safe Videos for Educators Search English Español Why Does My Nose Run? KidsHealth / For Kids / Why Does My Nose Run? ... out the whole story. What's Running? To understand why your nose runs, you need to know what mucus (say: MYOO- ...

Nanocarriers from GRAS Zein Proteins to Encapsulate Hydrophobic Actives.

PubMed

Weissmueller, Nikolas T; Lu, Hoang D; Hurley, Amanda; Prud'homme, Robert K

2016-11-14

One factor limiting the expansion of nanomedicines has been the high cost of the materials and processes required for their production. We present a continuous, scalable, low cost nanoencapsulation process, Flash Nanoprecipitation (FNP) that enables the production of nanocarriers (NCs) with a narrow size distribution using zein corn proteins. Zein is a low cost, GRAS protein (having the FDA status of "Generally Regarded as Safe") currently used in food applications, which acts as an effective encapsulant for hydrophobic compounds using FNP. The four-stream FNP configuration allows the encapsulation of very hydrophobic compounds in a way that is not possible with previous precipitation processes. We present the encapsulation of several model active compounds with as high as 45 wt % drug loading with respect to zein concentration into ∼100 nm nanocarriers. Three examples are presented: (1) the pro-drug antioxidant, vitamin E-acetate, (2) an anticholera quorum-sensing modulator CAI-1 ((S)-3-hydroxytridecan-4-one; CAI-1 that reduces Vibrio cholerae virulence by modulating cellular communication), and (3) hydrophobic fluorescent dyes with a range of hydrophobicities. The specific interaction between zein and the milk protein, sodium caseinate, provides stabilization of the NCs in PBS, LB medium, and in pH 2 solutions. The stability and size changes in the three media provide information on the mechanism of assembly of the zein/active/casein NC.

Lipopolysaccharide based oral nanocarriers for the improvement of bioavailability and anticancer efficacy of curcumin.

PubMed

Chaurasia, Sundeep; Patel, Ravi R; Chaubey, Pramila; Kumar, Nagendra; Khan, Gayasuddin; Mishra, Brahmeshwar

2015-10-05

Soluthin MD(®), a unique phosphatidylcholine-maltodextrin based hydrophilic lipopolysaccharide, which exhibits superior biocompatibility and bioavailability enhancer properties for poorly water soluble drug(s). Curcumin (CUR) is a potential natural anticancer drug with low bioavailability due to poor aqueous solubility. The study aims at formulation and optimization of CUR loaded lipopolysaccharide nanocarriers (C-LPNCs) to enhance oral bioavailability and anticancer efficacy in colon-26 tumor-bearing mice in vitro and in vivo. The Optimized C-LPNCs demonstrated favorable mean particle size (108 ± 3.4 nm) and percent entrapment efficiency (65.29 ± 1.0%). Pharmacokinetic parameters revealed ∼130-fold increase in oral bioavailability and cytotoxicity studies demonstrated ∼23-fold reduction in 50% cell growth inhibition when treated with optimized C-LPNCs as compared to pure CUR. In vivo anticancer study performed with optimized C-LPNCs showed significant increase in efficacy compared with pure CUR. Thus, lipopolysaccharide nanocarriers show potential delivery strategy to improve oral bioavailability and anticancer efficacy of CUR in the treatment of colorectal cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.

The straight truth: measuring observer attention to the crooked nose.

PubMed

Godoy, Andres; Ishii, Masaru; Byrne, Patrick J; Boahene, Kofi D O; Encarnacion, Carlos O; Ishii, Lisa E

2011-05-01

Quantify attentional distraction to crooked noses pre- and postoperatively as compared with normal noses by using an established metric of attention in a pilot study. Prospective, randomized, controlled experiment with crossover. An eye-tracker system was used to record the eye-movement patterns, called scanpaths, of 40 naive observers gazing at pictures of faces with crooked noses preoperatively or postoperatively and pictures of faces without a crooked nose included as "normals." The fixation durations within the nasal area for each group of faces presented were compared. A mixed-design univariate analysis of variance was performed to test the hypothesis that mean fixation times in the nasal region varied by face group. The results were highly statistically significant, F(2,116) = 20.28, P = .000, η(2) = 0.029. Marginal means were calculated for each nasal area of interest group with confidence intervals (normal, 2.32 [2.26-2.38]; preoperative, 2.66 [2.58-2.75]; postoperative, 2.43 [2.35-2.51]). Post hoc testing with Bonferroni correction for three comparisons showed differences between the normal and preoperative groups (χ(2) 41.38, P = .000) and between the preoperative and postoperative groups (χ(2) 14.41, P = .000) but not between the normal and postoperative groups (χ(2) 4.19, P = .12). There were highly statistically significant differences in attention paid to the nasal area of crooked noses preoperatively and postoperatively, and there were no differences in attention to the nasal area between the postoperative noses and the normal noses. This represents a novel method for objectively evaluating attention and success of surgical procedures to minimize the appearance of deformities. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

Different Ways to Apply a Measurement Instrument of E-Nose Type to Evaluate Ambient Air Quality with Respect to Odour Nuisance in a Vicinity of Municipal Processing Plants.

PubMed

Szulczyński, Bartosz; Wasilewski, Tomasz; Wojnowski, Wojciech; Majchrzak, Tomasz; Dymerski, Tomasz; Namieśnik, Jacek; Gębicki, Jacek

2017-11-19

This review paper presents different ways to apply a measurement instrument of e-nose type to evaluate ambient air with respect to detection of the odorants characterized by unpleasant odour in a vicinity of municipal processing plants. An emphasis was put on the following applications of the electronic nose instruments: monitoring networks, remote controlled robots and drones as well as portable devices. Moreover, this paper presents commercially available sensors utilized in the electronic noses and characterized by the limit of quantification below 1 ppm v / v , which is close to the odour threshold of some odorants. Additionally, information about bioelectronic noses being a possible alternative to electronic noses and their principle of operation and application potential in the field of air evaluation with respect to detection of the odorants characterized by unpleasant odour was provided.

Electronic Noses and Tongues in Wine Industry

PubMed Central

Rodríguez-Méndez, María L.; De Saja, José A.; González-Antón, Rocio; García-Hernández, Celia; Medina-Plaza, Cristina; García-Cabezón, Cristina; Martín-Pedrosa, Fernando

2016-01-01

The quality of wines is usually evaluated by a sensory panel formed of trained experts or traditional chemical analysis. Over the last few decades, electronic noses (e-noses) and electronic tongues have been developed to determine the quality of foods and beverages. They consist of arrays of sensors with cross-sensitivity, combined with pattern recognition software, which provide a fingerprint of the samples that can be used to discriminate or classify the samples. This holistic approach is inspired by the method used in mammals to recognize food through their senses. They have been widely applied to the analysis of wines, including quality control, aging control, or the detection of fraudulence, among others. In this paper, the current status of research and development in the field of e-noses and tongues applied to the analysis of wines is reviewed. Their potential applications in the wine industry are described. The review ends with a final comment about expected future developments. PMID:27826547

Polycaprolactone/maltodextrin nanocarrier for intracellular drug delivery: formulation, uptake mechanism, internalization kinetics, and subcellular localization.

PubMed

Korang-Yeboah, Maxwell; Gorantla, Yamini; Paulos, Simon A; Sharma, Pankaj; Chaudhary, Jaideep; Palaniappan, Ravi

2015-01-01

Prostate cancer (PCa) disease progression is associated with significant changes in intracellular and extracellular proteins, intracellular signaling mechanism, and cancer cell phenotype. These changes may have direct impact on the cellular interactions with nanocarriers; hence, there is the need for a much-detailed understanding, as nanocarrier cellular internalization and intracellular sorting mechanism correlate directly with bioavailability and clinical efficacy. In this study, we report the differences in the rate and mechanism of cellular internalization of a biocompatible polycaprolactone (PCL)/maltodextrin (MD) nanocarrier system for intracellular drug delivery in LNCaP, PC3, and DU145 PCa cell lines. PCL/MD nanocarriers were designed and characterized. PCL/MD nanocarriers significantly increased the intracellular concentration of coumarin-6 and fluorescein isothiocyanate-labeled bovine serum albumin, a model hydrophobic and large molecule, respectively. Fluorescence microscopy and flow cytometry analysis revealed rapid internalization of the nanocarrier. The extent of nanocarrier cellular internalization correlated directly with cell line aggressiveness. PCL/MD internalization was highest in PC3 followed by DU145 and LNCaP, respectively. Uptake in all PCa cell lines was metabolically dependent. Extraction of endogenous cholesterol by methyl-β-cyclodextrin reduced uptake by 75%±4.53% in PC3, 64%±6.01% in LNCaP, and 50%±4.50% in DU145, indicating the involvement of endogenous cholesterol in cellular internalization. Internalization of the nanocarrier in LNCaP was mediated mainly by macropinocytosis and clathrin-independent pathways, while internalization in PC3 and DU145 involved clathrin-mediated endocytosis, clathrin-independent pathways, and macropinocytosis. Fluorescence microscopy showed a very diffused and non-compartmentalized subcellular localization of the PCL/MD nanocarriers with possible intranuclear localization and minor colocalization in

Nanovaccines : nanocarriers for antigen delivery.

PubMed

Gonzalez-Aramundiz, Jose Vicente; Cordeiro, Ana Sara; Csaba, Nœmi; de la Fuente, Maria; Alonso, María José

2012-01-01

Vaccination has become one of the most important health interventions of our times, revolutionizing health care, and improving the quality of life and life expectancy of millions all over the world. In spite of this, vaccine research remains a vast field for innovation and improvement. Indeed, the shift towards the use of sub-unit antigens, much safer but less immunogenic, and the recognized need to facilitate the access to vaccines in the global framework is currently stimulating the search for safe and efficient adjuvants and delivery technologies. Within this context, nanocarriers have gained particular attention over the last years and appear as one of the most promising strategies for antigen delivery. A number of biomaterials and technologies can be used to design nanovaccines that fulfill the requirements of new vaccination approaches, such as single-dose and transmucosal immunization, critical for achieving a widespread coverage while reducing the overall costs in relation to traditional forms of vaccination. Here we present an overview of the current state of nanocarriers for antigen delivery, developed with the perspective of contributing to the global vaccination goal. © Société de Biologie, 2013.

Differential intra-endothelial delivery of polymer nanocarriers targeted to distinct PECAM-1 epitopes

PubMed Central

Garnacho, Carmen; Albelda, Steven M.; Muzykantov, Vladimir R.; Muro, Silvia

2008-01-01

Coupling drug carriers to antibodies for targeting endothelial cells (ECs) may improve treatment of vascular and pulmonary diseases. Selecting antibodies that deliver carriers to the cell surface or intracellularly may further optimize specifcity of interventions. We studied antibody-directed targeting of nanocarriers to platelet–endothelial cell adhesion molecule (PECAM)-1, an endothelial glycoprotein containing 6 Ig-like extracellular domains. PECAM-1 antibodies bind to ECs without internalization, but ECs internalize by endocytosis nanocarriers carrying multiple copies of anti-PECAM (anti-PECAM/NCs). To determine whether binding and intracellular transport of anti-PECAM/NCs depend on the epitope engaged, we targeted five PECAM-1 epitopes: mAb35, mAb37 and mAb62 (membrane-distal Ig domain 1), mAbGi34 (Ig domains 2/3), and mAb4G6 (membrane-proximal Ig domain 6). The antibodies bound to ECs regardless of the epitope proximity to the plasmalemma, whereas 130 nm diameter nanocarriers only targeted effectively distal domains (mAb4G6/NCs did not bind to ECs). ECs internalized mAb35, mAb62, and mAbGi34 carriers regardless of their size (0.13 to 5 µm diameter), yet they did not internalize mAb37/NCs. After internalization, mAb62/NCs trafficked to lysosomes within 2–3 h, whereas mAb35/NCs had prolonged residence in pre-lysosomal vesicles. Therefore, endothelial binding, endocytosis, and intracellular transport of anti-PECAM/NCs are epitope-specific. This paradigm will guide the design of endothelial drug delivery systems providing specific cellular localizations. PMID:18606202

Metal Oxide Sensors for Electronic Noses and Their Application to Food Analysis

PubMed Central

Berna, Amalia

2010-01-01

Electronic noses (E-noses) use various types of electronic gas sensors that have partial specificity. This review focuses on commercial and experimental E-noses that use metal oxide semi-conductors. The review covers quality control applications to food and beverages, including determination of freshness and identification of contaminants or adulteration. Applications of E-noses to a wide range of foods and beverages are considered, including: meat, fish, grains, alcoholic drinks, non-alcoholic drinks, fruits, milk and dairy products, olive oils, nuts, fresh vegetables and eggs. PMID:22319332

Metronomic chemotherapy and nanocarrier platforms.

PubMed

Abu Lila, Amr S; Ishida, Tatsuhiro

2017-08-01

The therapeutic concept of administering chemotherapeutic agents continuously at lower doses, relative to the maximum tolerated dose (MTD) without drug-free breaks over extended periods -known as "metronomic chemotherapy"- is a promising approach for anti-angiogenic cancer therapy. In comparison with MTD chemotherapy regimens, metronomic chemotherapy has demonstrated reduced toxicity. However, as a monotherapy, metronomic chemotherapy has failed to provide convincing results in clinical trials. Therapeutic approaches including combining the anti-angiogenic "metronomic" therapy with conventional radio-/chemo-therapy and/or targeted delivery of chemotherapeutic agents to tumor tissues via their encapsulation with nanocarrier-based platforms have proven to potentiate the overall therapeutic outcomes. In this review, therefore, we focused on the mutual contribution made by nanoscale drug delivery platforms to the therapeutic efficacy of metronomic-based chemotherapy. In addition, the influence that the dosing schedule has on the overall therapeutic efficacy of metronomic chemotherapy is discussed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Treatment outcomes of saddle nose correction.

PubMed

Hyun, Sang Min; Jang, Yong Ju

2013-01-01

Many valuable classification schemes for saddle nose have been suggested that integrate clinical deformity and treatment; however, there is no consensus regarding the most suitable classification and surgical method for saddle nose correction. To present clinical characteristics and treatment outcome of saddle nose deformity and to propose a modified classification system to better characterize the variety of different saddle nose deformities. The retrospective study included 91 patients who underwent rhinoplasty for correction of saddle nose from April 1, 2003, through December 31, 2011, with a minimum follow-up of 8 months. Saddle nose was classified into 4 types according to a modified classification. Aesthetic outcomes were classified as excellent, good, fair, or poor. Patients underwent minor cosmetic concealment by dorsal augmentation (n = 8) or major septal reconstruction combined with dorsal augmentation (n = 83). Autologous costal cartilages were used in 40 patients (44%), and homologous costal cartilages were used in 5 patients (6%). According to postoperative assessment, 29 patients had excellent, 42 patients had good, 18 patients had fair, and 2 patients had poor aesthetic outcomes. No statistical difference in surgical outcome according to saddle nose classification was observed. Eight patients underwent revision rhinoplasty, owing to recurrence of saddle, wound infection, or warping of the costal cartilage for dorsal augmentation. We introduce a modified saddle nose classification scheme that is simpler and better able to characterize different deformities. Among 91 patients with saddle nose, 20 (22%) had unsuccessful outcomes (fair or poor) and 8 (9%) underwent subsequent revision rhinoplasty. Thus, management of saddle nose deformities remains challenging. 4.

The Indian nose: An anthropometric analysis.

PubMed

Mehta, Nikhil; Srivastava, Rakesh K

2017-10-01

Anthropometric measurements of the nose are of great importance in planning aesthetic nasal surgery. Abundant literature is available on anthropometric analysis of Caucasians and Orientals, without similar references on the Indian nose and its regional differences. Thus, we conducted a descriptive cross-sectional epidemiological study of 1000 volunteers, with equal number of subjects derived from five geographic groups, namely North, Central, West, South, and the Himalayan region, to determine differences in nasal morphology of Indian population and among its various regions. The objective was to establish a standard Indian data for guidance in nasal surgery. All measurements were deduced using photographic analysis. The mean nasal height and width of our study population was 50.48 and 36.59 mm, respectively. Nasal profile varied among all five regions of the country. North Indians had the longest (52.69 mm nasal height) but the narrowest nose (35.01 mm width), thus having a leptorrhine nose with Caucasoid features. South Indians had the broadest nose (nasal width = 38.66 mm), whereas subjects from the Himalayan region had the shortest nose (nasal height = 47.2 mm). Indians on average had a mesorrhine nose as compared to Caucasians and Orientals who have a leptorrhine nose and Africans who have a platyrrhine nose. We thus conclude that the Indian nose should be considered a different entity in comparison to the nose of Caucasian, Oriental, and African populations. There are obvious differences in the facial architecture of people from different regions within the country. Therefore, appropriate adjustments need to be made according to different racial descents during nasal surgeries so as to give patients results that blend harmoniously with other facial features. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Tangent-ogive nose cones

NASA Technical Reports Server (NTRS)

Wing, L. D.

1976-01-01

Program calculates aerodynamic heating and shear stresses at wall for tangent-ogive noses that are slender enough to maintain an attached nose shock during portion of flight when heat transfer from boundary layer to wall is significant.

Different Ways to Apply a Measurement Instrument of E-Nose Type to Evaluate Ambient Air Quality with Respect to Odour Nuisance in a Vicinity of Municipal Processing Plants

PubMed Central

Szulczyński, Bartosz; Wasilewski, Tomasz; Wojnowski, Wojciech; Majchrzak, Tomasz; Dymerski, Tomasz; Namieśnik, Jacek; Gębicki, Jacek

2017-01-01

This review paper presents different ways to apply a measurement instrument of e-nose type to evaluate ambient air with respect to detection of the odorants characterized by unpleasant odour in a vicinity of municipal processing plants. An emphasis was put on the following applications of the electronic nose instruments: monitoring networks, remote controlled robots and drones as well as portable devices. Moreover, this paper presents commercially available sensors utilized in the electronic noses and characterized by the limit of quantification below 1 ppm v/v, which is close to the odour threshold of some odorants. Additionally, information about bioelectronic noses being a possible alternative to electronic noses and their principle of operation and application potential in the field of air evaluation with respect to detection of the odorants characterized by unpleasant odour was provided. PMID:29156597

Caudal Septal Stabilization Suturing Technique to Treat Crooked Noses.

PubMed

Baykal, Bahadir; Erdim, Ibrahim; Guvey, Ali; Oghan, Fatih; Kayhan, Fatma Tulin

2016-10-01

To rotate the nasal axis and septum to the midline using an L-strut graft and a novel caudal septal stabilization suturing technique to treat crooked noses. Thirty-six patients were included in the study. First, an L-strut graft was prepared by excising the deviated cartilage site in all patients. Second, multiple stabilization suturing, which we describe as a caudal septal stabilization suturing technique with a "fishing net"-like appearance, was applied between the anterior nasal spine and caudal septum in all patients. This new surgical technique, used to rotate the caudal septum, was applied to 22 I-type and 14 C-type crooked noses. Correction rates for the crooked noses were compared between the 2 inclination types with angular estimations. Deviation angles were measured using the AutoCAD 2012 software package and frontal (anterior) views, with the Frankfurt horizontal line parallel to the ground. Nasal axis angles showing angle improvement graded 4 categories as excellent, good, acceptable, and unsuccessful for evaluations at 6 months after surgery in the study. The success rate in the C-type nasal inclination was 86.7% (±21.9) and 88% (±16.7) in the I-type. The overall success rate of L-strut grafting and caudal septal stabilization suturing in crooked nose surgeries was 87.5% (±18.6). "Unsuccessful" results were not reported in any of the patients. L-strut grafting and caudal septal stabilization suturing techniques are efficacious in crooked noses according to objective measurement analysis results. However, a longer follow-up duration in a larger patient population is needed.

Nose Injuries and Disorders

MedlinePlus

... suffer. For example, the stuffy nose of the common cold can make it hard for you to breathe, sleep, or get comfortable. Many problems besides the common cold can affect the nose. They include Deviated septum - ...

Optical, colloidal and biological properties of up-converting nanoparticles embedded in polyester nanocarriers

NASA Astrophysics Data System (ADS)

Wawrzyńczyk, Dominika; Kulbacka, Julita; Bazylińska, Urszula

2017-08-01

We have investigated the change in optical properties and biocompatibility of up-converting NaYF4 nanoparticles (NPs) upon encapsulation inside the polyester nanocarriers (NCs) stabilized by Crempophor RH40 (CRH40), poly(D,L-lactide) (PLA), Pluronic P123 (P123). NaYF4:Er3+,Yb3+ NPs showed intense green and red emission, and upon encapsulation the increase of red band in respect to green one was observed, with no luminescence lifetime shortening. Obtained NCs showed prolonged colloidal stability and protective effect of the polymer shell simultaneously preserving the high emission efficiency of nanoparticles embedded within the silicon oil (SO) core. Based on emission spectra, kinetic measurements and cytotoxicity studies upon human malignant melanoma Me45 cell line we have shown the advantages of using polyester NCs as containers for the up-converting NPs. Due to the possibility of co-encapsulation of photosensitizers the obtained nanocarriers showed potential for application in theranostics.

Cationic nanocarriers induce cell necrosis through impairment of Na+/K+-ATPase and cause subsequent inflammatory response

PubMed Central

Wei, Xiawei; Shao, Bin; He, Zhiyao; Ye, Tinghong; Luo, Min; Sang, Yaxiong; Liang, Xiao; Wang, Wei; Luo, Shuntao; Yang, Shengyong; Zhang, Shuang; Gong, Changyang; Gou, Maling; Deng, Hongxing; Zhao, Yinglan; Yang, Hanshuo; Deng, Senyi; Zhao, Chengjian; Yang, Li; Qian, Zhiyong; Li, Jiong; Sun, Xun; Han, Jiahuai; Jiang, Chengyu; Wu, Min; Zhang, Zhirong

2015-01-01

Nanocarriers with positive surface charges are known for their toxicity which has limited their clinical applications. The mechanism underlying their toxicity, such as the induction of inflammatory response, remains largely unknown. In the present study we found that injection of cationic nanocarriers, including cationic liposomes, PEI, and chitosan, led to the rapid appearance of necrotic cells. Cell necrosis induced by cationic nanocarriers is dependent on their positive surface charges, but does not require RIP1 and Mlkl. Instead, intracellular Na+ overload was found to accompany the cell death. Depletion of Na+ in culture medium or pretreatment of cells with the Na+/K+-ATPase cation-binding site inhibitor ouabain, protected cells from cell necrosis. Moreover, treatment with cationic nanocarriers inhibited Na+/K+-ATPase activity both in vitro and in vivo. The computational simulation showed that cationic carriers could interact with cation-binding site of Na+/K+-ATPase. Mice pretreated with a small dose of ouabain showed improved survival after injection of a lethal dose of cationic nanocarriers. Further analyses suggest that cell necrosis induced by cationic nanocarriers and the resulting leakage of mitochondrial DNA could trigger severe inflammation in vivo, which is mediated by a pathway involving TLR9 and MyD88 signaling. Taken together, our results reveal a novel mechanism whereby cationic nanocarriers induce acute cell necrosis through the interaction with Na+/K+-ATPase, with the subsequent exposure of mitochondrial damage-associated molecular patterns as a key event that mediates the inflammatory responses. Our study has important implications for evaluating the biocompatibility of nanocarriers and designing better and safer ones for drug delivery. PMID:25613571

Preparation and Investigation of Amphiphilic Block Copolymers/Fullerene Nanocomposites as Nanocarriers for Hydrophobic Drug.

PubMed

Tan, Qinggang; Chu, Yanyan; Bie, Min; Wang, Zihao; Xu, Xiaoyan

2017-02-16

Biopolymer/inorganic material nanocomposites have attracted increasing interest as nanocarriers for delivering drugs owing to the combined advantages of both biopolymer and inorganic materials. Here, amphiphilic block copolymer/fullerene nanocomposites were prepared as nanocarriers for hydrophobic drug by incorporation of C60 in the core of methoxy polyethylene glycol-poly(d,l-lactic acid) (MPEG-PDLLA) micelles. The structure and morphology of MPEG-PDLLA/C60 nanocomposites were characterized using transmission electron microscopy, dynamic light scattering, high-resolution transmission electron microscopy, and thermal gravimetric analysis. It was found that the moderate amount of spherical C60 incorporated in the MPEG-PDLLA micelles may cause an increase in the molecular chain space of PDLLA segments in the vicinity of C60 and, thus, produce a larger cargo space to increase drug entrapment and accelerate the drug release from nanocomposites. Furthermore, sufficient additions of C60 perhaps resulted in an aggregation of C60 within the micelles that decreased the drug entrapment and produced a steric hindrance for DOX released from the nanocomposites. The results obtained provide fundamental insights into the understanding of the role of C60 in adjusting the drug loading and release of amphiphilic copolymer micelles and further demonstrate the future potential of the MPEG-PDLLA/C60 nanocomposites used as nanocarriers for controlled drug-delivery applications.

Genetically engineered nanocarriers for drug delivery.

PubMed

Shi, Pu; Gustafson, Joshua A; MacKay, J Andrew

2014-01-01

Cytotoxicity, low water solubility, rapid clearance from circulation, and off-target side-effects are common drawbacks of conventional small-molecule drugs. To overcome these shortcomings, many multifunctional nanocarriers have been proposed to enhance drug delivery. In concept, multifunctional nanoparticles might carry multiple agents, control release rate, biodegrade, and utilize target-mediated drug delivery; however, the design of these particles presents many challenges at the stage of pharmaceutical development. An emerging solution to improve control over these particles is to turn to genetic engineering. Genetically engineered nanocarriers are precisely controlled in size and structure and can provide specific control over sites for chemical attachment of drugs. Genetically engineered drug carriers that assemble nanostructures including nanoparticles and nanofibers can be polymeric or non-polymeric. This review summarizes the recent development of applications in drug and gene delivery utilizing nanostructures of polymeric genetically engineered drug carriers such as elastin-like polypeptides, silk-like polypeptides, and silk-elastin-like protein polymers, and non-polymeric genetically engineered drug carriers such as vault proteins and viral proteins.

Genetically engineered nanocarriers for drug delivery

PubMed Central

Shi, Pu; Gustafson, Joshua A; MacKay, J Andrew

2014-01-01

Cytotoxicity, low water solubility, rapid clearance from circulation, and off-target side-effects are common drawbacks of conventional small-molecule drugs. To overcome these shortcomings, many multifunctional nanocarriers have been proposed to enhance drug delivery. In concept, multifunctional nanoparticles might carry multiple agents, control release rate, biodegrade, and utilize target-mediated drug delivery; however, the design of these particles presents many challenges at the stage of pharmaceutical development. An emerging solution to improve control over these particles is to turn to genetic engineering. Genetically engineered nanocarriers are precisely controlled in size and structure and can provide specific control over sites for chemical attachment of drugs. Genetically engineered drug carriers that assemble nanostructures including nanoparticles and nanofibers can be polymeric or non-polymeric. This review summarizes the recent development of applications in drug and gene delivery utilizing nanostructures of polymeric genetically engineered drug carriers such as elastin-like polypeptides, silk-like polypeptides, and silk-elastin-like protein polymers, and non-polymeric genetically engineered drug carriers such as vault proteins and viral proteins. PMID:24741309

The Twisted Nose: What to Do When It's Not Straight.

PubMed

Gonzalez, Joseph R; Winkler, Andrew A

2018-06-01

Septorhinoplasty is among the most common facial plastic and reconstructive surgeries and its complexities are reflected in a relatively high revision rate. The patient with a postoperative twisted nose presents an additional challenge and requires that the surgeon display empathy and possess a deep knowledge of the aesthetic and functional intricacies of the nose. Correction of the twisted nose should be approached in a systematic fashion with unique considerations for each "third" of the nose. While there are many options in the overall surgical armamentarium, each surgeon will find specific techniques that are most efficacious and reproducible for their individual practice. This article discusses select surgical "pearls" and techniques that can aid the surgeon in their own surgical decision-making. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Multifunctional Triblock Nanocarrier (PAMAM-PEG-PLL) for the Efficient Intracellular siRNA Delivery and Gene Silencing

PubMed Central

2011-01-01

A novel triblock poly(amido amine)-poly(ethylene glycol)-poly-l-lysine (PAMAM-PEG-PLL) nanocarrier was designed, synthesized, and evaluated for the delivery of siRNA. The design of the nanocarrier is unique and provides a solution to most of the common problems associated with the delivery and therapeutic applications of siRNA. Every component in the triblock nanocarrier plays a significant role and performs multiple functions: (1) tertiary amine groups in the PAMAM dendrimer work as a proton sponge and play a vital role in the endosomal escape and cytoplasmic delivery of siRNA; (2) PEG, a linker connecting PLL and PAMAM dendrimers renders nuclease stability and protects siRNA in human plasma; (3) PLL provides primary amines to form polyplexes with siRNA through electrostatic interaction and also acts as penetration enhancer; and (4) conjugation to PEG and PAMAM reduced toxicity of PLL and the entire triblock nanocarrier PAMAM-PEG-PLL. The data obtained show that the polyplexes resulted from the conjugation of siRNA, and the proposed nanocarriers were effectively taken up by cancer cells and induced the knock down of the target BCL2 gene. In addition, triblock nanocarrier/siRNA polyplexes showed excellent stability in human plasma. PMID:21322531

Nanocarrier-Integrated Microspheres: Nanogel Tectonic Engineering for Advanced Drug-Delivery Systems.

PubMed

Tahara, Yoshiro; Mukai, Sada-Atsu; Sawada, Shin-Ichi; Sasaki, Yoshihiro; Akiyoshi, Kazunari

2015-09-09

A nanocarrier-integrated bottom-up method is a promising strategy for advanced drug-release systems. Self-assembled nanogels, which are one of the most beneficial nanocarriers for drug-delivery systems, are tectonically integrated to prepare nanogel-crosslinked (NanoClik) microspheres. NanoClik microspheres consisting of nanogel-derived structures (observed by STED microscopy) release "drug-loaded nanogels" after hydrolysis, resulting in successful sustained drug delivery in vivo. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Reversibly crosslinked nanocarriers for on-demand drug delivery in cancer treatment

PubMed Central

Shao, Yu; Huang, Wenzhe; Shi, Changying; Atkinson, Sean T; Luo, Juntao

2013-01-01

Polymer micelles have proven to be one of the most versatile nanocarriers for anticancer drug delivery. However, the in vitro and in vivo stability of micelles remains a challenge due to the dynamic nature of these self-assembled systems, which leads to premature drug release and nonspecific biodistribution in vivo. Recently, reversibly crosslinked micelles have been developed to provide solutions to stabilize nanocarriers in blood circulation. Increased stability allows nanoparticles to accumulate at tumor sites efficiently via passive and/or active tumor targeting, while cleavage of the micelle crosslinkages, through internal or external stimuli, facilitates on-demand drug release. In this review, various crosslinking chemistries as well as the choices for reversible linkages in these nanocarriers will be introduced. Then, the development of reversibly crosslinked micelles for on-demand drug release in response to single or dual stimuli in the tumor microenvironment is discussed, for example, acidic pH, reducing microenvironment, enzymatic microenvironment, photoirradiation and the administration of competitive reagents postmicelle delivery. PMID:23323559

Electronic nose for space program applications

NASA Technical Reports Server (NTRS)

Young, Rebecca C.; Buttner, William J.; Linnell, Bruce R.; Ramesham, Rajeshuni

2003-01-01

The ability to monitor air contaminants in the shuttle and the International Space Station is important to ensure the health and safety of astronauts, and equipment integrity. Three specific space applications have been identified that would benefit from a chemical monitor: (a) organic contaminants in space cabin air; (b) hypergolic propellant contaminants in the shuttle airlock; (c) pre-combustion signature vapors from electrical fires. NASA at Kennedy Space Center (KSC) is assessing several commercial and developing electronic noses (E-noses) for these applications. A short series of tests identified those E-noses that exhibited sufficient sensitivity to the vapors of interest. Only two E-noses exhibited sufficient sensitivity for hypergolic fuels at the required levels, while several commercial E-noses showed sufficient sensitivity of common organic vapors. These E-noses were subjected to further tests to assess their ability to identify vapors. Development and testing of E-nose models using vendor supplied software packages correctly identified vapors with an accuracy of 70-90%. In-house software improvements increased the identification rates between 90 and 100%. Further software enhancements are under development. Details on the experimental setup, test protocols, and results on E-nose performance are presented in this paper along with special emphasis on specific software enhancements. c2003 Elsevier Science B.V. All rights reserved.

Intranasal agomelatine solid lipid nanoparticles to enhance brain delivery: formulation, optimization and in vivo pharmacokinetics

PubMed Central

Fatouh, Ahmed M; Elshafeey, Ahmed H; Abdelbary, Ahmed

2017-01-01

Purpose Agomelatine is a novel antidepressant drug suffering from an extensive first-pass metabolism leading to a diminished absolute bioavailability. The aim of the study is: first to enhance its absolute bioavailability, and second to increase its brain delivery. Methods To achieve these aims, the nasal route was adopted to exploit first its avoidance of the hepatic first-pass metabolism to increase the absolute bioavailability, and second the direct nose-to-brain pathway to enhance the brain drug delivery. Solid lipid nanoparticles were selected as a drug delivery system to enhance agomelatine permeability across the blood–brain barrier and therefore its brain delivery. Results The optimum solid lipid nanoparticles have a particle size of 167.70 nm ±0.42, zeta potential of −17.90 mV ±2.70, polydispersity index of 0.12±0.10, entrapment efficiency % of 91.25%±1.70%, the percentage released after 1 h of 35.40%±1.13% and the percentage released after 8 h of 80.87%±5.16%. The pharmacokinetic study of the optimized solid lipid nanoparticles revealed a significant increase in each of the plasma peak concentration, the AUC(0–360 min) and the absolute bioavailability compared to that of the oral suspension of Valdoxan® with the values of 759.00 ng/mL, 7,805.69 ng⋅min/mL and 44.44%, respectively. The optimized solid lipid nanoparticles gave a drug-targeting efficiency of 190.02, which revealed more successful brain targeting by the intranasal route compared with the intravenous route. The optimized solid lipid nanoparticles had a direct transport percentage of 47.37, which indicates a significant contribution of the direct nose-to-brain pathway in the brain drug delivery. Conclusion The intranasal administration of agomelatine solid lipid nanoparticles has effectively enhanced both the absolute bioavailability and the brain delivery of agomelatine. PMID:28684900

New doxorubicin nanocarriers based on cyclodextrins.

PubMed

Viale, Maurizio; Giglio, Valentina; Monticone, Massimiliano; Maric, Irena; Lentini, Giovanni; Rocco, Mattia; Vecchio, Graziella

2017-10-01

Polymeric nanoparticles and fibrin gels (FBGs) are attractive biomaterials for local delivery of a variety of biotherapeutic agents, from drugs to proteins. We combined these different drug delivery approaches by preparing nanoparticle-loaded FBGs characterized by their intrinsic features of drug delivery rate and antiproliferative/apoptotic activities. Inclusion complexes of doxorubicin (DOXO) with oligomeric β-cyclodextrins (oCyD) functionalized with different functional groups were studied. These nanocarriers were able to interact with FBGs as shown by a decreased release rate of DOXO. One of these complexes, oCyDNH 2 /DOXO, demonstrated good antiproliferative and apoptotic activity in vitro, reflecting a higher drug uptake by cells. As hypothesized, the nanocarrier/FBG complexes showed a lower drug release rate than similar FBGs loaded with the corresponding non-functionalized oCyD/DOXO. Taken together, our results provide experimental evidence that oCyDNH 2 /DOXO complexes may be useful components in enhanced FBGs and further build support for the great promise these complex molecules hold for clinical use in localized anticancer therapy of inoperable or surgically removable tumors of different histological origin.

Ocular Drug Delivery Barriers-Role of Nanocarriers in the Treatment of Anterior Segment Ocular Diseases.

PubMed

Bachu, Rinda Devi; Chowdhury, Pallabitha; Al-Saedi, Zahraa H F; Karla, Pradeep K; Boddu, Sai H S

2018-02-27

Ocular drug delivery is challenging due to the presence of anatomical and physiological barriers. These barriers can affect drug entry into the eye following multiple routes of administration (e.g., topical, systemic, and injectable). Topical administration in the form of eye drops is preferred for treating anterior segment diseases, as it is convenient and provides local delivery of drugs. Major concerns with topical delivery include poor drug absorption and low bioavailability. To improve the bioavailability of topically administered drugs, novel drug delivery systems are being investigated. Nanocarrier delivery systems demonstrate enhanced drug permeation and prolonged drug release. This review provides an overview of ocular barriers to anterior segment delivery, along with ways to overcome these barriers using nanocarrier systems. The disposition of nanocarriers following topical administration, their safety, toxicity and clinical trials involving nanocarrier systems are also discussed.

Ocular Drug Delivery Barriers—Role of Nanocarriers in the Treatment of Anterior Segment Ocular Diseases

PubMed Central

Bachu, Rinda Devi; Chowdhury, Pallabitha; Al-Saedi, Zahraa H. F.; Karla, Pradeep K.; Boddu, Sai H. S.

2018-01-01

Ocular drug delivery is challenging due to the presence of anatomical and physiological barriers. These barriers can affect drug entry into the eye following multiple routes of administration (e.g., topical, systemic, and injectable). Topical administration in the form of eye drops is preferred for treating anterior segment diseases, as it is convenient and provides local delivery of drugs. Major concerns with topical delivery include poor drug absorption and low bioavailability. To improve the bioavailability of topically administered drugs, novel drug delivery systems are being investigated. Nanocarrier delivery systems demonstrate enhanced drug permeation and prolonged drug release. This review provides an overview of ocular barriers to anterior segment delivery, along with ways to overcome these barriers using nanocarrier systems. The disposition of nanocarriers following topical administration, their safety, toxicity and clinical trials involving nanocarrier systems are also discussed. PMID:29495528

Nose Hill Artifacts

ERIC Educational Resources Information Center

Hansen, Vivian

2008-01-01

A Blackfoot woman, caught in the act of adultery, was condemned at this site to have her nose cut off as a penalty for her actions. People do not know her story. The tribe cast it on the ground. And so She, Nose Hill, was named. John Laurie Boulevard holds her mound in a circlet of asphalt, defining the map of her "terra incognita." She…

Nose: Applied Aspects in Dermatology

PubMed Central

Lakshmi, Dammaningala Venkataramaiah; Shilpa, Kanathur; Nataraja, Holavanahally Veerabhadrappa; Divya, Kallapa Gorur

2016-01-01

Nose is the most prominent part of the mid-face and has important physiological, aesthetic and psychological functions. Skin diseases on the nose are commonly seen by dermatologists, otorhinolaryngologists, and plastic surgeons. Because of its exposed, highly visible localization, lesions on the skin of the nose are often noticed by patients themselves, typically very early in the course of the disease. Similarly, the dermatological lexicon is well known with descriptive terminologies, synonyms, acronyms, eponyms, toponyms, misnomers. We have tried to compile the anatomical applications of nose in cosmetology and dermatosurgery subspecialities with nasal eponyms and signs encountered in clinical dermatology that would be helpful for residents. PMID:27057038

Nose: Applied Aspects in Dermatology.

PubMed

Lakshmi, Dammaningala Venkataramaiah; Shilpa, Kanathur; Nataraja, Holavanahally Veerabhadrappa; Divya, Kallapa Gorur

2016-01-01

Nose is the most prominent part of the mid-face and has important physiological, aesthetic and psychological functions. Skin diseases on the nose are commonly seen by dermatologists, otorhinolaryngologists, and plastic surgeons. Because of its exposed, highly visible localization, lesions on the skin of the nose are often noticed by patients themselves, typically very early in the course of the disease. Similarly, the dermatological lexicon is well known with descriptive terminologies, synonyms, acronyms, eponyms, toponyms, misnomers. We have tried to compile the anatomical applications of nose in cosmetology and dermatosurgery subspecialities with nasal eponyms and signs encountered in clinical dermatology that would be helpful for residents.

Novel bio-active lipid nanocarriers for the stabilization and sustained release of sitosterol

NASA Astrophysics Data System (ADS)

Lacatusu, I.; Badea, N.; Stan, R.; Meghea, A.

2012-11-01

In this work, new stable and efficiently bio-active lipid nanocarriers (NLCs) with antioxidant properties have been developed for the transport of active ingredients in food. The novel NLCs loaded with β-sitosterol/β-sitosterol and green tea extract (GTE) and prepared by a combination of natural oils (grape seed oil, fish oil and squalene) and biological lipids with food grade surfactants, were physico-chemically examined by DLS, TEM, electrokinetic potential, DSC and HPLC and found to have main diameters less than 200 nm, a spherical morphology, excellent physical stability, an imperfect crystalline lattice and high entrapment efficiency. The novel loaded-NLCs have demonstrated the potential to develop a high blocking action of chain reactions, trapping up to 92% of the free-oxygen radicals, as compared to the native β-sitosterol (AA%=36.5). Another advantage of this study is associated with the quality of bio-active NLCs based on grape seed oil and squalene to manifest a better sitosterol—sustained release behaviour as compared to their related nanoemulsions. By coupling both in vitro results, i.e. the enhanced antioxidant activity and superior release properties, this study emphasizes the sustainability of novel bio-active nanocarriers to gain specific bio-food features for development of functional foods with a high applicability spectrum.

Strain Behavior of Concrete Panels Subjected to Different Nose Shapes of Projectile Impact

PubMed Central

Lee, Sangkyu; Kim, Gyuyong; Kim, Hongseop; Son, Minjae; Choe, Gyeongcheol; Nam, Jeongsoo

2018-01-01

This study evaluates the fracture properties and rear-face strain distribution of nonreinforced and hooked steel fiber-reinforced concrete panels penetrated by projectiles of three different nose shapes: sharp, hemispherical, and flat. The sharp projectile nose resulted in a deeper penetration because of the concentration of the impact force. Conversely, the flat projectile nose resulted in shallower penetrations. The penetration based on different projectile nose shapes is directly related to the impact force transmitted to the rear face. Scabbing can be more accurately predicted by the tensile strain on the rear face of concrete due to the projectile nose shape. The tensile strain on the rear face of the concrete was reduced by the hooked steel fiber reinforcement because the hooked steel fiber absorbed some of the impact stress transmitted to the rear face of the concrete. Consequently, the strain behavior on the rear face of concrete according to the projectile nose shape was confirmed. PMID:29522479

Strain Behavior of Concrete Panels Subjected to Different Nose Shapes of Projectile Impact.

PubMed

Lee, Sangkyu; Kim, Gyuyong; Kim, Hongseop; Son, Minjae; Choe, Gyeongcheol; Nam, Jeongsoo

2018-03-09

This study evaluates the fracture properties and rear-face strain distribution of nonreinforced and hooked steel fiber-reinforced concrete panels penetrated by projectiles of three different nose shapes: sharp, hemispherical, and flat. The sharp projectile nose resulted in a deeper penetration because of the concentration of the impact force. Conversely, the flat projectile nose resulted in shallower penetrations. The penetration based on different projectile nose shapes is directly related to the impact force transmitted to the rear face. Scabbing can be more accurately predicted by the tensile strain on the rear face of concrete due to the projectile nose shape. The tensile strain on the rear face of the concrete was reduced by the hooked steel fiber reinforcement because the hooked steel fiber absorbed some of the impact stress transmitted to the rear face of the concrete. Consequently, the strain behavior on the rear face of concrete according to the projectile nose shape was confirmed.

Lipid based nanocarriers system for topical delivery of photosensitizers.

PubMed

Md, Shadab; Haque, Shadabul; Madheswaran, Thiagarajan; Zeeshan, Farrukh; Meka, Venkata Srikanth; Radhakrishnan, Ammu K; Kesharwani, Prashant

2017-08-01

Topical photodynamic therapy (PDT) is a non-invasive technique used in the treatment of malignant and non-malignant skin diseases. It offers great promise because of its simplicity, enhanced patient compliance, localisation of the photosensitizer, as well as the use of light and oxygen to achieve photocytotoxicity. Despite progress in photosensitizer-mediated topical PDT, its clinical application is limited by poor penetration of photosensitizers through the skin. Therefore, much effort has been made to develop nanocarriers that can tackle the challenges of conventional photosensitizer-mediated PDT for topical delivery. This review discusses recent data on the use of different types of lipid-based nanocarriers in delivering photosensitizer for topical PDT. Copyright © 2017 Elsevier Ltd. All rights reserved.

Locoregional Confinement and Major Clinical Benefit of 188Re-Loaded CXCR4-Targeted Nanocarriers in an Orthotopic Human to Mouse Model of Glioblastoma.

PubMed

Séhédic, Delphine; Chourpa, Igor; Tétaud, Clément; Griveau, Audrey; Loussouarn, Claire; Avril, Sylvie; Legendre, Claire; Lepareur, Nicolas; Wion, Didier; Hindré, François; Davodeau, François; Garcion, Emmanuel

2017-01-01

Gold standard beam radiation for glioblastoma (GBM) treatment is challenged by resistance phenomena occurring in cellular populations well prepared to survive or to repair damage caused by radiation. Among signals that have been linked with radio-resistance, the SDF1/CXCR4 axis, associated with cancer stem-like cell, may be an opportune target. To avoid the problem of systemic toxicity and blood-brain barrier crossing, the relevance and efficacy of an original system of local brain internal radiation therapy combining a radiopharmaceutical with an immuno-nanoparticle was investigated. The nanocarrier combined lipophilic thiobenzoate complexes of rhenium-188 loaded in the core of a lipid nanocapsule (LNC 188 Re) with a function-blocking antibody, 12G5 directed at the CXCR4, on its surface. The efficiency of 12G5-LNC 188 Re was investigated in an orthotopic and xenogenic GBM model of CXCR4-positive U87MG cells implanted in the striatum of Scid mice. We demonstrated that 12G5-LNC 188 Re single infusion treatment by convection-enhanced delivery resulted in a major clinical improvement in median survival that was accompanied by locoregional effects on tumor development including hypovascularization and stimulation of the recruitment of bone marrow derived CD11b- or CD68-positive cells as confirmed by immunohistochemistry analysis. Interestingly, thorough analysis by spectral imaging in a chimeric U87MG GBM model containing CXCR4-positive/red fluorescent protein (RFP)-positive- and CXCR4-negative/RFP-negative-GBM cells revealed greater confinement of DiD-labeled 12G5-LNCs than control IgG2a-LNCs in RFP compartments. Main conclusion: These findings on locoregional impact and targeting of disseminated cancer cells in tumor margins suggest that intracerebral active targeting of nanocarriers loaded with radiopharmaceuticals may have considerable benefits in clinical applications.

Locoregional Confinement and Major Clinical Benefit of 188Re-Loaded CXCR4-Targeted Nanocarriers in an Orthotopic Human to Mouse Model of Glioblastoma

PubMed Central

Séhédic, Delphine; Chourpa, Igor; Tétaud, Clément; Griveau, Audrey; Loussouarn, Claire; Avril, Sylvie; Legendre, Claire; Lepareur, Nicolas; Wion, Didier; Hindré, François; Davodeau, François; Garcion, Emmanuel

2017-01-01

Purpose: Gold standard beam radiation for glioblastoma (GBM) treatment is challenged by resistance phenomena occurring in cellular populations well prepared to survive or to repair damage caused by radiation. Among signals that have been linked with radio-resistance, the SDF1/CXCR4 axis, associated with cancer stem-like cell, may be an opportune target. To avoid the problem of systemic toxicity and blood-brain barrier crossing, the relevance and efficacy of an original system of local brain internal radiation therapy combining a radiopharmaceutical with an immuno-nanoparticle was investigated. Experiment design: The nanocarrier combined lipophilic thiobenzoate complexes of rhenium-188 loaded in the core of a lipid nanocapsule (LNC188Re) with a function-blocking antibody, 12G5 directed at the CXCR4, on its surface. The efficiency of 12G5-LNC188Re was investigated in an orthotopic and xenogenic GBM model of CXCR4-positive U87MG cells implanted in the striatum of Scid mice. Results: We demonstrated that 12G5-LNC188Re single infusion treatment by convection-enhanced delivery resulted in a major clinical improvement in median survival that was accompanied by locoregional effects on tumor development including hypovascularization and stimulation of the recruitment of bone marrow derived CD11b- or CD68-positive cells as confirmed by immunohistochemistry analysis. Interestingly, thorough analysis by spectral imaging in a chimeric U87MG GBM model containing CXCR4-positive/red fluorescent protein (RFP)-positive- and CXCR4-negative/RFP-negative-GBM cells revealed greater confinement of DiD-labeled 12G5-LNCs than control IgG2a-LNCs in RFP compartments. Main conclusion: These findings on locoregional impact and targeting of disseminated cancer cells in tumor margins suggest that intracerebral active targeting of nanocarriers loaded with radiopharmaceuticals may have considerable benefits in clinical applications. PMID:29158842

The Gendered Nose and its Lack: "Medieval" Nose-Cutting and its Modern Manifestations.

PubMed

Skinner, Patricia

2014-01-01

Time magazine's cover photograph in August 2010 of a noseless Afghan woman beside the emotive strap line, "What happens if we leave Afghanistan," fuelled debate about the "medieval" practices of the Taliban, whose local commander had instructed her husband to take her nose and ears. Press reports attributed the violence to the Pashtun tradition that a dishonored husband "lost his nose." This equation of nose-cutting with tradition begs questions not only about the Orientalist lens of the western press when viewing Afghanistan, but also about the assumption that the word "medieval" can function as a label for such practices. A study of medieval nose-cutting suggests that its identification as an "eastern" practice should be challenged. Rather clearer is its connection with patriarchal values of authority and honor: the victims of such punishment have not always been women, but this is nevertheless a gendered punishment of the powerless by the powerful.

Formulation and delivery of itraconazole to the brain using a nanolipid carrier system

PubMed Central

Lim, Wei Meng; Rajinikanth, Paruvathanahalli Siddalingam; Mallikarjun, Chitneni; Kang, Yew Beng

2014-01-01

The objectives of this study were to develop and characterize itraconazole (ITZ)-loaded nanostructured lipid carriers (NLCs) and to study their potential for drug delivery into the brain. Precirol® ATO 5 and Transcutol® HP were selected as the lipid phase, and Tween® 80 and Solutol® HS15 as surfactants. The ITZ-NLCs were prepared by a hot and high-pressure homogenization method. The entrapment efficiency for the best formulation batch was analyzed using high-performance liquid chromatography and was found to be 70.5%±0.6%. The average size, zeta potential, and polydispersity index for the ITZ-NLCs used for animal studies were found to be 313.7±15.3 nm, −18.7±0.30 mV, and 0.562±0.070, respectively. Transmission electron microscopy confirmed that ITZ-NLCs were spherical in shape, with a size of less than 200 nm. Differential scanning calorimetry and X-ray diffractometry analysis showed that ITZ was encapsulated in the lipid matrix and present in the amorphous form. The in vitro release study showed that ITZ-NLCs achieved a sustained release, with cumulative release of 80.6%±5.3% up to 24 hours. An in vivo study showed that ITZ-NLCs could increase the ITZ concentration in the brain by almost twofold. These results suggest that ITZ-NLCs can be exploited as nanocarriers to achieve sustained release and brain-targeted delivery. PMID:24833900

Fully glutathione degradable waterborne polyurethane nanocarriers: Preparation, redox-sensitivity, and triggered intracellular drug release.

PubMed

Omrani, Ismail; Babanejad, Niloofar; Shendi, Hasan Kashef; Nabid, Mohammad Reza

2017-01-01

Polyurethanes are important class of biomaterials that are extensively used in medical devices. In spite of their easy synthesis, polyurethanes that are fully degradable in response to the intracellular reducing environment are less explored for controlled drug delivery. Herein, a novel glutathione degradable waterborne polyurethane (WPU) nanocarrier for redox triggered intracellular delivery of a model lipophilic anticancer drug, doxorubicin (DOX) is reported. The WPU was prepared from polyaddition reaction of isophorone diisocyanate (IPDI) and a novel linear polyester polyol involving disulfide linkage, disulfide labeled chain extender, dimethylolpropionic acid (DMPA) using dibutyltin dilaurate (DBTDL) as a catalyst. The resulting polyurethane self-assembles into nanocarrier in water. The dynamic light scattering (DLS) measurements and scanning electron microscope (SEM) revealed fast swelling and disruption of nanocarriers under an intracellular reduction-mimicking environment. The in vitro release studies showed that DOX was released in a controlled and redox-dependent manner. MTT assays showed that DOX-loaded WPU had a high in vitro antitumor activity in both HDF noncancer cells and MCF- 7 cancer cells. In addition, it is found that the blank WPU nanocarriers are nontoxic to HDF and MCF-7 cells even at a high concentration of 2mg/mL. Hence, nanocarriers based on disulfide labeled WPU have appeared as a new class of biocompatible and redox-degradable nanovehicle for efficient intracellular drug delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

pH-sensitive nanocarrier based on gold/silver core-shell nanoparticles decorated multi-walled carbon manotubes for tracing drug release in living cells.

PubMed

Chen, Peng; Wang, Zhuyuan; Zong, Shenfei; Zhu, Dan; Chen, Hui; Zhang, Yizhi; Wu, Lei; Cui, Yiping

2016-01-15

We fabricate a multifunctional nanocarrier based on multi-walled carbon nanotubes (MWCNTs) decorated with gold/silver core-shell nanoparticles (Au@Ag NPs) and fluorescein isothiocyanate (FITC) for tracking the intracellular drug release process. In the demonstrated nanocarrier, the Au@Ag NPs adsorbed on the surface of MWCNTs were labeled with the pH-dependent SERS reporter 4-Mercaptobenzoic acid (4MBA) for SERS based pH sensing. FITC was conjugated on MWCNTs to provide fluorescence signal for tracing the MWCNTs. Fluorescent doxorubicin (DOX) was used as the model drug which can be loaded onto MWCNTs via π-π stacking and released from the MWCNTs under acidic condition. By detecting the SERS spectrum of 4MBA, the pH value around the nanocarrier could be monitored. Besides, by tracing the fluorescence of FITC and DOX, we can also investigate the drug release process in cells. Experimental results show that the proposed nanocarrier retained a well pH-sensitive performance in living cells, and the DOX detached from MWCNTs inside the lysosomes and entered into the cytoplasm with the MWCNTs being left in lysosomes. To further investigate the drug release dynamics, 2-D color-gradient pH mapping were plotted, which were calculated from the SERS spectra of 4MBA. The detailed release process and carrier distribution have been recorded as environmental pH changes during cell endocytosis. Furthermore, we also confirmed that the proposed nanocarrier has a good biocompatibility. It indicates that the designed nanocarrier have a great potential in intraceable drug delivery, cancer cells imaging and pH monitoring. Copyright © 2015 Elsevier B.V. All rights reserved.

Photochemical mechanisms of light-triggered release from nanocarriers

PubMed Central

Fomina, Nadezda; Sankaranarayanan, Jagadis; Almutairi, Adah

2012-01-01

Over the last three decades, a handful of photochemical mechanisms have been applied to a large number of nanoscale assemblies that encapsulate a payload to afford spatio-temporal and remote control over activity of the encapsulated payload. Many of these systems are designed with an eye towards biomedical applications, as spatio-temporal and remote control of bioactivity would advance research and clinical practice. This review covers five underlying photochemical mechanisms that govern the activity of the majority of photoresponsive nanocarriers: 1. photo driven isomerization and oxidation, 2. surface plasmon absorption and photothermal effects, 3. photo driven hydrophobicity changes, 4. photo driven polymer backbone fragmentation and 5. photo driven de-crosslinking. The ways in which these mechanisms have been incorporated into nanocarriers and how they affect release is detailed, as well as the advantages and disadvantages of each system. PMID:22386560

Fat grafting to the nose: personal experience with 36 patients.

PubMed

Monreal, Juan

2011-10-01

Clinicians are facing an increasing trend toward nonsurgical nose reshaping using synthetic injectables, mainly for patients who refuse standard rhinoplasties. Autologous fat grafting is a safer and convenient alternative to permanent or semipermanent injectables due to better results as well as fewer and milder side effects. The author reports his experience with fat grafting to the nose using his personal technique for 36 consecutive patients. The experience covers primary treatments of noses not treated by surgery, treatment of post rhinoplasty deformities, and combination fat grafting and rhinoplasties. The technique used by the author for fat grafting to the nose does not differ significantly from that used for other body or face areas. It is based in the atraumatic extraction of fat fragments using a multi-orifice cannula and injection of these fragments using 1.4- to 1.6-mm cannulas or needles. In combining rhinoplasties with fat grafting, fat grafts are used in the same location instead of a prosthesis or cartilage grafts. The initial analysis of postoperative results showed a good to high level of patient satisfaction, particularly in primary cases, with virtually no complications or severe side effects. Some easily corrected side effects probably were learning curve dependent. Autologous fat grafting is an effective and reliable technique for aesthetic and reconstructive nose reshaping for patients who refuse surgical treatments. Although optimal results can be achieved with this technique, they are not comparable with those obtained by surgical rhinoplasties, and this is an important issue to discuss with the prospective patient.

Nanocarriers in ocular drug delivery: an update review.

PubMed

Wadhwa, Sheetu; Paliwal, Rishi; Paliwal, Shivani Rai; Vyas, S P

2009-01-01

Controlled drug delivery to eye is one of the most challenging fields of pharmaceutical research. Low drug-contact time and poor ocular bioavailability due to drainage of solution, tear turnover and its dilution or lacrimation are the problems associated with conventional systems. In addition, anatomical barriers and physiological conditions of eye are also important parameters which control designing of drug delivery systems. Nanosized carriers like micro/nano-suspensions, liposome, niosome, dendrimer, nanoparticles, ocular inserts, implants, hydrogels and prodrug approaches have been developed for this purpose. These novel systems offer manifold advantages over conventional systems as they increase the efficiency of drug delivery by improving the release profile and also reduce drug toxicity. Conventional delivery systems get diluted with tear, washed away through the lacrimal gland and usually require administering at regular time intervals whereas nanocarriers release drug at constant rate for a prolonged period of time and thus enhance its absorption and site specific delivery. This review presents an overview of the various aspects of the ocular drug delivery, with special emphasis on nanocarrier based strategies, including structure of eye, its barriers, delivery routes and the challenges/limitations associated with development of novel nanocarriers. The recent progresses in therapy of ocular disease like gene therapy have also been included so that future options should also be considered from the delivery point of view. Recent progress in the delivery of proteins and peptides via ocular route has also been incorporated for reader benefit.

Sniffing out cancer using the JPL electronic nose: a pilot study of a novel approach to detection and differentiation of brain cancer.

PubMed

Kateb, Babak; Ryan, M A; Homer, M L; Lara, L M; Yin, Yufang; Higa, Kerin; Chen, Mike Y

2009-08-01

A proof-of-concept study was done to determine whether an electronic nose developed for air quality monitoring at the Jet Propulsion Laboratory (JPL) could be used to distinguish between the odors of organ and tumor tissues, with an eye to using such a device as one of several modes in multi-modal imaging and tumor differentiation during surgery. We hypothesized that the JPL electronic nose (ENose) would be able to distinguish between the odors of various organ and tumor tissues. The odor signatures, or array response, of two organs, chicken heart and chicken liver, and cultured glioblastoma and melanoma tumor cell lines were recorded using the JPL Electronic Nose. The overall array responses were compared to determine whether they were sufficiently different to allow the organs and cell lines to be identified by their array responses. The ENose was able to distinguish between the two types of organ tissue and between the two types of tumor cell lines. The variation in array response for the organ tissues was 19% and between the two types of cultured cell lines was 22%. This study shows that it is possible to use an electronic nose to distinguish between two types of tumor cells and between two types of organ tissue. As we conducted the experiment with a sensor array built for air quality monitoring rather than for medical purposes, it may be possible to select an array that is optimized to distinguish between different types of cells and organ tissues. Further focused studies are needed to investigate the odor signatures of different cells as well as cellular proliferation, growth, differentiation and infiltration.

White-Light Supercontinuum Laser-Based Multiple Wavelength Excitation for TCSPC-FLIM of Cutaneous Nanocarrier Uptake

NASA Astrophysics Data System (ADS)

Volz, Pierre; Brodwolf, Robert; Zoschke, Christian; Haag, Rainer; Schäfer-Korting, Monika; Alexiev, Ulrike

2018-05-01

We report here on a custom-built time-correlated single photon-counting (TCSPC)-based fluorescence lifetime imaging microscopy (FLIM) setup with a continuously tunable white-light supercontinuum laser combined with acousto-optical tunable filters (AOTF) as an excitation source for simultaneous excitation of multiple spectrally separated fluorophores. We characterized the wavelength dependence of the white-light supercontinuum laser pulse properties and demonstrated the performance of the FLIM setup, aiming to show the experimental setup in depth together with a biomedical application. We herein summarize the physical-technical parameters as well as our approach to map the skin uptake of nanocarriers using FLIM with a resolution compared to spectroscopy. As an example, we focus on the penetration study of indocarbocyanine-labeled dendritic core-multishell nanocarriers (CMS-ICC) into reconstructed human epidermis. Unique fluorescence lifetime signatures of indocarbocyanine-labeled nanocarriers indicate nanocarrier-tissue interactions within reconstructed human epidermis, bringing FLIM close to spectroscopic analysis.

Self-assembled stable sponge-type nanocarries for Brucea javanica oil delivery.

PubMed

Zou, Aihua; Li, Yawen; Chen, Yiyin; Angelova, Angelina; Garamus, Vasil M; Li, Na; Drechsler, Markus; Angelov, Borislav; Gong, Yabin

2017-05-01

Sponge-type nanocarriers (spongosomes) are produced upon dispersion of a liquid crystalline sponge phase formed by self-assembly of an amphiphilic lipid in excess aqueous phase. The inner organization of the spongosomes is built-up by randomly ordered bicontinuous lipid membranes and their surfaces are stabilized by alginate chains providing stealth properties and colloidal stability. The present study elaborates spongosomes for improved encapsulation of Brucea javanica oil (BJO), a traditional Chinese medicine that may strongly inhibit proliferation and metastasis of various cancers. The inner structural organization and the morphology characteristics of BJO-loaded nanocarriers at varying quantities of BJO were determined by cryogenic transmission electron microscopy (Cryo-TEM), small angle X-ray scattering (SAXS) and dynamic light scattering (DLS). Additionally, the drug loading and drug release profiles for BJO-loaded spongosome systems also were determined. We found that the sponge-type liquid crystalline lipid membrane organization provides encapsulation efficiency rate of BJO as high as 90%. In vitro cytotoxicity and apoptosis study of BJO spongosome nanoparticles with A549 cells demonstrated enhanced anti-tumor efficiency. These results suggest potential clinical applications of the obtained safe spongosome formulations. Copyright © 2017 Elsevier B.V. All rights reserved.

Nucleoside-Lipid-Based Nanocarriers for Sorafenib Delivery

NASA Astrophysics Data System (ADS)

Benizri, Sebastien; Ferey, Ludivine; Alies, Bruno; Mebarek, Naila; Vacher, Gaelle; Appavoo, Ananda; Staedel, Cathy; Gaudin, Karen; Barthélémy, Philippe

2018-01-01

Although the application of sorafenib, a small inhibitor of tyrosine protein kinases, to cancer treatments remains a worldwide option in chemotherapy, novel strategies are needed to address the low water solubility (< 5 μM), toxicity, and side effects issues of this drug. In this context, the use of nanocarriers is currently investigated in order to overcome these drawbacks. In this contribution, we report a new type of sorafenib-based nanoparticles stabilized by hybrid nucleoside-lipids. The solid lipid nanoparticles (SLNs) showed negative or positive zeta potential values depending on the nucleoside-lipid charge. Transmission electron microscopy of sorafenib-loaded SLNs revealed parallelepiped nanoparticles of about 200 nm. Biological studies achieved on four different cell lines, including liver and breast cancers, revealed enhanced anticancer activities of Sorafenib-based SLNs compared to the free drug. Importantly, contrast phase microscopy images recorded after incubation of cancer cells in the presence of SLNs at high concentration in sorafenib (> 80 μM) revealed a total cancer cell death in all cases. These results highlight the potential of nucleoside-lipid-based SLNs as drug delivery systems.

Recognition of anaerobic bacterial isolates in vitro using electronic nose technology.

PubMed

Pavlou, A; Turner, A P F; Magan, N

2002-01-01

Use of an electronic nose (e.nose) system to differentiation between anaerobic bacteria grown in vitro on agar media. Cultures of Clostridium spp. (14 strains) and Bacteroides fragilis (12 strains) were grown on blood agar plates and incubated in sampling bags for 30 min before head space analysis of the volatiles. Qualitative analyses of the volatile production patterns was carried out using an e.nose system with 14 conducting polymer sensors. Using data analysis techniques such as principal components analysis (PCA), genetic algorithms and neural networks it was possible to differentiate between agar blanks and individual species which accounted for all the data. A total of eight unknowns were correctly discriminated into the bacterial groups. This is the first report of in vitro complex volatile pattern recognition and differentiation of anaerobic pathogens. These results suggest the potential for application of e.nose technology in early diagnosis of microbial pathogens of medical importance.

Development of mannose-anchored thiolated amphotericin B nanocarriers for treatment of visceral leishmaniasis.

PubMed

Shahnaz, Gul; Edagwa, Benson J; McMillan, JoEllyn; Akhtar, Sohail; Raza, Abida; Qureshi, Naveeda A; Yasinzai, Masoom; Gendelman, Howard E

2017-01-01

Our goal was to improve treatment outcomes for visceral leishmaniasis by designing nanocarriers that improve drug biodistribution and half-life. Thus, long-acting mannose-anchored thiolated chitosan amphotericin B nanocarrier complexes (MTC AmB) were developed and characterized. A mannose-anchored thiolated chitosan nanocarrier was manufactured and characterized. MTC AmB was examined for cytotoxicity, biocompatibility, uptake and antimicrobial activities. MTC AmB was rod shaped with a size of 362 nm. MTC AmB elicited 90% macrophage viability and 71-fold enhancement in drug uptake compared with native drug. The antileishmanial IC 50 for MTC AmB was 0.02 μg/ml compared with 0.26 μg/ml for native drug. These studies show that MTC can serve as a platform for clearance of Leishmania in macrophages.

Active Targeted Drug Delivery for Microbes Using Nano-Carriers

PubMed Central

Lin, Yung-Sheng; Lee, Ming-Yuan; Yang, Chih-Hui; Huang, Keng-Shiang

2015-01-01

Although vaccines and antibiotics could kill or inhibit microbes, many infectious diseases remain difficult to treat because of acquired resistance and adverse side effects. Nano-carriers-based technology has made significant progress for a long time and is introducing a new paradigm in drug delivery. However, it still has some challenges like lack of specificity toward targeting the infectious site. Nano-carriers utilized targeting ligands on their surface called ‘active target’ provide the promising way to solve the problems like accelerating drug delivery to infectious areas and preventing toxicity or side-effects. In this mini review, we demonstrate the recent studies using the active targeted strategy to kill or inhibit microbes. The four common nano-carriers (e.g. liposomes, nanoparticles, dendrimers and carbon nanotubes) delivering encapsulated drugs are introduced. PMID:25877093

Pharmaceutical and biomedical applications of lipid-based nanocarriers.

PubMed

Carbone, Claudia; Leonardi, Antonio; Cupri, Sarha; Puglisi, Giovanni; Pignatello, Rosario

2014-03-01

Increasing attention is being given to lipid nanocarriers (LNs) as drug delivery systems, due to the advantages offered of a higher biocompatibility and lower toxicity compared with polymeric nanoparticles. Many administration routes are being investigated for LNs, including topical, oral and parenteral ones. LNs are also proposed for specific applications such as cancer treatment, gene therapy, diagnosis and medical devices production. However, the high number of published research articles does not match an equal amount of patents. A recent Review of ours, published in Pharmaceutical Patent Analyst, reported the patents proposing novel methods for the production of LNs. This review work discusses recent patents, filed in 2007-2013 and dealing with the industrial applications of lipid-based nanocarriers for the vectorization of therapeutically relevant molecules, as well as biotech products such as proteins, gene material and vaccines, in the pharmaceutical, diagnostic and biomedical areas.

Detection of Off-Flavor in Catfish Using a Conducting Polymer Electronic-Nose Technology

PubMed Central

Wilson, Alphus D.; Oberle, Charisse S.; Oberle, Daniel F.

2013-01-01

The Aromascan A32S conducting polymer electronic nose was evaluated for the capability of detecting the presence of off-flavor malodorous compounds in catfish meat fillets to assess meat quality for potential merchantability. Sensor array outputs indicated that the aroma profiles of good-flavor (on-flavor) and off-flavor fillets were strongly different as confirmed by a Principal Component Analysis (PCA) and a Quality Factor value (QF > 7.9) indicating a significant difference at (P < 0.05). The A32S e-nose effectively discriminated between good-flavor and off-flavor catfish at high levels of accuracy (>90%) and with relatively low rates (≤5%) of unknown or indecisive determinations in three trials. This A32S e-nose instrument also was capable of detecting the incidence of mild off-flavor in fillets at levels lower than the threshold of human olfactory detection. Potential applications of e-nose technologies for pre- and post-harvest management of production and meat-quality downgrade problems associated with catfish off-flavor are discussed. PMID:24287526

Toxicity and Carcinogenicity Studies of Ginkgo biloba extract in Rat and Mouse: Liver, Thyroid, and Nose are Targets

PubMed Central

Rider, Cynthia V.; Nyska, Abraham; Cora, Michelle C.; Kissling, Grace E.; Smith, Cynthia; Travlos, Gregory S.; Hejtmancik, Milton R.; Fomby, Laurene M.; Colleton, Curtis A.; Ryan, Michael J.; Kooistra, Linda; Morrison, James P.; Chan, Po C.

2014-01-01

Ginkgo biloba extract (GBE) is a popular herbal supplement that is used to improve circulation and brain function. In spite of widespread human exposure to relatively high doses over potentially long periods of time, there is a paucity of data from animal studies regarding the toxicity and carcinogenicity associated with GBE. In order to fill this knowledge gap, three-month and two-year toxicity and carcinogenicity studies with GBE administered by oral gavage to B6C3F1/N mice and F344/N rats were performed as part of the National Toxicology Program’s Dietary Supplements and Herbal Medicines Initiative. The targets of GBE treatment were the liver, thyroid, and nose. These targets were consistent across exposure period, sex, and species, albeit with varying degrees of effect observed among studies. Key findings included a notably high incidence of hepatoblastomas in male and female mice and evidence of carcinogenic potential in the thyroid gland of both mice and rats. Various nonneoplastic lesions were observed beyond control levels in the liver, thyroid gland, and nose of rats and mice administered GBE. Although these results cannot be directly extrapolated to humans, the findings fill an important data gap in assessing risk associated with GBE use. PMID:23960164

Polymer Nanocarriers to Enhance the Efficiency of Platinum-Based Chemotherapeutics

NASA Astrophysics Data System (ADS)

Callari, Manuela

The aim of this Thesis was to design and prepare polymer nanocarriers capable of encapsulating, carrying and delivering platinum-based chemotherapeutics. Polymer nanocarrier have been widely studied and employed as platinum drug delivery systems with the primary scope to overcome limitations presented by platinum-based chemotherapeutics. The conjugation of platinum onto polymers, however, presents some challenges, and, although there has been great progress in the field of drug delivery in the past years, to date only three polymer nanocarriers for platinum drugs have found their way to the clinic. In this Thesis, hydrophilic block copolymers were synthesised via reversible addition fragmentation chain transfer (RAFT) polymerisation or N-carboxyanhydride ring-opening polymerization (NCA-ROP). Upon attachment of a hydrophobic platinum drug the block copolymer becomes amphiphilic and can self-assemble in aqueous media into nanoparticles of different morphology depending on the block copolymer features. Spherical micelles consisting of a poly(methacrylic acid) core which conjugates and encapsulates the platinum chemotherapeutic and a hydrophilic shell made of sugar blocks were prepared and their biological activities compared in vitro. Among the sugars considered here, fructose based micelles showed promising results in terms of their targeting ability towards breast cancer cells. Consequently, fructose-shelled micelles were selected to explore the effect of different loading quantities of platinum drug. It was discovered that the amount of platinum in the core of the micelle highly influences the internal morphology of the micelle which, in turn, affects the micelle-cell interactions. Micelles with low dual drug loading had better cellular uptake and higher toxicity than the micelles with high drug loading, despite having the same fructose-based outer shell. Interestingly, this aspect had been neglected by literature so far, and is important to explore. Micelles made

The Gendered Nose and its Lack: “Medieval” Nose-Cutting and its Modern Manifestations

PubMed Central

Skinner, Patricia

2014-01-01

Time magazine’s cover photograph in August 2010 of a noseless Afghan woman beside the emotive strap line, “What happens if we leave Afghanistan,” fuelled debate about the “medieval” practices of the Taliban, whose local commander had instructed her husband to take her nose and ears. Press reports attributed the violence to the Pashtun tradition that a dishonored husband “lost his nose.” This equation of nose-cutting with tradition begs questions not only about the Orientalist lens of the western press when viewing Afghanistan, but also about the assumption that the word “medieval” can function as a label for such practices. A study of medieval nose-cutting suggests that its identification as an “eastern” practice should be challenged. Rather clearer is its connection with patriarchal values of authority and honor: the victims of such punishment have not always been women, but this is nevertheless a gendered punishment of the powerless by the powerful. PMID:24790391

Foreign body in the nose

MedlinePlus

... such as marbles), crayon pieces, erasers, paper wads, cotton, beads, button batteries, and disc magnets. A foreign ... DO NOT search the nose with cotton swabs or other tools. This may ... into the nose. DO NOT use tweezers or other tools to remove ...

Thermodynamic and Kinetic Aspects Involved in the Development of Nanocarriers and Drug Delivery Systems Based on Cationic Biopolymers.

PubMed

Bianco, Ismael D; Alasino, Roxana V; Leonhard, Victoria; Beltramo, Dante M

2016-01-01

During the last years we have seen an increasing number of reports describing new properties and potential applications of cationic polymers and derived nanostructures. This review gives a summary of their applications in drug delivery, the preparation methods for nano and microstructures and will attempt to give a glimpse on how their structure, chemical composition and properties may be affected or modulated as to make them suitable for an intended application as drug delivery nanocarriers. The compositional complexity with the existence of several reacting groups makes cationic nanostructures critically sensitive to the contribution of thermodynamic and kinetic parameters in the determination of the type and stability of a particular structure and its ability to respond to changes in environmental conditions in the right time frame. Curiously, and contrarily to what could be expected, despite the fact that cationic polymers can form strong electrostatic interactions the contribution of the entropic component has been often found to be very important for their association with negatively charged supramolecular structures. Some general considerations indicate that when considering a complex multimolecular system like a nanocarrier containing an active ingredient it is frequently possible to find conditions under which enthalpic and entropic contributions are compensated leading to stable structures with a marginal thermodynamic stability (free energy change close to zero) which make them able to respond relatively fast to changes in the environmental conditions and therefore suitable for the design of smart drug delivery systems. Like with other nanocarriers, it should always be kept in mind that the properties of cationic nanocarriers will depend not only on their chemical composition but also on the properties of the structures formed by them.

The effect of size and polymer architecture of doxorubicin-poly(ethylene) glycol conjugate nanocarriers on breast duct retention, potency and toxicity.

PubMed

Gu, Zichao; Gao, Dayuan; Al-Zubaydi, Firas; Li, Shike; Singh, Yashveer; Rivera, Kristia; Holloway, Jennifer; Szekely, Zoltan; Love, Susan; Sinko, Patrick J

2018-04-23

��h, which was significantly shorter than that of the linear and branched 40 kDa PEG-DOX nanocarriers. Increased molecular weight and decreased branching both demonstrated a strong correlation to enhanced mammary gland retention. Intraductally administered free doxorubicin resulted in ductal damage, severe inflammation and generation of atypical cell neoplasms, whereas PEG-DOX nanocarriers induced only minor and transient inflammation (i.e., damaged epithelial cells and detached cellular debris). The 40 kDa 4-arm PEG-DOX nanocarrier demonstrated the longest ductal retention half-life, the lowest IC 50 (i.e., most potent), and minimal ductal damage and inflammation. The current results suggest that PEG-DOX nanocarriers with prolonged ductal retention may present the best option for intraductal treatment of DCIS, due to their low local toxicity and potential for sustained therapeutic effect. Copyright © 2017. Published by Elsevier B.V.

Lipid nanocarriers and molecular targets for malaria chemotherapy.

PubMed

Jain, Kunal; Sood, Sumeet; Gowthamarajan, Kuppusamy

2014-03-01

Malaria is the most serious tropical disease of humankind and a cause of much debilitation and morbidity throughout the world especially in endemic areas like India and Africa. The development of drug resistance may be due to insufficient drug concentration in presence of high parasite load. In addition, the present pharmaceutical dosage forms are ineffective thereby necessitating the development of novel dosage forms which are effective, safe and affordable to underprivileged population of the developing world. The rapid advancement of nanotechnology has raised the possibility of using lipid nanocarriers that interact within biological environment for treatment of infectious diseases. Thus, lipid based nano-delivery systems offer a platform to formulate old and toxic antimalarial drugs thereby modifying their pharmacokinetic profile, biodistribution and targetability. Further, there is a need to develop new chemotherapy based approaches for inhibiting the parasite-specific metabolic pathways. The present review highlights the advances in lipid nanocarriers and putative molecular targets for antimalarial chemotherapy.

Development of mannose-anchored thiolated amphotericin B nanocarriers for treatment of visceral leishmaniasis

PubMed Central

Shahnaz, Gul; Edagwa, Benson J; McMillan, JoEllyn; Akhtar, Sohail; Raza, Abida; Qureshi, Naveeda A; Yasinzai, Masoom; Gendelman, Howard E

2017-01-01

Aim: Our goal was to improve treatment outcomes for visceral leishmaniasis by designing nanocarriers that improve drug biodistribution and half-life. Thus, long-acting mannose-anchored thiolated chitosan amphotericin B nanocarrier complexes (MTC AmB) were developed and characterized. Materials & methods: A mannose-anchored thiolated chitosan nanocarrier was manufactured and characterized. MTC AmB was examined for cytotoxicity, biocompatibility, uptake and antimicrobial activities. Results: MTC AmB was rod shaped with a size of 362 nm. MTC AmB elicited 90% macrophage viability and 71-fold enhancement in drug uptake compared with native drug. The antileishmanial IC50 for MTC AmB was 0.02 μg/ml compared with 0.26 μg/ml for native drug. Conclusion: These studies show that MTC can serve as a platform for clearance of Leishmania in macrophages. PMID:27879160

Satratoxin G from the Black Mold Stachybotrys chartarum Evokes Olfactory Sensory Neuron Loss and Inflammation in the Murine Nose and Brain

PubMed Central

Islam, Zahidul; Harkema, Jack R.; Pestka, James J.

2006-01-01

Satratoxin G (SG) is a macrocyclic trichothecene mycotoxin produced by Stachybotrys chartarum, the “black mold” suggested to contribute etiologically to illnesses associated with water-damaged buildings. Using an intranasal instillation model in mice, we found that acute SG exposure specifically induced apoptosis of olfactory sensory neurons (OSNs) in the olfactory epithelium. Dose–response analysis revealed that the no-effect and lowest-effect levels at 24 hr postinstillation (PI) were 5 and 25 μg/kg body weight (bw) SG, respectively, with severity increasing with dose. Apoptosis of OSNs was identified using immunohistochemistry for caspase-3 expression, electron microscopy for ultrastructural cellular morphology, and real-time polymerase chain reaction for elevated expression of the proapoptotic genes Fas, FasL, p75NGFR, p53, Bax, caspase-3, and CAD. Time-course studies with a single instillation of SG (500 μg/kg bw) indicated that maximum atrophy of the olfactory epithelium occurred at 3 days PI. Exposure to lower doses (100 μg/kg bw) for 5 consecutive days resulted in similar atrophy and apoptosis, suggesting that in the short term, these effects are cumulative. SG also induced an acute, neutrophilic rhinitis as early as 24 hr PI. Elevated mRNA expression for the proinflammatory cytokines tumor necrosis factor-α, interleukin-6 (IL-6), and IL-1 and the chemokine macrophage-inflammatory protein-2 (MIP-2) were detected at 24 hr PI in both the ethmoid turbinates of the nasal airways and the adjacent olfactory bulb of the brain. Marked atrophy of the olfactory nerve and glomerular layers of the olfactory bulb was also detectable by 7 days PI along with mild neutrophilic encephalitis. These findings suggest that neurotoxicity and inflammation within the nose and brain are potential adverse health effects of exposure to satratoxins and Stachybotrys in the indoor air of water-damaged buildings. PMID:16835065

Satratoxin G from the black mold Stachybotrys chartarum evokes olfactory sensory neuron loss and inflammation in the murine nose and brain.

PubMed

Islam, Zahidul; Harkema, Jack R; Pestka, James J

2006-07-01

Satratoxin G (SG) is a macrocyclic trichothecene mycotoxin produced by Stachybotrys chartarum, the "black mold" suggested to contribute etiologically to illnesses associated with water-damaged buildings. Using an intranasal instillation model in mice, we found that acute SG exposure specifically induced apoptosis of olfactory sensory neurons (OSNs) in the olfactory epithelium. Dose-response analysis revealed that the no-effect and lowest-effect levels at 24 hr postinstillation (PI) were 5 and 25 microg/kg body weight (bw) SG, respectively, with severity increasing with dose. Apoptosis of OSNs was identified using immunohistochemistry for caspase-3 expression, electron microscopy for ultrastructural cellular morphology, and real-time polymerase chain reaction for elevated expression of the proapoptotic genes Fas, FasL, p75NGFR, p53, Bax, caspase-3, and CAD. Time-course studies with a single instillation of SG (500 microg/kg bw) indicated that maximum atrophy of the olfactory epithelium occurred at 3 days PI. Exposure to lower doses (100 microg/kg bw) for 5 consecutive days resulted in similar atrophy and apoptosis, suggesting that in the short term, these effects are cumulative. SG also induced an acute, neutrophilic rhinitis as early as 24 hr PI. Elevated mRNA expression for the proinflammatory cytokines tumor necrosis factor-alpha, interleukin-6 (IL-6) , and IL-1 and the chemokine macrophage-inflammatory protein-2 (MIP-2) were detected at 24 hr PI in both the ethmoid turbinates of the nasal airways and the adjacent olfactory bulb of the brain. Marked atrophy of the olfactory nerve and glomerular layers of the olfactory bulb was also detectable by 7 days PI along with mild neutrophilic encephalitis. These findings suggest that neurotoxicity and inflammation within the nose and brain are potential adverse health effects of exposure to satratoxins and Stachybotrys in the indoor air of water-damaged buildings.

Vascular-targeted nanocarriers: design considerations and strategies for successful treatment of atherosclerosis and other vascular diseases.

PubMed

Kelley, William J; Safari, Hanieh; Lopez-Cazares, Genesis; Eniola-Adefeso, Omolola

2016-11-01

Vascular-targeted nanocarriers are an attractive option for the treatment of a number of cardiovascular diseases, as they allow for more specific delivery and increased efficacy of many small molecule drugs. However, immune clearance, limited cellular uptake, and particle-cell dynamics in blood flow can hinder nanocarrier efficacy in many applications. This review aims to investigate successful strategies for the use of vascular-targeted nanocarriers in the treatment of cardiovascular diseases such as atherosclerosis. In particular, the review will highlight strategies employed for actively targeting the components of the atherosclerotic plaque, including endothelial cells, macrophages, and platelets and passive targeting via endothelial permeability, as well as design specifications (such as size, shape, and density) aimed at enhancing the ability of nanocarriers to reach the vascular wall. WIREs Nanomed Nanobiotechnol 2016, 8:909-926. doi: 10.1002/wnan.1414 For further resources related to this article, please visit the WIREs website. © 2016 Wiley Periodicals, Inc.

Electronic-Nose Applications for Fruit Identification, Ripeness and Quality Grading

PubMed Central

Baietto, Manuela; Wilson, Alphus D.

2015-01-01

Fruits produce a wide range of volatile organic compounds that impart their characteristically distinct aromas and contribute to unique flavor characteristics. Fruit aroma and flavor characteristics are of key importance in determining consumer acceptance in commercial fruit markets based on individual preference. Fruit producers, suppliers and retailers traditionally utilize and rely on human testers or panels to evaluate fruit quality and aroma characters for assessing fruit salability in fresh markets. We explore the current and potential utilization of electronic-nose devices (with specialized sensor arrays), instruments that are very effective in discriminating complex mixtures of fruit volatiles, as new effective tools for more efficient fruit aroma analyses to replace conventional expensive methods used in fruit aroma assessments. We review the chemical nature of fruit volatiles during all stages of the agro-fruit production process, describe some of the more important applications that electronic nose (e-nose) technologies have provided for fruit aroma characterizations, and summarize recent research providing e-nose data on the effectiveness of these specialized gas-sensing instruments for fruit identifications, cultivar discriminations, ripeness assessments and fruit grading for assuring fruit quality in commercial markets. PMID:25569761

The blood-brain barrier and nasal drug delivery to the central nervous system.

PubMed

Miyake, Marcel Menon; Bleier, Benjamin S

2015-01-01

The blood-brain barrier (BBB) is a highly efficient system that separates the central nervous system (CNS) from general circulation and promotes selective transport of molecules that are essential for brain function. However, it also limits the distribution of systemically administered therapeutics to the brain; therefore, there is a restricted number of drugs available for the treatment of brain disorders. Several drug-targeting strategies have been developed to attempt to bypass the BBB, but none has proved sufficiently effective in reaching the brain. The objective of this study is to generally review these strategies of drug administration to the CNS. Noninvasive methods of drug delivery, such as chemical and biologic transport systems, do not represent a feasible platform, whereas for most drugs, it is still not possible to achieve therapeutic levels within the brain tissue after intravenous or oral administration, and the use of higher potency or more concentrated doses may cause serious toxic side effects. Direct intrathecal drug delivery through a catheter into the CNS also presents several problems. Intranasal drug delivery is a potential alternative method due to the direct transport into the cerebrospinal fluid (CSF) compartment along the olfactory pathway, but the study's conclusions are controversial. An endoscopic intranasal surgical procedure using established skull base surgery reconstruction techniques based on the use of a nasal mucosa surgical flap as the only obstacle between the nose and the subarachnoid space has appeared as a potential solution to increase the absorption of intranasal drugs to the CNS. Despite extensive efforts to develop new techniques to cross the BBB, none has proved sufficiently effective in reaching the brain, whereas minimizing adverse effects and the endoscopic mucosal grafting technique offers new potential promise.

A novel Trojan-horse targeting strategy to reduce the non-specific uptake of nanocarriers by non-cancerous cells.

PubMed

Shen, Zheyu; Wu, Hao; Yang, Sugeun; Ma, Xuehua; Li, Zihou; Tan, Mingqian; Wu, Aiguo

2015-11-01

One big challenge with active targeting of nanocarriers is non-specific binding between targeting molecules and non-target moieties expressed on non-cancerous cells, which leads to non-specific uptake of nanocarriers by non-cancerous cells. Here, we propose a novel Trojan-horse targeting strategy to hide or expose the targeting molecules of nanocarriers on-demand. The non-specific uptake by non-cancerous cells can be reduced because the targeting molecules are hidden in hydrophilic polymers. The nanocarriers are still actively targetable to cancer cells because the targeting molecules can be exposed on-demand at tumor regions. Typically, Fe3O4 nanocrystals (FN) as magnetic resonance imaging (MRI) contrast agents were encapsulated into albumin nanoparticles (AN), and then folic acid (FA) and pH-sensitive polymers (PP) were grafted onto the surface of AN-FN to construct PP-FA-AN-FN nanoparticles. Fourier transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS), transmission electron microscope (TEM) and gel permeation chromatography (GPC) results confirm successful construction of PP-FA-AN-FN. According to difference of nanoparticle-cellular uptake between pH 7.4 and 5.5, the weight ratio of conjugated PP to nanoparticle FA-AN-FN (i.e. graft density) and the molecular weight of PP (i.e. graft length) are optimized to be 1.32 and 5.7 kDa, respectively. In vitro studies confirm that the PP can hide ligand FA to prevent it from binding to cells with FRα at pH 7.4 and shrink to expose FA at pH 5.5. In vivo studies demonstrate that our Trojan-horse targeting strategy can reduce the non-specific uptake of the PP-FA-AN-FN by non-cancerous cells. Therefore, our PP-FA-AN-FN might be used as an accurately targeted MRI contrast agent. Copyright © 2015 Elsevier Ltd. All rights reserved.

Your Nose

MedlinePlus

... the space behind your nose) is the olfactory epithelium (say: ol-FAK-tuh-ree eh-puh-THEE- ... that has to do with smelling. The olfactory epithelium contains special receptors that are sensitive to odor ...

Specific targeting and noninvasive magnetic resonance imaging of an asthma biomarker in the lung using polyethylene glycol functionalized magnetic nanocarriers.

PubMed

Al Faraj, Achraf; Shaik, Asma Sultana; Afzal, Sibtain; Al-Muhsen, Saleh; Halwani, Rabih

2016-05-01

Simultaneous inhibition of IL4 and IL13 via the common receptor chain IL4Rα to block adequately their biologic effects presents a promising therapeutic approach to give the additional relief required for asthma patients. In this study, superparamagnetic iron oxide nanoparticles were conjugated with anti-IL4Rα blocking antibodies via polyethylene glycol (PEG) polymers. The delivery of these blocking antibodies to the inflammatory sites in the lung via the developed nanocarriers was assessed using noninvasive free-breathing pulmonary MRI. Biocompatibility assays confirmed the safety of the developed nanocarriers for pre-clinical investigations. For all the investigated formulations, nanocarriers were found to be very stable at neutral pH. However, the stability noticeably decreased with the PEG length in acidic environment and thus the loaded antibodies were preferentially released. Immunofluorescence and fluorimetry assays confirmed the binding of the nanocarriers to the IL4Rα asthma biomarker. Pulmonary MRI performed using an ultra-short echo time sequence allowed simultaneous noninvasive monitoring of inflammatory responses induced by ovalbumin challenge and tracking of the developed nanocarriers, which were found to colocalize with the inflammatory sites in the lung. Targeting of the developed nanocarriers to areas rich in IL4Rα positive inflammatory cells was confirmed using histological and flow cytometry analyses. The anti-IL4Rα-conjugated nanocarriers developed here have been confirmed to be efficient in targeting key inflammatory cells during chronic lung inflammation following intrapulmonary administration. Targeting efficiency was monitored using noninvasive MRI, allowing detection of the nanocarriers' colocalizations with the inflammatory sites in the lung of ovalbumin-challenged asthmatic mice. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Fluorescent carbon dots as an efficient siRNA nanocarrier for its interference therapy in gastric cancer cells.

PubMed

Wang, Qing; Zhang, Chunlei; Shen, Guangxia; Liu, Huiyang; Fu, Hualin; Cui, Daxiang

2014-12-30

Fluorescent carbon dots (Cdots) have attracted increasing attention due to their potential applications in sensing, catalysis, and biomedicine. Currently, intensive research has been concentrated on the synthesis and imaging-guided therapy of these benign photoluminescent materials. Meanwhile, Cdots have been explored as nonviral vector for nucleic acid or drug delivery by chemical modification on purpose. We have developed a microwave assisted one-step synthesis of Cdots with citric acid as carbon source and tryptophan (Trp) as both nitrogen source and passivation agent. The Cdots with uniform size show superior water solubility, excellent biocompatibility, and high quantum yield. Afterwards, the PEI (polyethylenimine)-adsorbed Cdots nanoparticles (Cdots@PEI) were applied to deliver Survivin siRNA into human gastric cancer cell line MGC-803. The results have confirmed the nanocarrier exhibited excellent biocompatibility and a significant increase in cellular delivery of siRNA, inducing efficient knockdown for Survivin protein to 6.1%. In addition, PEI@Cdots complexes mediated Survivin silencing, the arrested cell cycle progression in G1 phase as well as cell apoptosis was observed. The Cdots-based and PEI-adsorbed complexes both as imaging agents and siRNA nanocarriers have been developed for Survivin siRNA delivery. And the results indicate that Cdots-based nanocarriers could be utilized in a broad range of siRNA delivery systems for cancer therapy.

Recent advances in electronic nose techniques for monitoring of fermentation process.

PubMed

Jiang, Hui; Zhang, Hang; Chen, Quansheng; Mei, Congli; Liu, Guohai

2015-12-01

Microbial fermentation process is often sensitive to even slight changes of conditions that may result in unacceptable end-product quality. Thus, the monitoring of the process is critical for discovering unfavorable deviations as early as possible and taking the appropriate measures. However, the use of traditional analytical techniques is often time-consuming and labor-intensive. In this sense, the most effective way of developing rapid, accurate and relatively economical method for quality assurance in microbial fermentation process is the use of novel chemical sensor systems. Electronic nose techniques have particular advantages in non-invasive monitoring of microbial fermentation process. Therefore, in this review, we present an overview of the most important contributions dealing with the quality control in microbial fermentation process using the electronic nose techniques. After a brief description of the fundamentals of the sensor techniques, some examples of potential applications of electronic nose techniques monitoring are provided, including the implementation of control strategies and the combination with other monitoring tools (i.e. sensor fusion). Finally, on the basis of the review, the electronic nose techniques are critically commented, and its strengths and weaknesses being highlighted. In addition, on the basis of the observed trends, we also propose the technical challenges and future outlook for the electronic nose techniques.

Delivery of acid sphingomyelinase in normal and niemann-pick disease mice using intercellular adhesion molecule-1-targeted polymer nanocarriers.

PubMed

Garnacho, Carmen; Dhami, Rajwinder; Simone, Eric; Dziubla, Thomas; Leferovich, John; Schuchman, Edward H; Muzykantov, Vladimir; Muro, Silvia

2008-05-01

Type B Niemann-Pick disease (NPD) is a multiorgan system disorder caused by a genetic deficiency of acid sphingomyelinase (ASM), for which lung is an important and challenging therapeutic target. In this study, we designed and evaluated new delivery vehicles for enzyme replacement therapy of type B NPD, consisting of polystyrene and poly(lactic-coglycolic) acid polymer nanocarriers targeted to intercellular adhesion molecule (ICAM)-1, an endothelial surface protein up-regulated in many pathologies, including type B NPD. Real-time vascular imaging using intravital microscopy and postmortem imaging of mouse organs showed rapid, uniform, and efficient binding of fluorescently labeled ICAM-1-targeted ASM nanocarriers (anti-ICAM/ASM nanocarriers) to endothelium after i.v. injection in mice. Fluorescence microscopy of lung alveoli actin, tissue histology, and 125I-albumin blood-to-lung transport showed that anti-ICAM nanocarriers cause neither detectable lung injury, nor abnormal vascular permeability in animals. Radioisotope tracing showed rapid disappearance from the circulation and enhanced accumulation of anti-ICAM/125I-ASM nanocarriers over the nontargeted naked enzyme in kidney, heart, liver, spleen, and primarily lung, both in wild-type and ASM knockout mice. These data demonstrate that ICAM-1-targeted nanocarriers may enhance enzyme replacement therapy for type B NPD and perhaps other lysosomal storage disorders.

DNA Dendrimer: An Efficient Nanocarrier of Functional Nucleic Acids for Intracellular Molecular Sensing

PubMed Central

2015-01-01

Functional nucleic acid (FNA)-based sensing systems have been developed for efficient detection of a wide range of biorelated analytes by employing DNAzymes or aptamers as recognition units. However, their intracellular delivery has always been a concern, mainly in delivery efficiency, kinetics, and the amount of delivered FNAs. Here we report a DNA dendrimer scaffold as an efficient nanocarrier to deliver FNAs and to conduct in situ monitoring of biological molecules in living cells. A histidine-dependent DNAzyme and an anti-ATP aptamer were chosen separately as the model FNAs to make the FNA dendrimer. The FNA-embedded DNA dendrimers maintained the catalytic activity of the DNAzyme or the aptamer recognition function toward ATP in the cellular environment, with no change in sensitivity or specificity. Moreover, these DNA dendrimeric nanocarriers show excellent biocompatibility, high intracellular delivery efficiency, and sufficient stability in a cellular environment. This FNA dendrimeric nanocarrier may find a broad spectrum of applications in biomedical diagnosis and therapy. PMID:24806614

Engineered, thermoresponsive, magnetic nanocarriers of oligo(ethylene glycol)-methacrylate-based biopolymers

NASA Astrophysics Data System (ADS)

McCallister, Thomas; Gidney, Elwood; Adams, Devin; Diercks, David R.; Ghosh, Santaneel

2014-11-01

Engineered magnetic nanocarriers offer attractive options for implementing novel therapeutic solutions in biomedical research; however lack of biocompatibility and external tunability have prevented a biomedical breakthrough. Here we report multifunctional, magnetic nanospheres with tailored size, volumetric transition range, and magnetic properties based on biocompatible, thermo-responsive oligo(ethylene glycol) methacrylate biopolymers. Precise control of the nanosphere size in the range 100-300 nm, coupled with a higher and broader volumetric transition range (32-42 °C), is ideal for various biomedical applications. More importantly, super-paramagnetic behavior of the nanocarriers, even after polymer shell shrinkage, indicates stable and easily controllable loss mechanisms under exposure to an ac magnetic field.

Carbohydrate coated, folate functionalized colloidal graphene as a nanocarrier for both hydrophobic and hydrophilic drugs.

PubMed

Maity, Amit Ranjan; Chakraborty, Atanu; Mondal, Avijit; Jana, Nikhil R

2014-03-07

Although graphene based drug delivery has gained significant recent interest, the synthesis of colloidal graphene based nanocarriers with high drug loading capacities and with targeting ligands at the outer surface is a challenging issue. We have synthesized carbohydrate coated and folate functionalized colloidal graphene which can be used as a nanocarrier for a wide variety of hydrophobic and hydrophilic drugs. The synthesized colloidal graphene is loaded with paclitaxol, camptothecin, doxorubicin, curcumin and used for their targeted delivery to cancer cells. We demonstrate that this drug loaded functional graphene nanocarrier can successfully deliver drugs into target cells and offers an enhanced therapeutic performance. The reported approach can be extended to the cellular delivery of other hydrophobic and hydrophilic drugs and the simultaneous delivery of multiple drugs.

Assembling of multifunctional latex-based hybrid nanocarriers from Calotropis gigantea for sustained (doxorubicin) DOX releases.

PubMed

Pradeepkumar, Periyakaruppan; Govindaraj, Dharman; Jeyaraj, Murugaraj; Munusamy, Murugan A; Rajan, Mariappan

2017-03-01

Natural rubber Latex (Lax) is a colloidal dispersion of polymer particles in liquid and shows good biodegradable, biocompatibility, and non-toxicity. Natural polymers are the most important materials used in food packaging, micro/nano-drug delivery, tissue engineering, agriculture, and coating. In the present study, natural compounds extracted from plant Lax were designed to function as drug carriers using various surfactants via emulation and solvent evaporation method. Calotropis gigantea belongs to the family Apocynaceae and has received considerable attention in modern medicine, ayurvedeic, siddha, and traditional medicine. Since, we were isolated biodegradable, non-toxic, and biocompatible materials as latex from Calotropis gigantea plant. The Lax was separated as per their solubility nature and it was designed as a carrier using surfactant namely; Sorbitanmonolaurate (Span-20), sodium lauryl sulfate (SLS), and cetyltrimethylammonium bromide (CTAB). The isolated compounds from Lax of Calotropis gigantea were analyzed using high-performance liquid chromatography. To confirm the encapsulation efficiency and in vitro drug release of the carriers, doxorubicin (DOX) was used as a model natural drug. The hybrid nanocarriers were successfully synthesized through simple solvent evaporation using three surfactants, and the morphology was characterized by SEM and TEM technique. The functionality and crystalline nature of the nanocarriers were confirmed using FTIR and XRD, respectively. Within 90min, the maximum amount of DOX was encapsulated in the carriers, and prolonged cumulative drug release by the nanocarriers was observed. The formulated natural carriers were found to have potentially effective cytotoxic effects on lung cancer cells. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Impact of Particle Size and Polydispersity Index on the Clinical Applications of Lipidic Nanocarrier Systems.

PubMed

Danaei, M; Dehghankhold, M; Ataei, S; Hasanzadeh Davarani, F; Javanmard, R; Dokhani, A; Khorasani, S; Mozafari, M R

2018-05-18

Lipid-based drug delivery systems, or lipidic carriers, are being extensively employed to enhance the bioavailability of poorly-soluble drugs. They have the ability to incorporate both lipophilic and hydrophilic molecules and protecting them against degradation in vitro and in vivo. There is a number of physical attributes of lipid-based nanocarriers that determine their safety, stability, efficacy, as well as their in vitro and in vivo behaviour. These include average particle size/diameter and the polydispersity index (PDI), which is an indication of their quality with respect to the size distribution. The suitability of nanocarrier formulations for a particular route of drug administration depends on their average diameter, PDI and size stability, among other parameters. Controlling and validating these parameters are of key importance for the effective clinical applications of nanocarrier formulations. This review highlights the significance of size and PDI in the successful design, formulation and development of nanosystems for pharmaceutical, nutraceutical and other applications. Liposomes, nanoliposomes, vesicular phospholipid gels, solid lipid nanoparticles, transfersomes and tocosomes are presented as frequently-used lipidic drug carriers. The advantages and limitations of a range of available analytical techniques used to characterize lipidic nanocarrier formulations are also covered.

Stuffy Nose

MedlinePlus

... release histamine, a chemical which dramatically increases blood flow to the nose and causes nasal tissue to swell. This inflames ... psychological stress, inadequate thyroid function, pregnancy, certain ... of decongesting nasal sprays, and exposure to irritants such as perfumes ...

Applications and Advances in Electronic-Nose Technologies

PubMed Central

Wilson, Alphus D.; Baietto, Manuela

2009-01-01

Electronic-nose devices have received considerable attention in the field of sensor technology during the past twenty years, largely due to the discovery of numerous applications derived from research in diverse fields of applied sciences. Recent applications of electronic nose technologies have come through advances in sensor design, material improvements, software innovations and progress in microcircuitry design and systems integration. The invention of many new e-nose sensor types and arrays, based on different detection principles and mechanisms, is closely correlated with the expansion of new applications. Electronic noses have provided a plethora of benefits to a variety of commercial industries, including the agricultural, biomedical, cosmetics, environmental, food, manufacturing, military, pharmaceutical, regulatory, and various scientific research fields. Advances have improved product attributes, uniformity, and consistency as a result of increases in quality control capabilities afforded by electronic-nose monitoring of all phases of industrial manufacturing processes. This paper is a review of the major electronic-nose technologies, developed since this specialized field was born and became prominent in the mid 1980s, and a summarization of some of the more important and useful applications that have been of greatest benefit to man. PMID:22346690

Targeted Mesoporous Silica Nanocarriers in Oncology.

PubMed

Baeza, Alejandro; Vallet-Regi, Maria

2018-02-08

Cancer is one of the major leading causes of death worldwide and its prevalence will be higher in the coming years due to the progressive aging of the population. The development of nanocarriers in oncology has provided a new hope in the fight against this terrible disease. Among the different types of nanoparticles which have been reported in the scientific literature, mesoporous silica nanoparticles (MSNs) are very promising materials due to their inherent properties such as high loading capacity of many different drugs, excellent biocompatibility and easy functionalization. This review presents the current state of the art related to the development of mesoporous silica nanocarriers for antitumoral therapy paying special attention on targeted MSN able to selectively destroy tumoral cells, reducing the side damage in healthy ones, and the basic principles of targeting tumoral tissues and cells. MSNs constitute a promising nanomaterial for drug delivery applications in antitumoral therapy as a consequence of its unique properties such as excellent biocompatibility, high loading capacity, robustness, easy production and existence of multiple strategies for their functionalization with a myriad of bio-organic moieties. In the coming years, the clever application of this material would provide novel alternatives for the treatment of this complex disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Review of electronic-nose technologies and algorithms to detect hazardous chemicals in the environment

Treesearch

Alphus D. Wilson

2012-01-01

Novel mobile electronic-nose (e-nose) devices and algorithms capable of real-time detection of industrial and municipal pollutants, released from point-sources, recently have been developed by scientists worldwide that are useful for monitoring specific environmental-pollutant levels for enforcement and implementation of effective pollution-abatement programs. E-nose...

Formulation, Quality Control and Safety Issues of Nanocarriers Used for Cancer Treatment.

PubMed

Bianco, Ismael D; Ceballos, Marcelo R; Casado, Cristian; Dabbene, Viviana G; Rizzi, Carolina; Mizutamari, R Kiyomi

2017-01-01

Cancer is becoming a leading cause of death in the last years. Although we have seen great advances, most human cancers remain incurable because many patients either do not respond or relapse to treatment. Several lines of research are disclosing new therapeutic targets which lead to new active drugs. However, there are still unsolved problems related to stabilization of the pharmaceutical ingredient in aqueous and biological media, pharmacokinetic and pharmacodynamic profiles and cellular uptake to name just a few. In this context, nanotechnology with the emerging tools of nanoengineering offers many possibilities to guide the design of new products with improved safety and efficacy. The presence of several reacting groups and the sensitivity of their properties to small changes in composition make nanocarriers tunable not only to modify their stability in a particular environment but also to respond to changes in biological situations in the right place and time frame. This review summarizes the main preparation methods and formulation strategies of nano and microcarriers designed for drug delivery applications for cancer treatment and will attempt to give a glimpse on how their structure, shape, physico-chemical properties and chemical composition may affect their overall stability and interactions with biological systems. We will also cover aspects of nanoengineering that are opening new opportunities for the development of more effective nanomedicines, emphasizing on the challenges that have to be kept in mind when dealing with biological activities of nanocarriers that depend not only on their chemical composition but also on those of the structures formed by them and by their interactions with biological systems. From this, a very important issue that emerges is that nanocarriers frequently display an intrinsic bioactivity (i.e.: immunomodulatory). Therefore, it should be stressed that nanocarriers cannot be considered as inert, biocompatible excipients

Novel Nanotechnologies for Brain Cancer Therapeutics and Imaging.

PubMed

Ferroni, Letizia; Gardin, Chiara; Della Puppa, Alessandro; Sivolella, Stefano; Brunello, Giulia; Scienza, Renato; Bressan, Eriberto; D'Avella, Domenico; Zavan, Barbara

2015-11-01

Despite progress in surgery, radiotherapy, and in chemotherapy, an effective curative treatment of brain cancer, specifically malignant gliomas, does not yet exist. The efficacy of current anti-cancer strategies in brain tumors is limited by the lack of specific therapies against malignant cells. Besides, the delivery of the drugs to brain tumors is limited by the presence of the blood-brain barrier. Nanotechnology today offers a unique opportunity to develop more effective brain cancer imaging and therapeutics. In particular, the development of nanocarriers that can be conjugated with several functional molecules including tumor-specific ligands, anticancer drugs, and imaging probes, can provide new devices which are able to overcome the difficulties of the classical strategies. Nanotechnology-based approaches hold great promise for revolutionizing brain cancer medical treatments, imaging, and diagnosis.

A breath test for malignant mesothelioma using an electronic nose.

PubMed

Chapman, Eleanor A; Thomas, Paul S; Stone, Emily; Lewis, Craig; Yates, Deborah H

2012-08-01

Malignant mesothelioma (MM) is a rare tumour which is difficult to diagnose in its early stages. Earlier detection of MM could potentially improve survival. Exhaled breath sampling of volatile organic compounds (VOCs) using a carbon polymer array (CPA) electronic nose recognises specific breath profiles characteristic of different diseases, and can distinguish between patients with lung cancer and controls. With MM, the potential confounding effect of other asbestos-related diseases (ARDs) needs to be considered. We hypothesised that as CPA electronic nose would distinguish patients with MM, patients with benign ARDs, and controls with high sensitivity and specificity. 20 MM, 18 ARD and 42 control subjects participated in a cross-sectional, case-control study. Breath samples were analysed using the Cyranose 320 (Smiths Detection, Pasadena, CA, USA), using canonical discriminant analysis and principal component reduction. 10 MM subjects created the training set. Smell prints from 10 new MM patients were distinguished from control subjects with an accuracy of 95%. Patients with MM, ARDs and control subjects were correctly identified in 88% of cases. Exhaled breath VOC profiling can accurately distinguish between patients with MM, ARDs and controls using a CPA electronic nose. This could eventually translate into a screening tool for high-risk populations.

Why Rudolph’s nose is red: observational study

PubMed Central

van Kuijen, Anne-Marije; Milstein, Dan M J; Yürük, Koray; Folkow, Lars P; Fokkens, Wytske J; Blix, Arnoldus S

2012-01-01

Objective To characterise the functional morphology of the nasal microcirculation in humans in comparison with reindeer as a means of testing the hypothesis that the luminous red nose of Rudolph, one of the most well known reindeer pulling Santa Claus’s sleigh, is due to the presence of a highly dense and rich nasal microcirculation. Design Observational study. Setting Tromsø, Norway (near the North Pole), and Amsterdam, the Netherlands. Participants Five healthy human volunteers, two adult reindeer, and a patient with grade 3 nasal polyposis. Main outcome measures Architecture of the microvasculature of the nasal septal mucosa and head of the inferior turbinates, kinetics of red blood cells, and real time reactivity of the microcirculation to topical medicines. Results Similarities between human and reindeer nasal microcirculation were uncovered. Hairpin-like capillaries in the reindeers’ nasal septal mucosa were rich in red blood cells, with a perfused vessel density of 20 (SD 0.7) mm/mm2. Scattered crypt or gland-like structures surrounded by capillaries containing flowing red blood cells were found in human and reindeer noses. In a healthy volunteer, nasal microvascular reactivity was demonstrated by the application of a local anaesthetic with vasoconstrictor activity, which resulted in direct cessation of capillary blood flow. Abnormal microvasculature was observed in the patient with nasal polyposis. Conclusions The nasal microcirculation of reindeer is richly vascularised, with a vascular density 25% higher than that in humans. These results highlight the intrinsic physiological properties of Rudolph’s legendary luminous red nose, which help to protect it from freezing during sleigh rides and to regulate the temperature of the reindeer’s brain, factors essential for flying reindeer pulling Santa Claus’s sleigh under extreme temperatures. PMID:23247980

The potential impact of white-nose syndrome on the conservation status of north american bats.

PubMed

Alves, Davi M C C; Terribile, Levi C; Brito, Daniel

2014-01-01

White-Nose syndrome (WNS) is an emergent infectious disease that has already killed around six million bats in North America and has spread over two thousand kilometers from its epicenter. However, only a few studies on the possible impacts of the fungus on bat hosts were conducted, particularly concerning its implications for bat conservation. We predicted the consequences of WNS spread by generating a map with potential areas for its occurrence based on environmental conditions in sites where the disease already occurs, and overlaid it with the geographic distribution of all hibernating bats in North America. We assumed that all intersection localities would negatively affect local bat populations and reassessed their conservation status based on their potential population decline. Our results suggest that WNS will not spread widely throughout North America, being mostly restricted to the east and southeast regions. In contrast, our most pessimistic scenario of population decline indicated that the disease would threaten 32% of the bat species. Our results could help further conservation plans to preserve bat diversity in North America.

Multifunctional High Drug Loading Nanocarriers for Cancer Drug Delivery

NASA Astrophysics Data System (ADS)

Jin, Erlei

2011-12-01

Most anticancer drugs have poor water-solubility, rapid blood clearance, low tumor-selectivity and severe systemic toxicity to healthy tissues. Thus, polymeric nanocarriers have been widely explored for anticancer drugs to solve these problems. However, polymer nanocarriers developed to date still suffer drawbacks including low drug loading contents, premature drug release, slow cellular internalization, slow intracellular drug release and thereby low therapeutic efficiency in cancer thermotherapy. Accordingly, in this dissertation, functional nanocapsules and nanoparticles including high drug loading liposome-like nanocapsules, high drug loading phospholipid-mimic nanocapsules with fast intracellular drug release, high drug loading charge-reversal nanocapsules, TAT based long blood circulation nanoparticles and charge-reversal nuclear targeted nanoparticles are designed and synthesized. These functional carriers have advantages such as high drug loading contents without premature drug release, fast cellular internalization and intracellular drug release, nuclear targeted delivery and long blood circulation. As a result, all these drug carriers show much higher in vitro and in vivo anti-cancer activities.

Advances in Electronic-Nose Technologies for the Detection of Volatile Biomarker Metabolites in the Human Breath

PubMed Central

Wilson, Alphus D.

2015-01-01

Recent advancements in the use of electronic-nose (e-nose) devices to analyze human breath profiles for the presence of specific volatile metabolites, known as biomarkers or chemical bio-indicators of specific human diseases, metabolic disorders and the overall health status of individuals, are providing the potential for new noninvasive tools and techniques useful to point-of-care clinical disease diagnoses. This exciting new area of electronic disease detection and diagnosis promises to yield much faster and earlier detection of human diseases and disorders, allowing earlier, more effective treatments, resulting in more rapid patient recovery from various afflictions. E-nose devices are particularly suited for the field of disease diagnostics, because they are sensitive to a wide range of volatile organic compounds (VOCs) and can effectively distinguish between different complex gaseous mixtures via analysis of electronic aroma sensor-array output profiles of volatile metabolites present in the human breath. This review provides a summary of some recent developments of electronic-nose technologies, particularly involving breath analysis, with the potential for providing many new diagnostic applications for the detection of specific human diseases associated with different organs in the body, detectable from e-nose analyses of aberrant disease-associated VOCs present in air expired from the lungs. PMID:25738426

Ion nose spectral structures observed by the Van Allen Probes

NASA Astrophysics Data System (ADS)

Ferradas, C. P.; Zhang, J.-C.; Spence, H. E.; Kistler, L. M.; Larsen, B. A.; Reeves, G.; Skoug, R.; Funsten, H.

2016-12-01

We present a statistical study of nose-like structures observed in energetic hydrogen, helium, and oxygen ions near the inner edge of the plasma sheet. Nose structures are spectral features named after the characteristic shapes of energy bands or gaps in the energy-time spectrograms of in situ measured ion fluxes. Using 22 months of observations from the Helium Oxygen Proton Electron instrument onboard Van Allen Probe A, we determine the number of noses observed, and the minimum L shell reached and energy of each nose on each pass through the inner magnetosphere. We find that multiple noses occur more frequently in heavy ions than in H+ and are most often observed during quiet times. The heavy-ion noses penetrate to lower L shells than H+ noses, and there is an energy-magnetic local time (MLT) dependence in the nose locations and energies that is similar for all species. The observations are interpreted by using a steady state model of ion drift in the inner magnetosphere. The model is able to explain the energy and MLT dependence of the different types of nose structures. Different ion charge-exchange lifetimes are the main cause for the deeper penetration of heavy-ion noses. The species dependence and preferred geomagnetic conditions of multiple-nose events indicate that they must be on long drift paths, leading to strong charge-exchange effects. The results provide important insight into the spatial distribution, species dependence, and geomagnetic conditions under which nose structures occur.

Estimation of absorbed fraction to the anterior nose from inhaled beta emitters

NASA Astrophysics Data System (ADS)

Moussa, Hanna Moussa

2000-08-01

The main purpose of this research is to introduce a new and more realistic geometry for the anterior nose region (ET1) as an alternative to the one provided in ICRP Publication 66. For a more accurate estimation of electron absorbed fraction (AF) to the nuclei of basal cells in the ET 1 region, the proposed new geometry (frustum of a cone) replaces the cylinder geometry, which was used in ICRP 66. Since the electron absorbed fraction (AF) data in ICRP 66 are calculated based on the nose size for an adult Caucasian male, a second purpose of this research is to investigate how the nose size (different ethnic groups) and nose tissue composition (male, female and adolescent), affects the electron absorbed fraction values. The third aim of this research is to develop a Monte Carlo program to estimate the electron energies that emerge from the surface of spherical dust particles. Given that electrons can be located anywhere between the center and the surface of the sphere, we vary the sphere radius from 0.5 to 50 μm and investigate the effects of self-absorption on the emitted electron energies and absorbed fraction.

21 CFR 868.6225 - Nose clip.

Code of Federal Regulations, 2010 CFR

2010-04-01

... ANESTHESIOLOGY DEVICES Miscellaneous § 868.6225 Nose clip. (a) Identification. A nose clip is a device intended to close a patient's external nares (nostrils) during diagnostic or therapeutic procedures. (b... from the current good manufacturing practice requirements of the quality system regulation in part 820...

Advances in electronic-nose technologies for the detection of volatile biomarker metabolites in the human breath

Treesearch

Alphus D. Wilson

2015-01-01

Recent advancements in the use of electronic-nose (e-nose) devices to analyze human breath profiles for the presence of specific volatile metabolites, known as biomarkers or chemical bio-indicators of specific human diseases, metabolic disorders and the overall health status of individuals, are providing the potential for new noninvasive tools and techniques useful to...

Implications of formulation design on lipid-based nanostructured carrier system for drug delivery to brain.

PubMed

Salunkhe, Sachin S; Bhatia, Neela M; Bhatia, Manish S

2016-05-01

The aim of present investigation was to formulate and develop lipid-based nanostructured carriers (NLCs) containing Idebenone (IDE) for delivery to brain. Attempts have been made to evaluate IDE NLCs for its pharmacokinetic and pharmacodynamic profile through the objective of enhancement in bioavailability and effectivity of drug. Nanoprecipitation technique was used for development of drug loaded NLCs. The components solid lipid Precirol ATO 5, oil Miglyol 840, surfactants Tween 80 and Labrasol have been screened out for formulation development by consideration of preformulation parameters including solubility, Required Hydrophilic lipophilic balance (HLB) of lipids and stability study. Developed IDE NLCs were subjected for particle size, zeta potential, entrapment efficiency (%EE), crystallographic investigation, transmission electron microscopy, in vitro drug release, pharmacokinetics, in vivo and stability study. Formulation under investigation has particle size 174.1 ± 2.6 nm, zeta potential -18.65 ± 1.13 mV and% EE 90.68 ± 2.90. Crystallographic studies exemplified for partial amorphization of IDE by molecularly dispersion within lipid crust. IDE NLCs showed drug release 93.56 ± 0.39% at end of 24 h by following Higuchi model which necessitates for appropriate drug delivery with enhancement in bioavailability of drug by 4.6-fold in plasma and 2.8-fold in brain over plain drug loaded aqueous dispersions. In vivo studies revealed that effect of drug was enhanced by prepared lipid nanocarriers. IDE lipid-based nanostructured carriers could have potential for efficient drug delivery to brain with enhancement in bioavailability of drug over the conventional formulations.

Electronic Nose and Electronic Tongue

NASA Astrophysics Data System (ADS)

Bhattacharyya, Nabarun; Bandhopadhyay, Rajib

Human beings have five senses, namely, vision, hearing, touch, smell and taste. The sensors for vision, hearing and touch have been developed for several years. The need for sensors capable of mimicking the senses of smell and taste have been felt only recently in food industry, environmental monitoring and several industrial applications. In the ever-widening horizon of frontier research in the field of electronics and advanced computing, emergence of electronic nose (E-Nose) and electronic tongue (E-Tongue) have been drawing attention of scientists and technologists for more than a decade. By intelligent integration of multitudes of technologies like chemometrics, microelectronics and advanced soft computing, human olfaction has been successfully mimicked by such new techniques called machine olfaction (Pearce et al. 2002). But the very essence of such research and development efforts has centered on development of customized electronic nose and electronic tongue solutions specific to individual applications. In fact, research trends as of date clearly points to the fact that a machine olfaction system as versatile, universal and broadband as human nose and human tongue may not be feasible in the decades to come. But application specific solutions may definitely be demonstrated and commercialized by modulation in sensor design and fine-tuning the soft computing solutions. This chapter deals with theory, developments of E-Nose and E-Tongue technology and their applications. Also a succinct account of future trends of R&D efforts in this field with an objective of establishing co-relation between machine olfaction and human perception has been included.

Near-infrared optical imaging of nucleic acid nanocarriers in vivo.

PubMed

Rome, Claire; Gravier, Julien; Morille, Marie; Divita, Gilles; Bolcato-Bellemin, Anne-Laure; Josserand, Véronique; Coll, Jean-Luc

2013-01-01

Noninvasive, real-time optical imaging methods are well suited to follow the in vivo distribution of nucleic acid nanocarriers, their dissociation, and the resulting gene expression or inhibition. Indeed, most small animal imaging devices perform bioluminescence and fluorescence measurements without moving the animal, allowing a simple, rapid, and cost-effective method of investigation of several parameters at a time, in longitudinal experiments that can last for days or weeks.Here we help the reader in choosing adapted near-infrared (NIR) fluorophores or pairs of fluorophores for Förster resonance energy transfer assays, imaging of reporter genes, as well as nanocarriers for in vivo gene and siRNA delivery. In addition, we present the labeling methods of these macromolecules and of their payload and the protocols to detect them using bioluminescence and NIR fluorescence imaging in mice.

Transformable DNA Nanocarriers for Plasma Membrane Targeted Delivery of Cytokine

PubMed Central

Sun, Wujin; Ji, Wenyan; Hu, Quanyin; Yu, Jicheng; Wang, Chao; Qian, Chenggen; Hochu, Gabrielle; Gu, Zhen

2016-01-01

Direct delivery of cytokines using nanocarriers holds great promise for cancer therapy. However, the nanometric scale of the vehicles made them susceptible to size-dependent endocytosis, reducing the plasma membrane-associated apoptosis signalling. Herein, we report a tumor microenvironment-responsive and transformable nanocarrier for cell membrane targeted delivery of cytokine. This formulation is comprised of a phospholipase A2 (PLA2) degradable liposome as a shell, and complementary DNA nanostructures (designated as nanoclews) decorated with cytokines as the cores. Utilizing the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as a model cytokine, we demonstrate that the TRAIL loaded DNA nanoclews are capable of transforming into nanofibers after PLA2 activation. The nanofibers with micro-scaled lengths efficiently present the loaded TRAIL to death receptors on the cancer cell membrane and amplified the apoptotic signalling with reduced TRAIL internalization. PMID:27131597

Near-infrared optical imaging of nucleic acid nanocarriers in vivo

PubMed Central

Rome, Claire; Gravier, Julien; Morille, Marie; Divita, Gilles; Bolcato-Bellemin, Anne-Laure; Josserand, Véronique; Coll, Jean-Luc

2013-01-01

Summary Non-invasive, real time optical imaging methods are particularly well suited for the in vivo follow up of the distribution of nucleic acids nanocarriers, their dissociation and finally the resulting gene expression or inhibition. Indeed, most small animal imaging devices are performing bioluminescence and fluorescence measurements without moving the animal, allowing a simple, rapid and cost effective method of investigation of several parameters at a time, in longitudinal experiments that can last for days or weeks. Here we propose to help the reader choosing adapted near-infrared (NIR) fluorophores or pairs of fluorophores for FRET assays, reporter genes as well as nanocarriers for in vivo gene and siRNA delivery. In addition, we present the labeling methods of these macromolecules, and of their payload and the protocols to detect them using bioluminescence and NIR fluorescence imaging in mice. PMID:23070763

Broken Nose

MedlinePlus

... include contact sports, physical fights, falls and motor vehicle accidents that result in facial trauma. A broken ... such as football or hockey Physical altercations Motor vehicle accidents Falls A broken nose can even be ...

Nose profile morphology and accuracy study of nose profile estimation method in Scottish subadult and Indonesian adult populations.

PubMed

Sarilita, Erli; Rynn, Christopher; Mossey, Peter A; Black, Sue; Oscandar, Fahmi

2018-05-01

This study investigated nose profile morphology and its relationship to the skull in Scottish subadult and Indonesian adult populations, with the aim of improving the accuracy of forensic craniofacial reconstruction. Samples of 86 lateral head cephalograms from Dundee Dental School (mean age, 11.8 years) and 335 lateral head cephalograms from the Universitas Padjadjaran Dental Hospital, Bandung, Indonesia (mean age 24.2 years), were measured. The method of nose profile estimation based on skull morphology previously proposed by Rynn and colleagues in 2010 (FSMP 6:20-34) was tested in this study. Following this method, three nasal aperture-related craniometrics and six nose profile dimensions were measured from the cephalograms. To assess the accuracy of the method, six nose profile dimensions were estimated from the three craniometric parameters using the published method and then compared to the actual nose profile dimensions.In the Scottish subadult population, no sexual dimorphism was evident in the measured dimensions. In contrast, sexual dimorphism of the Indonesian adult population was evident in all craniometric and nose profile dimensions; notably, males exhibited statistically significant larger values than females. The published method by Rynn and colleagues (FSMP 6:20-34, 2010) performed better in the Scottish subadult population (mean difference of maximum, 2.35 mm) compared to the Indonesian adult population (mean difference of maximum, 5.42 mm in males and 4.89 mm in females).In addition, regression formulae were derived to estimate nose profile dimensions based on the craniometric measurements for the Indonesian adult population. The published method is not sufficiently accurate for use on the Indonesian population, so the derived method should be used. The accuracy of the published method by Rynn and colleagues (FSMP 6:20-34, 2010) was sufficiently reliable to be applied in Scottish subadult population.

Bioconjugation of recombinant tissue plasminogen activator to magnetic nanocarriers for targeted thrombolysis

PubMed Central

Yang, Hung-Wei; Hua, Mu-Yi; Lin, Kun-Ju; Wey, Shiaw-Pyng; Tsai, Rung-Ywan; Wu, Siao-Yun; Lu, Yi-Ching; Liu, Hao-Li; Wu, Tony; Ma, Yunn-Hwa

2012-01-01

Low-toxicity magnetic nanocarriers (MNCs) composed of a shell of poly [aniline-co-N-(1-one-butyric acid) aniline] over a Fe3O4 magnetic nanoparticle core were developed to carry recombinant tissue plasminogen activator (rtPA) in MNC-rtPA for targeted thrombolysis. With an average diameter of 14.8 nm, the MNCs exerted superparamagnetic properties. Up to 276 μg of active rtPA was immobilized per mg of MNCs, and the stability of the immobilized rtPA was greatly improved during storage at 4°C and 25°C. In vitro thrombolysis testing with a tubing system demonstrated that magnet-guided MNC-rtPA showed significantly improved thrombolysis compared with free rtPA and reduced the clot lysis time from 39.2 ± 3.2 minutes to 10.8 ± 4.2 minutes. In addition, magnet-guided MNC-rtPA at 20% of the regular rtPA dose restored blood flow within 15–25 minutes of treatment in a rat embolism model without triggering hematological toxicity. In conclusion, this improved system is based on magnetic targeting accelerated thrombolysis and is potentially amenable to therapeutic applications in thromboembolic diseases. PMID:23055728

Ion nose spectral structures observed by the Van Allen Probes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ferradas, C. P.; Zhang, J. -C.; Spence, H. E.

Here, we present a statistical study of nose-like structures observed in energetic hydrogen, helium, and oxygen ions near the inner edge of the plasma sheet. Nose structures are spectral features named after the characteristic shapes of energy bands or gaps in the energy-time spectrograms of in situ measured ion fluxes. Using 22 months of observations from the Helium Oxygen Proton Electron (HOPE) instrument onboard Van Allen Probe A, we determine the number of noses observed, and the minimum L-shell reached and energy of each nose on each pass through the inner magnetosphere. We find that multiple noses occur more frequentlymore » in heavy ions than in H +, and are most often observed during quiet times. The heavy-ion noses penetrate to lower L shells than H + noses and there is an energy-magnetic local time (MLT) dependence in the nose locations and energies that is similar for all species. The observations are interpreted using a steady-state model of ion drift in the inner magnetosphere. The model is able to explain the energy and MLT dependence of the different types of nose structures. Different ion charge exchange lifetimes are the main cause for the deeper penetration of heavy-ion noses. The species dependence and preferred geomagnetic conditions of multiple-nose events indicate that they must be on long drift paths, leading to strong charge-exchange effects. The results provide important insight into the spatial distribution, species dependence, and geomagnetic conditions under which nose structures occur.« less

Ion nose spectral structures observed by the Van Allen Probes

DOE PAGES

Ferradas, C. P.; Zhang, J. -C.; Spence, H. E.; ...

2016-11-22

Here, we present a statistical study of nose-like structures observed in energetic hydrogen, helium, and oxygen ions near the inner edge of the plasma sheet. Nose structures are spectral features named after the characteristic shapes of energy bands or gaps in the energy-time spectrograms of in situ measured ion fluxes. Using 22 months of observations from the Helium Oxygen Proton Electron (HOPE) instrument onboard Van Allen Probe A, we determine the number of noses observed, and the minimum L-shell reached and energy of each nose on each pass through the inner magnetosphere. We find that multiple noses occur more frequentlymore » in heavy ions than in H +, and are most often observed during quiet times. The heavy-ion noses penetrate to lower L shells than H + noses and there is an energy-magnetic local time (MLT) dependence in the nose locations and energies that is similar for all species. The observations are interpreted using a steady-state model of ion drift in the inner magnetosphere. The model is able to explain the energy and MLT dependence of the different types of nose structures. Different ion charge exchange lifetimes are the main cause for the deeper penetration of heavy-ion noses. The species dependence and preferred geomagnetic conditions of multiple-nose events indicate that they must be on long drift paths, leading to strong charge-exchange effects. The results provide important insight into the spatial distribution, species dependence, and geomagnetic conditions under which nose structures occur.« less

Asymmetrically pressing nasal splint for crooked nose deformity.

PubMed

Tugrul, Selahattin; Dogan, Remzi; Kocak, Ilker; Ozturan, Orhan

2015-01-01

Correcting crooked nose deformity is one of the most difficult procedure in rhinoplastic surgery. For that reason, the authors have been designed an asymmetrically pressing nasal splint. In this prospective study, the aim was to compare the effects of applying asymmetrically pressing nasal splint and normal symmetrically splint on the crooked nose. This study included 129 patients who were operated on for crooked nose deformity. Patients were divided into 2 groups. Normal symmetrically pressing nasal splint was applied to groups 1a (I type) and 1b (C type). Asymmetrically pressing nasal splint was applied to groups 2a (I type) and 2b (C type). All groups were compared according to deflection angle from the midline, the percentage of postoperative improvement, patient satisfaction with visual analog scale, and complication rate. I-type noses in both groups at postoperative angle values were reduced, and C-type noses in both groups at postoperative angle values were increased significantly compared with preoperative values. I-type noses of group 2 at postoperative angle values compared with group 1 were reduced, and C-type noses were increased in group 2 significantly. Patient satisfaction rate in group 2 were significantly better than in group 1. The closeness ratios to the ideal angles in group 1 were in "good" and "moderate" levels, whereas in group 2, it was in "excellent" level. There was no significant difference in complication rate in both groups. Asymmetrically pressing splint (novel design) showed increasing success rate clearly in crooked nose surgery than in normal splints.

Recent insights in the use of nanocarriers for the oral delivery of bioactive proteins and peptides.

PubMed

Batista, Patrícia; Castro, Pedro M; Madureira, Ana Raquel; Sarmento, Bruno; Pintado, Manuela

2018-03-01

Bioactive proteins and peptides have been used with either prophylactic or therapeutic purposes, presenting inherent advantages as high specificity and biocompatibility. Nanocarriers play an important role in the stabilization of proteins and peptides, offering enhanced buccal permeation and protection while crossing the gastrointestinal tract. Moreover, preparation of nanoparticles as oral delivery systems for proteins/peptides may include tailored formulation along with functionalization aiming bioavailability enhancement of carried proteins or peptides. Oral delivery systems, namely buccal delivery systems, represent an interesting alternative route to parenteric delivery systems to carry proteins and peptides, resulting in higher comfort of administration and, therefore, compliance to treatment. This paper outlines an extensive overview of the existing publications on proteins/peptides oral nanocarriers delivery systems, with special focus on buccal route. Manufacturing aspects of most commonly used nanoparticles for oral delivery (e.g. polymeric nanoparticles using synthetic or natural polymers and lipid nanoparticles) advantages and limitations and potential applications of nanoparticles as proteins/peptides delivery systems will also be thoroughly addressed. Copyright © 2018 Elsevier Inc. All rights reserved.

Merging high doxorubicin loading with pronounced magnetic response and bio-repellent properties in hybrid drug nanocarriers.

PubMed

Bakandritsos, Aristides; Papagiannopoulos, Aristeidis; Anagnostou, Eleni N; Avgoustakis, Konstantinos; Zboril, Radek; Pispas, Stergios; Tucek, Jiri; Ryukhtin, Vasyl; Bouropoulos, Nikolaos; Kolokithas-Ntoukas, Argiris; Steriotis, Theodore A; Keiderling, Uwe; Winnefeld, Frank

2012-08-06

Hybrid magnetic drug nanocarriers are prepared via a self-assembly process of poly(methacrylic acid)-graft-poly(ethyleneglycol methacrylate) (p(MAA-g-EGMA)) on growing iron oxide nanocrystallites. The nanocarriers successfully merge together bio-repellent properties, pronounced magnetic response, and high loading capacity for the potent anticancer drug doxorubicin (adriamicin), in a manner not observed before in such hybrid colloids. High magnetic responses are accomplished by engineering the size of the magnetic nanocrystallites (∼13.5 nm) following an aqueous single-ferrous precursor route, and through adjustment of the number of cores in each colloidal assembly. Complementing conventional magnetometry, the magnetic response of the nanocarriers is evaluated by magnetophoretic experiments providing insight into their internal organization and on their response to magnetic manipulation. The structural organization of the graft-copolymer, locked on the surface of the nanocrystallites, is further probed by small-angle neutron scattering on single-core colloids. Analysis showed that the MAA segments selectively populate the area around the magnetic nanocrystallites, while the poly(ethylene glycol)-grafted chains are arranged as protrusions, pointing towards the aqueous environment. These nanocarriers are screened at various pHs and in highly salted media by light scattering and electrokinetic measurements. According to the results, their stability is dramatically enhanced, as compared to uncoated nanocrystallites, owing to the presence of the external protective PEG canopy. The nanocarriers are also endowed with bio-repellent properties, as evidenced by stability assays using human blood plasma as the medium. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Close-To-Practice Assessment Of Meat Freshness With Metal Oxide Sensor Microarray Electronic Nose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Musatov, V. Yu.; Sysoev, V. V.; Sommer, M.

In this report we estimate the ability of KAMINA e-nose, based on a metal oxide sensor (MOS) microarray and Linear Discriminant Analysis (LDA) pattern recognition, to evaluate meat freshness. The received results show that, 1) one or two exposures of standard meat samples to the e-nose are enough for the instrument to recognize the fresh meat prepared by the same supplier with 100% probability; 2) the meat samples of two kinds, stored at 4 deg. C and 25 deg. C, are mutually recognized at early stages of decay with the help of the LDA model built independently under the e-nosemore » training to each kind of meat; 3) the 3-4 training cycles of exposure to meat from different suppliers are necessary for the e-nose to build a reliable LDA model accounting for the supplier factor. This study approves that the MOS e-nose is ready to be currently utilised in food industry for evaluation of product freshness. The e-nose performance is characterized by low training cost, a confident recognition power of various product decay conditions and easy adjustment to changing conditions.« less

Nanomedicine as a potential approach to empower the new strategies for the treatment of preeclampsia.

PubMed

Valero, Lucie; Alhareth, Khair; Gil, Sophie; Lecarpentier, Edouard; Tsatsaris, Vassilis; Mignet, Nathalie; Fournier, Thierry; Andrieux, Karine

2018-01-31

Preeclampsia is a serious pregnancy disorder characterized by the onset of high blood pressure and proteinuria. Although the understanding of the disease is increasing, it remains without treatment, other than the delivery of the baby and the placenta. This review sets out to discuss some new developments and strategies in the treatment of preeclampsia. We briefly review the current knowledge on the preeclamptic pathophysiology. We then examine the recent trends in preeclampsia treatment and, in particular, the tracks of potential therapeutic targets. Finally, we focus on the possibilities nanocarriers could offer in the management of preeclampsia. Indeed, nanocarriers could help to prevent transplacental passage and promote placental-specific drug delivery, thereby enhancing efficacy and improving safety. Tendencies are then drawn from the available studies on the optimal characteristics of a nanocarrier to deliver drugs to the placenta. Copyright © 2018 Elsevier Ltd. All rights reserved.

Potential of BLM lands in western Fresno and eastern San Benito and Monterey Counties, California, as critical habitats for the endangered San Joaquin kit fox, Vulpes macrotis mutica, and blunt-nosed leopard lizard, Crotaphytus silus

DOE Office of Scientific and Technical Information (OSTI.GOV)

O'Farrell, T.P.; McCue, P.; Kato, T.

1981-11-01

The major objectives were to determine the presence and relative density of the San Joaquin kit fox and blunt-nosed leopard lizard on BLM lands in western Fresno and eastern San Benito and Monterey counties, California, and to determine the potential of these lands as critical habitat for these endangered species. A total of 6220 acres in the Ciervo Hills and 4000 acres near Coalinga were surveyed for both San Joaquin kit fox and blunt-nosed leopard lizards; 810 acres in the Griswold Hills were surveyed for kit fox only; and 2000 acres in the Tumey Hills were surveyed for blunt-nosed leopardmore » lizards only. Eight line transects per mile were used to gather information on: (1) kit fox dens, scats, tracks, and remains of their prey; (2) presence of blunt-nosed leopard lizards; (3) vegetation associations; (4) density of rodent burrows on lands surveyed for leopard lizards; (5) topography; (6) evidence of human activities; (7) presence of other wildlife species; and (8) any additional scientific data related to endangered species. Night spotlight surveys were conducted in the Ciervo Hills, Griswold Hills, and on lands adjacent to Coalinga and San Ardo to document presence of kit fox, their potential prey, and other vertebrates. Of BLM land surveyed in 1981, the Coalinga Land Unit had the highest potential as critical habitat for the San Joaquin kit fox, the Ciervo Hills Land Unit was ranked second,and parcels in the Griswold Hills received the lowest score given since inventories were initiated in 1979. Public lands in the Salinas Valley were too steep to serve as habitat for kit fox. Over 70% of the parcels had only fair to no potential as critical habitat for the blunt-nosed leopard lizard. BLM lands near Coalinga and those in the central plateau of the Tumey Hills visually appeared to have some potential as habitat for the species.« less

Protein-Based Multifunctional Nanocarriers for Imaging, Photothermal Therapy, and Anticancer Drug Delivery.

PubMed

Pan, Uday Narayan; Khandelia, Rumi; Sanpui, Pallab; Das, Subhojit; Paul, Anumita; Chattopadhyay, Arun

2017-06-14

We report a simple approach for fabricating plasmonic and magneto-luminescent multifunctional nanocarriers (MFNCs) by assembling gold nanorods, iron oxide nanoparticles, and gold nanoclusters within BSA nanoparticles. The MFNCs showed self-tracking capability through single- and two-photon imaging, and the potential for magnetic targeting in vitro. Appreciable T 2 -relaxivity exhibited by the MFNCs indicated favorable conditions for magnetic resonance imaging. In addition to successful plasmonic-photothermal therapy of cancer cells (HeLa) in vitro, the MFNCs demonstrated efficient loading and delivery of doxorubicin to HeLa cells leading to significant cell death. The present MFNCs with their multimodal imaging and therapeutic capabilities could be eminent candidates for cancer theranostics.

Nanocarriers for nuclear imaging and radiotherapy of cancer.

PubMed

Mitra, Amitava; Nan, Anjan; Line, Bruce R; Ghandehari, Hamidreza

2006-01-01

Several nanoscale carriers (nanoparticles, liposomes, water-soluble polymers, micelles and dendrimers) have been developed for targeted delivery of cancer diagnostic and therapeutic agents. These carriers can selectively target cancer sites and carry large payloads, thereby improving cancer detection and therapy effectiveness. Further, the combination of newer nuclear imaging techniques providing high sensitivity and spatial resolution such as dual modality imaging with positron emission tomography/computed tomography (PET/CT) and use of nanoscale devices to carry diagnostic and therapeutic radionuclides with high target specificity can enable more accurate detection, staging and therapy planning of cancer. The successful clinical applications of radiolabeled monoclonal antibodies for cancer detection and therapy bode well for the future of nanoscale carrier systems in clinical oncology. Several radiolabeled multifunctional nanocarriers have been effective in detecting and treating cancer in animal models. Nonetheless, further preclinical, clinical and long-term toxicity studies will be required to translate this technology to the care of patients with cancer. The objective of this review is to present a brief but comprehensive overview of the various nuclear imaging techniques and the use of nanocarriers to deliver radionuclides for the diagnosis and therapy of cancer.

Classification of human pathogen bacteria for early screening using electronic nose

NASA Astrophysics Data System (ADS)

Zulkifli, Syahida Amani; Mohamad, Che Wan Syarifah Robiah; Abdullah, Abu Hassan

2017-10-01

This paper present human pathogen bacteria for early screening using electronic nose. Electronic nose (E-nose) known as gas sensor array is a device that analyze the odor measurement give the fast response and less time consuming for clinical diagnosis. Many bacterial pathogens could lead to life threatening infections. Accurate and rapid diagnosis is crucial for the successful management of these infections disease. The conventional method need more time to detect the growth of bacterial. Alternatively, the bacteria are Pseudomonas aeruginosa and Shigella cultured on different media agar can be detected and classifies according to the volatile compound in shorter time using electronic nose (E-nose). Then, the data from electronic nose (E-nose) is processed using statistical method which is principal component analysis (PCA). The study shows the capability of electronic nose (E-nose) for early screening for bacterial infection in human stomach.

Future applications of electronic-nose technologies in healthcare and biomedicine

Treesearch

Alphus D. Wilson

2011-01-01

The development and utilization of many new electronic-nose (e-nose) applications in the healthcare and biomedical fields have continued to rapidly accelerate over the past 20 years. Innovative e-nose technologies are providing unique solutions to a diversity of complex problems in biomedicine that are now coming to fruition. A wide range of electronic-nose instrument...

Treatment protocol for "Mestizo nose" with open rhinoplasty.

PubMed

de la Peña-Salcedo, Jose Abel; Soto-Miranda, Miguel Angel; Lopez-Salguero, Jose Fernando

2011-12-01

The aim of this study was to develop an operative sequence to guide plastic surgeons on how to handle the challenges of "Mestizo nose" during rhinoplasty. This type of nose has characteristics quite different from the Caucasian nose. Rhinoplasties on Mestizo nose represent a surgical challenge because of the anatomical characteristics of a weak frame and thick skin. The Hispanic population has grown, and nowadays a large number of patients requesting rhinoplasty within the US belong to this ethnic group. We have developed an operative sequence for the treatment of Mestizo nose. This operative sequence has been tested in 879 rhinoplasties (92.37% females and 7.62% males, aged 15-63 years, mean age = 39 years). All were primary cases. An algorithm on how to approach the different types of Mestizo nose is presented. We had overall good results using our algorithm, with an improvement in the nasal aesthetics of about 54.75%. Complications were postoperative bleeding (1.37%), pain (0.57%), septal hematoma (0.23%), unaesthetic scars (0.34%), and cartilage extrusion (0.11%). Our revision rate was 5%. We present ten complete cases to show our surgical results. This operative sequence has allowed us to get predictable and reliable surgical outcomes when used in Mestizo rhinoplasty operations. We think it can be very useful for every plastic surgeon who performs Mestizo nose rhinoplasty, although not all steps need to be performed in every case.

Drug solubility in lipid nanocarriers: Influence of lipid matrix and available interfacial area.

PubMed

Göke, Katrin; Bunjes, Heike

2017-08-30

Amongst other strategies for the formulation of poorly water-soluble drugs, solubilization of these drugs in lipid-based formulations is a promising option. Most screening methods for the identification of a suitable lipid-based formulation fail to elucidate the role interfacial effects play for drug solubility in disperse systems. In a novel screening approach called passive drug loading, different preformed lipid nanocarrier dispersions are incubated with drug powder. Afterwards, undissolved drug is filtered off and the amount of solubilized drug is determined. The aim of this study was to identify parameters for drug solubility in pure lipids as well as for drug loading to the lipid-water interface of lipid nanoparticles. Using passive loading, the solubility of eight poorly water-soluble drugs in seven lipid nanocarriers varying in particle size or lipid matrix was investigated. Drug solubility in the nanocarriers did not follow any apparent trend and different drugs dissolved best in different carriers. Drugs with a melting point below approximately 150°C displayed distinctly better solubility than higher melting drugs. Additionally, relating the specific lipid nanocarrier surface area to the drug solubility allowed drawing conclusions on the drug localization. Fenofibrate, dibucaine and, less distinctly also clotrimazole, which all melt below 150°C, were predominantly located in the lipid droplet core of the nanoparticles. In contrast, the five remaining drugs (betamethasone valerate, flufenamic acid, itraconazole, ketoconazole, mefenamic acid) were also located at the lipid-water interface to different, but substantial degrees. The ability to account for drug loading to the lipid-water interface is thus a major advantage of passive loading. Copyright © 2017 Elsevier B.V. All rights reserved.

Graphene-Based Chemical Vapor Sensors for Electronic Nose Applications

NASA Astrophysics Data System (ADS)

Nallon, Eric C.

An electronic nose (e-nose) is a biologically inspired device designed to mimic the operation of the olfactory system. The e-nose utilizes a chemical sensor array consisting of broadly responsive vapor sensors, whose combined response produces a unique pattern for a given compound or mixture. The sensor array is inspired by the biological function of the receptor neurons found in the human olfactory system, which are inherently cross-reactive and respond to many different compounds. The use of an e-nose is an attractive approach to predict unknown odors and is used in many fields for quantitative and qualitative analysis. If properly designed, an e-nose has the potential to adapt to new odors it was not originally designed for through laboratory training and algorithm updates. This would eliminate the lengthy and costly R&D costs associated with materiel and product development. Although e-nose technology has been around for over two decades, much research is still being undertaken in order to find new and more diverse types of sensors. Graphene is a single-layer, 2D material comprised of carbon atoms arranged in a hexagonal lattice, with extraordinary electrical, mechanical, thermal and optical properties due to its 2D, sp2-bonded structure. Graphene has much potential as a chemical sensing material due to its 2D structure, which provides a surface entirely exposed to its surrounding environment. In this configuration, every carbon atom in graphene is a surface atom, providing the greatest possible surface area per unit volume, so that electron transport is highly sensitive to adsorbed molecular species. Graphene has gained much attention since its discovery in 2004, but has not been realized in many commercial electronics. It has the potential to be a revolutionary material for use in chemical sensors due to its excellent conductivity, large surface area, low noise, and versatile surface for functionalization. In this work, graphene is incorporated into a

Discovery of unique and ENM— specific pathophysiologic pathways: Comparison of the translocation of inhaled iridium nanoparticles from nasal epithelium versus alveolar epithelium towards the brain of rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kreyling, Wolfgang G., E-mail: kreyling@helmholtz-muenchen.de

The biokinetics of inhaled nanoparticles (NP) is more complex than that of larger particles since NP may NP deposited on the nasal mucosa of the upper respiratory tract (URT) may translocate to the olfactory bulb of the brain and also via the trigeminus (URT neuronal route); and (b) NP deposited in the lower respiratory tract (LRT) may cross the ABB into blood and enter the brain across the blood-brain-barrier (BBB) or take a neuronal route from enervated tracheo-bronchial epithelia via the vagus nerve. Translocation from both - the URT and the LRT - are quantified during the first 24 hmore » after a 1-hour aerosol inhalation of 20 nm-sized, {sup 192}Ir radiolabeled iridium NP by healthy adult rats using differential exposures: (I) nose-only exposure of the entire respiratory tract or (II) intratracheal (IT) inhalation of intubated and ventilated rats, thereby bypassing the URT and extrathoracic nasal passages. After nose-only exposure brain accumulation (BrAcc) is significantly nine-fold higher than after IT inhalation since the former results from both pathways (a + b) while the latter exposure comes only from pathway (b). Interestingly, there are significantly more circulating NP in blood 24 h after nose-only inhalation than after IT inhalation. Distinguishing translocation from URT versus LRT estimated from the differential inhalation exposures, the former is significantly higher (8-fold) than from the LRT. Although the BrAcc fraction is rather low compared to total NP deposition after this short-term exposure, this study proofs that inhaled insoluble NP can accumulate in the brain from both – URT and LRT which may trigger and/or modulate adverse health effects in the central nervous system (CNS) during chronic exposure. - Highlights: • Nanoparticle (NP) translocation from nose versus lungs to brain is differentiated. • Differential exposure of 20 nm radio-NP:nose-only versus intratracheal inhalation • The nose-brain path precedes via nerves, the

Rhinoplasty: The Asymmetric Crooked Nose-An Overview.

PubMed

Kosins, Aaron M; Daniel, Rollin K; Nguyen, Dananh P

2016-08-01

There are three reasons why the asymmetric crooked nose is one of the greatest challenges in rhinoplasty surgery. First, the complexity of the problem is not appreciated by the patient nor understood by the surgeon. Patients often see the obvious deviation of the nose, but not the distinct differences between the right and left sides. Surgeons fail to understand and to emphasize to the patient that each component of the nose is asymmetric. Second, these deformities can be improved, but rarely made flawless. For this reason, patients are told that the result will be all "-er words," better, straighter, cuter, but no "t-words," there is no perfect nor straight. Most surgeons fail to realize that these cases represent asymmetric noses on asymmetric faces with the variable of ipsilateral and contralateral deviations. Third, these cases demand a wide range of sophisticated surgical techniques, some of which have a minimal margin of error. This article offers an in-depth look at analysis, preoperative planning, and surgical techniques available for dealing with the asymmetric crooked nose. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Acoustic rhinometry of the Indian and Anglo-Saxon nose.

PubMed

Gurr, P; Diver, J; Morgan, N; MacGregor, F; Lund, V

1996-09-01

The internal and external geometry of the nose has previously been shown to differ between Anglo-Saxon, Chinese, and Negro noses. It is therefore important to define the normal geometric nasal parameters of a given race, so as to detect the abnormal nose. We present acoustic rhinometric data, with height-adjusted figures, examining the nasal minimum cross-sectional area (MCA), the distance to the nostril from the MCA, and the MCA between 0-6 cm. These data show no significant differences between Indian and Anglo-Saxon noses.

Pedophilic brain potential responses to adult erotic stimuli.

PubMed

Knott, Verner; Impey, Danielle; Fisher, Derek; Delpero, Emily; Fedoroff, Paul

2016-02-01

Cognitive mechanisms associated with the relative lack of sexual interest in adults by pedophiles are poorly understood and may benefit from investigations examining how the brain processes adult erotic stimuli. The current study used event-related brain potentials (ERP) to investigate the time course of the explicit processing of erotic, emotional, and neutral pictures in 22 pedophilic patients and 22 healthy controls. Consistent with previous studies, early latency anterior ERP components were highly selective for erotic pictures. Although the ERPs elicited by emotional stimuli were similar in patients and controls, an early frontal positive (P2) component starting as early as 185 ms was significantly attenuated and slow to onset in pedophilia, and correlated with a clinical measure of cognitive distortions. Failure of rapid attentional capture by erotic stimuli suggests a relative reduction in early processing in pedophilic patients which may be associated with relatively diminished sexual interest in adults. Copyright © 2016. Published by Elsevier B.V.

Preparation of chitosan-based multifunctional nanocarriers overcoming multiple barriers for oral delivery of insulin.

PubMed

Li, Lei; Jiang, Guohua; Yu, Weijiang; Liu, Depeng; Chen, Hua; Liu, Yongkun; Tong, Zaizai; Kong, Xiangdong; Yao, Juming

2017-01-01

To overcome multiple barriers for oral delivery of insulin, the chitosan-based multifunctional nanocarriers modified by L-valine (LV, used as a target ligand to facilitate the absorption of the small intestine) and phenylboronic acid (PBA, used as a glucose-responsive unit) have been designed and evaluated in this study. The resultant nanocarriers exhibited low cytotoxicity against HT-29 cells and excellent stability against protein solution. The insulin release behaviors were evaluated triggered by pH and glucose in vitro. The chemical stability of loaded insulin against digestive enzyme were established in presence of simulated gastric fluid (SGF) containing pepsin and simulated intestinal fluid (SIF) containing pancreatin, respectively. The uptake behavior of HT-29 cells was evaluated by confocal laser scanning microscope. After oral administration to the diabetic rats, an effective hypoglycemic effect was obtained compared with subcutaneous injection of insulin. This work suggests that L-valine modified chitosan-based multifunctional nanocarriers may be a promising drug delivery carrier for oral administration of insulin. Copyright © 2016 Elsevier B.V. All rights reserved.

Magnetic pH-responsive poly(methacrylic acid-co-acrylic acid)-co-polyvinylpyrrolidone magnetic nano-carrier for controlled delivery of fluvastatin.

PubMed

Amoli-Diva, Mitra; Pourghazi, Kamyar; Mashhadizadeh, Mohammad Hossein

2015-02-01

A novel pH-responsive polymer, poly(methacrylic acid-co-acrylic acid)-co-polyvinyl-pyrrolidone (polymeric nano-carrier) was synthesized and used for encapsulation of 3-aminopropyl triethoxysilane modified Fe3O4 nanoparticles to prepare a new magnetic nano-carrier. The loading and release characteristics of both polymeric and magnetic nano-carriers were investigated using fluvastatin as the model drug. The loading behavior of the carriers was studied by varying concentration of fluvastatin in aqueous medium at 25°C and their release was followed spectrophotometrically (at 304 nm) at 37°C in three different solutions (buffered at pH1.2, 5.5 and 7.2) to simulate gastric and intestine medium. The effect of different parameters on the release of fluvastatin such as the amount of methacrylic acid monomer, cross-linker amount, initiator amount, and magnetic nanoparticles content was also studied. Considering the release kinetics and mechanism of the magnetic nanocarrier besides swelling behavior study of the polymeric nano-carrier reveal Fickian pattern and diffusion controlled mechanism for delivery of fluvastatin. Copyright © 2014 Elsevier B.V. All rights reserved.

Transferrin liposomes of docetaxel for brain-targeted cancer applications: formulation and brain theranostics.

PubMed

Sonali; Singh, Rahul Pratap; Singh, Nitesh; Sharma, Gunjan; Vijayakumar, Mahalingam R; Koch, Biplob; Singh, Sanjay; Singh, Usha; Dash, Debabrata; Pandey, Bajarangprasad L; Muthu, Madaswamy S

2016-05-01

Diagnosis and therapy of brain cancer was often limited due to low permeability of delivery materials across the blood-brain barrier (BBB) and their poor penetration into the brain tissue. This study explored the possibility of utilizing theranostic d-alpha-tocopheryl polyethylene glycol 1000 succinate mono-ester (TPGS) liposomes as nanocarriers for minimally invasive brain-targeted imaging and therapy (brain theranostics). The aim of this work was to formulate transferrin conjugated TPGS coated theranostic liposomes, which contain both docetaxel and quantum dots (QDs) for imaging and therapy of brain cancer. The theranostic liposomes with and without transferrin decoration were prepared and characterized for their particle size, polydispersity, morphology, drug encapsulation efficiency, in-vitro release study and brain theranostics. The particle sizes of the non-targeted and targeted theranostic liposomes were found below 200 nm. Nearly, 71% of drug encapsulation efficiency was achieved with liposomes. The drug release from transferrin conjugated theranostic liposomes was sustained for more than 72 h with 70% of drug release. The in-vivo results indicated that transferrin receptor-targeted theranostic liposomes could be a promising carrier for brain theranostics due to nano-sized delivery and its permeability which provided an improved and prolonged brain targeting of docetaxel and QDs in comparison to the non-targeted preparations.

An Evaluation of Electronic Nose for Space Program Applications

NASA Technical Reports Server (NTRS)

Young, Rebecca C.; Linnell, Bruce R.; Buttner, William J.; Mersqhelte, Barry

2003-01-01

The ability to monitor air contaminants in the Shuttle and the International Space Station is important to ensure the health and safety of astronauts. Three specific space applications have been identified that would benefit from a chemical monitor: organic contaminants in crew cabins, propellant contaminants in the airlock, and pre-combustion fire detection. NASA has assessed several commercial and developing electronic noses (e-noses) for these applications. A preliminary series of tests identified those e-noses that exhibited sufficient sensitivity to the vapors of interest. These e-noses were further tested to assess their ability to identify vapors, and in-house software has been developed to enhance identification. This paper describes the tests, the classification ability of selected e-noses, and the software improvements made to meet the requirements for these space program applications.

Solving the Nose-Hoover thermostat for Nuclear Pasta

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perez Garcia, M. Angeles

2006-06-19

At densities just below nuclear saturation density, there may be possible non-uniform spatial configurations of neutron rich matter. In this work we present a calculation using molecular dynamics techniques for a nuclear system interacting via a semiclassical potential depending on both positions and momenta and kept at fixed temperature by using the Nose-Hoover Thermostat.

Novel ZnO hollow-nanocarriers containing paclitaxel targeting folate-receptors in a malignant pH-microenvironment for effective monitoring and promoting breast tumor regression

PubMed Central

Puvvada, Nagaprasad; Rajput, Shashi; Kumar, B.N. Prashanth; Sarkar, Siddik; Konar, Suraj; Brunt, Keith R.; Rao, Raj R.; Mazumdar, Abhijit; Das, Swadesh K.; Basu, Ranadhir; Fisher, Paul B.; Mandal, Mahitosh; Pathak, Amita

2015-01-01

Low pH in the tumor micromilieu is a recognized pathological feature of cancer. This attribute of cancerous cells has been targeted herein for the controlled release of chemotherapeutics at the tumour site, while sparing healthy tissues. To this end, pH-sensitive, hollow ZnO-nanocarriers loaded with paclitaxel were synthesized and their efficacy studied in breast cancer in vitro and in vivo. The nanocarriers were surface functionalized with folate using click-chemistry to improve targeted uptake by the malignant cells that over-express folate-receptors. The nanocarriers released ~75% of the paclitaxel payload within six hours in acidic pH, which was accompanied by switching of fluorescence from blue to green and a 10-fold increase in the fluorescence intensity. The fluorescence-switching phenomenon is due to structural collapse of the nanocarriers in the endolysosome. Energy dispersion X-ray mapping and whole animal fluorescent imaging studies were carried out to show that combined pH and folate-receptor targeting reduces off-target accumulation of the nanocarriers. Further, a dual cell-specific and pH-sensitive nanocarrier greatly improved the efficacy of paclitaxel to regress subcutaneous tumors in vivo. These nanocarriers could improve chemotherapy tolerance and increase anti-tumor efficacy, while also providing a novel diagnostic read-out through fluorescent switching that is proportional to drug release in malignant tissues. PMID:26145450

Novel ZnO hollow-nanocarriers containing paclitaxel targeting folate-receptors in a malignant pH-microenvironment for effective monitoring and promoting breast tumor regression

NASA Astrophysics Data System (ADS)

Puvvada, Nagaprasad; Rajput, Shashi; Kumar, B. N. Prashanth; Sarkar, Siddik; Konar, Suraj; Brunt, Keith R.; Rao, Raj R.; Mazumdar, Abhijit; Das, Swadesh K.; Basu, Ranadhir; Fisher, Paul B.; Mandal, Mahitosh; Pathak, Amita

2015-07-01

Low pH in the tumor micromilieu is a recognized pathological feature of cancer. This attribute of cancerous cells has been targeted herein for the controlled release of chemotherapeutics at the tumour site, while sparing healthy tissues. To this end, pH-sensitive, hollow ZnO-nanocarriers loaded with paclitaxel were synthesized and their efficacy studied in breast cancer in vitro and in vivo. The nanocarriers were surface functionalized with folate using click-chemistry to improve targeted uptake by the malignant cells that over-express folate-receptors. The nanocarriers released ~75% of the paclitaxel payload within six hours in acidic pH, which was accompanied by switching of fluorescence from blue to green and a 10-fold increase in the fluorescence intensity. The fluorescence-switching phenomenon is due to structural collapse of the nanocarriers in the endolysosome. Energy dispersion X-ray mapping and whole animal fluorescent imaging studies were carried out to show that combined pH and folate-receptor targeting reduces off-target accumulation of the nanocarriers. Further, a dual cell-specific and pH-sensitive nanocarrier greatly improved the efficacy of paclitaxel to regress subcutaneous tumors in vivo. These nanocarriers could improve chemotherapy tolerance and increase anti-tumor efficacy, while also providing a novel diagnostic read-out through fluorescent switching that is proportional to drug release in malignant tissues.

The use and reliability of SymNose for quantitative measurement of the nose and lip in unilateral cleft lip and palate patients.

PubMed

Mosmuller, David; Tan, Robin; Mulder, Frans; Bachour, Yara; de Vet, Henrica; Don Griot, Peter

2016-10-01

It is essential to have a reliable assessment method in order to compare the results of cleft lip and palate surgery. In this study the computer-based program SymNose, a method for quantitative assessment of the nose and lip, will be assessed on usability and reliability. The symmetry of the nose and lip was measured twice in 50 six-year-old complete and incomplete unilateral cleft lip and palate patients by four observers. For the frontal view the asymmetry level of the nose and upper lip were evaluated and for the basal view the asymmetry level of the nose and nostrils were evaluated. A mean inter-observer reliability when tracing each image once or twice was 0.70 and 0.75, respectively. Tracing the photographs with 2 observers and 4 observers gave a mean inter-observer score of 0.86 and 0.92, respectively. The mean intra-observer reliability varied between 0.80 and 0.84. SymNose is a practical and reliable tool for the retrospective assessment of large caseloads of 2D photographs of cleft patients for research purposes. Moderate to high single inter-observer reliability was found. For future research with SymNose reliable outcomes can be achieved by using the average outcomes of single tracings of two observers. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

21 CFR 878.3680 - Nose prosthesis.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Nose prosthesis. 878.3680 Section 878.3680 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Prosthetic Devices § 878.3680 Nose prosthesis. (a...

21 CFR 878.3680 - Nose prosthesis.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Nose prosthesis. 878.3680 Section 878.3680 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Prosthetic Devices § 878.3680 Nose prosthesis. (a...

21 CFR 878.3680 - Nose prosthesis.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Nose prosthesis. 878.3680 Section 878.3680 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Prosthetic Devices § 878.3680 Nose prosthesis. (a...

21 CFR 878.3680 - Nose prosthesis.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Nose prosthesis. 878.3680 Section 878.3680 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Prosthetic Devices § 878.3680 Nose prosthesis. (a...

21 CFR 878.3680 - Nose prosthesis.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Nose prosthesis. 878.3680 Section 878.3680 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Prosthetic Devices § 878.3680 Nose prosthesis. (a...

[Surgical anatomy of the nose].

PubMed

Nguyen, P S; Bardot, J; Duron, J B; Jallut, Y; Aiach, G

2014-12-01

Thorough knowledge of the anatomy of the nose is an essential prerequisite for preoperative analysis and the understanding of surgical techniques. Like a tent supported by its frame, the nose is an osteo-chondral structure covered by a peri-chondroperiosteal envelope, muscle and cutaneous covering tissues. For didactic reasons, we have chosen to treat this chapter in the form of comments from eight key configurations that the surgeon should acquire before performing rhinoplasty. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Electronic Nose: A Promising Tool For Early Detection Of Alicyclobacillus spp In Soft Drinks

NASA Astrophysics Data System (ADS)

Concina, I.; Bornšek, M.; Baccelliere, S.; Falasconi, M.; Sberveglieri, G.

2009-05-01

In the present work we investigate the potential use of the Electronic Nose EOS835 (SACMI scarl, Italy) to early detect Alicyclobacillus spp in two flavoured soft drinks. These bacteria have been acknowledged by producer companies as a major quality control target microorganisms because of their ability to survive commercial pasteurization processes and produce taint compounds in final product. Electronic Nose was able to distinguish between uncontaminated and contaminated products before the taint metabolites were identifiable by an untrained panel. Classification tests showed an excellent rate of correct classification for both drinks (from 86% uo to 100%). High performance liquid chromatography analyses showed no presence of the main metabolite at a level of 200 ppb, thus confirming the skill of the Electronic Nose technology in performing an actual early diagnosis of contamination.

Capsid-like supramolecular dendritic systems as pH-responsive nanocarriers for drug penetration and site-specific delivery.

PubMed

Li, Yachao; Lai, Yusi; Xu, Xianghui; Zhang, Xiao; Wu, Yahui; Hu, Cheng; Gu, Zhongwei

2016-02-01

Supramolecular dendritic systems emerge as a promising new-generation bioinspired nanoplatform for nanomedicine. Herein, we report capsid-like mimics self-assembled from peptide dendrimers and functionalized peptides to enhance drug penetration and site-specific delivery for tumor therapy. These drug-loaded supramolecular dendritic systems are endowed with capsid-like component and nanostructure by a facile supramolecular approach. As expected, the drug-loaded capsid-like nanocarriers show some desirable advantages for antitumor drug delivery: a) well-defined nanostructure to improve drug location at tumor site, b) capsid-like architecture to enhance drug penetration, c) high internalization, pH-controlled release and nuclear delivery to jointly achieve site-specific delivery. Based on these merits, the drug-loaded capsid nanocarriers provide efficient tumor suppression to 4T1 tumor bearing BALB/c mice and decrease the DOX-induced toxicity during treatment course. Dendrimers have been tested in many clinical trials as nanocarriers, without great success due to many limitations. Here, the authors attempted to address these issues by developing supramolecular dendritic systems, which mimic capsids in viruses. Both in-vitro and in-vivo studies showed promising results. This work should provide a platform for further development of dendrimer-based nanocarriers for drug delivery. Copyright © 2015 Elsevier Inc. All rights reserved.

Electronic nose for detecting strawberry fruit maturity

USDA-ARS?s Scientific Manuscript database

An electronic nose (e-nose) composed of eighteen different metal oxide gas sensors was used to characterize the volatile patterns of ‘Strawberry Festival’ and ‘Florida Radiance’ strawberry fruit at five developmental stages: white, half red, three-quarter red, full ripe, and overripe. Strawberry sam...

Transdermal Drug Delivery: Opportunities and Challenges for Controlled Delivery of Therapeutic Agents Using Nanocarriers.

PubMed

Kurmi, Balak Das; Tekchandani, Pawan; Paliwal, Rishi; Paliwal, Shivani Rai

2017-01-01

Transdermal drug delivery represents an extremely attractive and innovative route across the skin owing to the possibility for achieving systemic effect of drugs. The present scenario demands a special focus on developing safe medicine with minimized toxic adverse effects related to most of the pharmacologically active agents. Transdermal drug delivery would be a focal paradigm which provides patient convenience, first-pass hepatic metabolism avoidance, local targeting and reduction in toxic effect related to various categories of drugs like, analgesics, antiinflammatory, antibiotics, antiviral, anaesthetic, anticancer etc. Even this route has challenges due to highly organized structure of skin which acts as a main barrier to penetration of drug via the skin. Several alternative possible strategies are available which overcome these barriers, including use of penetration enhancer, eletroporation, iontophoresis and various nanotechnologically developed nanocarrier systems. The latest one includes employing liposome, dendrimers, nanoparticles, ethosome, carbon nanotube and many more to avoid associated limitations of conventional formulations. Numerous transdermal products such as Estrasorb, Diractin, VivaGel®, Daytrana®, Aczone, Sileryst® are available in the market having a novel strategy to achieve higher penetration of drugs. This encourages formulation fraternity to develop structurally deformable and stable nanocarriers as an alternative approach for controlled and reliable drug delivery across the skin barrier. In this review, we will discuss nanocarriers mediated approaches that come-up with the solutions to the different challenges towards transdermal drug delivery, its clinical importance and latest insight to research in it. The reports presented in this review confirm the wide application of nanocarriers for transdermal delivery of drug/gene. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Uncommon foreign body in a nose].

PubMed

Alagić-Smailbegović, Jasminka; Hadzić, Edina; Sutalo, Kamenko; Resić, Mudzahid

2007-01-01

Foreign body in the nose most frequently occurs in childhood. It could be of various origin, pieces of toys, paper and uncommon metal body. Consequences include one- sided nasal breathing problem, nasal secretion and in some cases pain and secretion become purulent. The aim of this paper is to present uncommon foreign body in the nose. RTG diagnosis and extraction are the methods of choice.

Albumin based versatile multifunctional nanocarriers for cancer therapy: Fabrication, surface modification, multimodal therapeutics and imaging approaches.

PubMed

Kudarha, Ritu R; Sawant, Krutika K

2017-12-01

Albumin is a versatile protein used as a carrier system for cancer therapeutics. As a carrier it can provide tumor specificity, reduce drug related toxicity, maintain therapeutic concentration of the active moiety like drug, gene, peptide, protein etc. for long period of time and also reduce drug related toxicities. Apart from cancer therapy, it is also utilized in the imaging and multimodal therapy of cancer. This review highlights the important properties, structure and types of albumin based nanocarriers with regards to their use for cancer targeting. It also provides brief discussion on methods of preparation of these nanocarriers and their surface modification. Applications of albumin nanocarriers for cancer therapy, gene delivery, imaging, phototherapy and multimodal therapy have also been discussed. This review also provides brief discussion about albumin based marketed nano formulations and those under clinical trials. Copyright © 2017 Elsevier B.V. All rights reserved.

Nanocarrier possibilities for functional targeting of bioactive peptides and proteins: state-of-the-art.

PubMed

Moutinho, Carla G; Matos, Carla M; Teixeira, José A; Balcão, Victor M

2012-02-01

This review attempts to provide an updated compilation of studies reported in the literature pertaining to production of nanocarriers encasing peptides and/or proteins, in a way that helps the reader direct a bibliographic search and develop an integrated perspective of the subject. Highlights are given to bioactive proteins and peptides, with a special focus on those from dairy sources (including physicochemical characteristics and properties, and biopharmaceutical application possibilities of e.g. lactoferrin and glycomacropeptide), as well as to nanocarrier functional targeting. Features associated with micro- and (multiple) nanoemulsions, micellar systems, liposomes and solid lipid nanoparticles, together with biopharmaceutical considerations, are presented in the text in a systematic fashion.

Chitosan-Gated Magnetic-Responsive Nanocarrier for Dual-Modal Optical Imaging, Switchable Drug Release, and Synergistic Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Hui; Mu, Qingxin; Revia, Richard

In this study, we present a multifunctional yet structurally simple nanocarrier that has a high drug loading capacity, releases drug in response to onset of an AC magnetic field, and can serve as a long-term imaging contrast agent and effectively kills cancer cells by synergistic action. This nanocarrier (HMMC-NC) has a spherical shell structure with a center cavity of 80 nm in diameter. The shell is comprised of two layers: an inner layer of magnetite that exhibits superparamagnetism and an outer layer of mesoporous carbon embedded with carbon dots that exhibit photoluminescence property. Thus in addition to being a drugmore » carrier, HMMC-NC is also a contrast agent for bioimaging. The switchable drug release is enabled by the chitosan molecules attached on the nanocarrier as the switching material which turns on or off the drug release in response to the application or withdrawal of an AC magnetic field.« less

Delivery system for mefenamic acid based on the nanocarrier layered double hydroxide: Physicochemical characterization and evaluation of anti-inflammatory and antinociceptive potential.

PubMed

Cunha, Vanessa R R; Guilherme, Viviane A; de Paula, Eneida; de Araujo, Daniele R; Silva, Renan O; Medeiros, Jand V R; Leite, José R S A; Petersen, Philippe A D; Foldvari, Marianna; Petrilli, Helena M; Constantino, Vera R L

2016-01-01

The anionic form of the drug mefenamic acid intercalated into the nanocarrier layered double hydroxide (LDH-Mef) was evaluated by anti-inflammatory and antinociceptive assays. The LDH-Mef material was characterized by a set of physicochemical techniques, which was supported by Density Functional Theory calculations. The pharmacological effects of LDH-Mef (40 wt% of drug) were evaluated by hemolytic, anti-inflammatory activity and antinociceptive assays. In vivo assays were conducted for the first time in order to assess the LDH-Mef potential. The hemolytic effects decreased for the intercalated Mef as demonstrated by the higher tolerated hemolytic concentration (1.83 mM) compared to mefenamic acid (MefH), 0.48 mM. Pretreatment of animals with MefH or LDH-Mef reduced carrageenan-, dextran sulfate- and PGE2-induced paw edema. MefH or LDH-Mef also decrease total leucocytes and neutrophil counts of the peritoneal cavity after inflammation induction with carrageenan. In the nociception model, oral pretreatment with LDH-Mef reduced mechanical hypernociception carrageenan-induced after 3-4h and also the number of writhings induced by acetic acid. This work shows the increase of the anti-inflammatory and antinociceptive potential of the drug confined into the LDH, as well as, its hemolytic effect. Copyright © 2015 Elsevier B.V. All rights reserved.

Electronic Noses and Tongues: Applications for the Food and Pharmaceutical Industries

PubMed Central

Baldwin, Elizabeth A.; Bai, Jinhe; Plotto, Anne; Dea, Sharon

2011-01-01

The electronic nose (e-nose) is designed to crudely mimic the mammalian nose in that most contain sensors that non-selectively interact with odor molecules to produce some sort of signal that is then sent to a computer that uses multivariate statistics to determine patterns in the data. This pattern recognition is used to determine that one sample is similar or different from another based on headspace volatiles. There are different types of e-nose sensors including organic polymers, metal oxides, quartz crystal microbalance and even gas-chromatography (GC) or combined with mass spectroscopy (MS) can be used in a non-selective manner using chemical mass or patterns from a short GC column as an e-nose or “Z” nose. The electronic tongue reacts similarly to non-volatile compounds in a liquid. This review will concentrate on applications of e-nose and e-tongue technology for edible products and pharmaceutical uses. PMID:22163873

Applications and advances in electronic-nose technologies

Treesearch

A. D. Wilson; M. Baietto

2009-01-01

Electronic-nose devices have received considerable attention in the field of sensor technology during the past twenty years, largely due to the discovery of numerous applications derived from research in diverse fields of applied sciences. Recent applications of electronic nose technologies have come through advances in sensor design, material improvements, software...

The Use of Nanocarriers in Acute Myeloid Leukaemia Therapy: Challenges and Current Status.

PubMed

Sauvage, Félix; Barratt, Gillian; Herfindal, Lars; Vergnaud-Gauduchon, Juliette

2016-01-01

Chemotherapy for AML is hampered by severe side-effects and failure to eliminate all the blasts that eventually leads to relapse. The use of nanosized particulate drug carriers such as liposomes and polymeric nanoparticles has the potential to improve AML therapy by delivering more of the drug to the disease site, thereby reducing toxicity. For example, encapsulation in liposomes reduces the cardiotoxicity of anthracyclines, giving an improved therapeutic index. Moreover, when the surface properties are engineered appropriately, nanocarriers remain in the circulation and extravasate in tissues with sinusoidal capillaries, one of which is bone marrow, leading to a more favourable distribution of the associated drug. Drug carrier technology contributes to the development of newer drugs, such as nucleic acids that can be protected from degradation and delivered into cells, thus opening the way for gene-silencing strategies. Furthermore, carrier systems provide a means of dispersing poorly water-soluble molecule for in vivo administration and thus increase the "druggability" of new lead compounds, such as heat-shock protein inhibitors. Particulate carriers can transport more than one active agent, allowing synergistic action and theranostic strategies. Notably, phase I and II clinical trials are being performed with CPX-351, a liposomal formulation containing cytarabine and daunorubicin at an optimal ratio. Finally, by attaching suitable ligands to the nanocarrier surface, specific targeting to AML cells can be achieved. In this review, we give examples of successful targeting to folate and transferrin receptors against AML.

Nanocarriers as phototherapeutic drug delivery system: Appraisal of three different nanosystems in an in vivo and in vitro exploratory study.

PubMed

Ricci-Junior, Eduardo; de Oliveira de Siqueira, Luciana Betzler; Rodrigues, Raphaela Aparecida Schuenck; Sancenón, Félix; Martínez-Máñez, Ramón; de Moraes, João Alfredo; Santos-Oliveira, Ralph

2018-03-01

The use of nanosystems as diagnosing and therapy systems is increasing each year. There are several nanosystems available and the most prominent ones are: mesoporous silica, nanoemulsion and polymeric nanoparticles. With characteristics like low toxicology, and easy-producing process they have advantages when compared with the traditional system used, as they show specific targeting, controlled release, and higher penetration. In this study we tested three different nanocarriers (polymeric nanoparticles, nanoemulsion and mesoporous silica) containing phthalocyanineas possible PDT drugs (nanodrugs). They were tested in vitro and in vivo: cells and healthy mice, respectively, in order to understand the biological behavior and reach the initial conclusions. The results in cells showed that a dose response was observed with different concentrations of the three nanocarriers. The results in animal showed that all nanosystems have potential for application in PDT, since they were able to produce a visible effect in healthy animals. Copyright © 2017 Elsevier B.V. All rights reserved.

Transient aero-thermal mapping of passive Thermal Protection system for nose-cap of Reusable Hypersonic Vehicle

NASA Astrophysics Data System (ADS)

Mahulikar, Shripad P.; Khurana, Shashank; Dungarwal, Ritesh; Shevakari, Sushil G.; Subramanian, Jayakumar; Gujarathi, Amit V.

2008-12-01

The temperature field history of passive Thermal Protection System (TPS) material at the nose-cap (forward stagnation region) of a Reusable Hypersonic Vehicle (RHV) is generated. The 3-D unsteady heat transfer model couples conduction in the solid with external convection and radiation that are modeled as time-varying boundary conditions on the surface. Results are presented for the following two cases: (1) nose-cap comprised of ablative TPS material only (SIRCA/PICA), and (2) nose-cap comprised of a combination of ablative TPS material with moderate thermal conductivity and insulative TPS material. Comparison of the temperature fields of SIRCA and PICA [Case (1)] indicates lowering of the peak stagnation region temperatures for PICA, due to its higher thermal conductivity. Also, the use of PICA and insulative TPS [Case (2)] for the nose-cap has higher potential for weight reduction than the use of ablative TPS alone.

Assessment of compost maturity by using an electronic nose.

PubMed

López, Rafael; Giráldez, Inmaculada; Palma, Alberto; Jesús Díaz, M

2016-02-01

The composting process produces and emits hundreds of different gases. Volatile organic compounds (VOCs) can provide information about progress of composting process. This paper is focused on the qualitative and quantitative relationships between compost age, as sign of compost maturity, electronic-nose (e-nose) patterns and composition of compost and composting gas at an industrial scale plant. Gas and compost samples were taken at different depths from composting windrows of different ages. Temperature, classical chemical parameters, O2, CO, combustible gases, VOCs and e-nose profiles were determined and related using principal component analysis (PCA). Factor analysis carried out to a data set including compost physical-chemical properties, pile pore gas composition and composting time led to few factors, each one grouping together standard composting parameters in an easy to understand way. PCA obtained from e-nose profiles allowed the classifying of piles, their aerobic-anaerobic condition, and a rough estimation of the composting time. That would allow for immediate and in-situ assessment of compost quality and maturity by using an on-line e-nose. The e-nose patterns required only 3-4 sensor signals to account for a great percentage (97-98%) of data variance. The achieved patterns both from compost (chemical analysis) and gas (e-nose analysis) samples are robust despite the high variability in feedstock characteristics (3 different materials), composting conditions and long composting time. GC-MS chromatograms supported the patterns. Copyright © 2015 Elsevier Ltd. All rights reserved.

Handbook of Machine Olfaction: Electronic Nose Technology

NASA Astrophysics Data System (ADS)

Pearce, Tim C.; Schiffman, Susan S.; Nagle, H. Troy; Gardner, Julian W.

2003-02-01

"Electronic noses" are instruments which mimic the sense of smell. Consisting of olfactory sensors and a suitable signal processing unit, they are able to detect and distinguish odors precisely and at low cost. This makes them very useful for a remarkable variety of applications in the food and pharmaceutical industry, in environmental control or clinical diagnostics and more. The scope covers biological and technical fundamentals and up-to-date research. Contributions by renowned international scientists as well as application-oriented news from successful "e-nose" manufacturers give a well-rounded account of the topic, and this coverage from R&D to applications makes this book a must-have read for e-nose researchers, designers and users alike.

The air-conditioning capacity of the human nose.

PubMed

Naftali, Sara; Rosenfeld, Moshe; Wolf, Michael; Elad, David

2005-04-01

The nose is the front line defender of the respiratory system. Unsteady simulations in three-dimensional models have been developed to study transport patterns in the human nose and its overall air-conditioning capacity. The results suggested that the healthy nose can efficiently provide about 90% of the heat and the water fluxes required to condition the ambient inspired air to near alveolar conditions in a variety of environmental conditions and independent of variations in internal structural components. The anatomical replica of the human nose showed the best performance and was able to provide 92% of the heating and 96% of the moisture needed to condition the inspired air to alveolar conditions. A detailed analysis explored the relative contribution of endonasal structural components to the air-conditioning process. During a moderate breathing effort, about 11% reduction in the efficacy of nasal air-conditioning capacity was observed.

Development of a macrophage-targeting and phagocytosis-inducing bio-nanocapsule-based nanocarrier for drug delivery.

PubMed

Li, Hao; Tatematsu, Kenji; Somiya, Masaharu; Iijima, Masumi; Kuroda, Shun'ichi

2018-06-01

liposomes. Our results suggested that GL-BNCs and GL-virosomes would serve as promising drug delivery system nanocarriers for targeting delivery to macrophages. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Novel nanocarriers for topical drug delivery: investigating delivery efficiency and distribution in skin using two-photon microscopy

NASA Astrophysics Data System (ADS)

Kirejev, Vladimir; Guldbrand, Stina; Bauer, Brigitte; Smedh, Maria; Ericson, Marica B.

2011-03-01

The complex structure of skin represents an effective barrier against external environmental factors, as for example, different chemical and biochemical compounds, yeast, bacterial and viral infections. However, this impermeability prevents efficient transdermal drug delivery which limits the number of drugs that are able to penetrate the skin efficiently. Current trends in drug application through skin focus on the design and use of nanocarriers for transport of active compounds. The transport systems applied so far have several drawbacks, as they often have low payload, high toxicity, a limited variability of inclusion molecules, or long degradation times. The aim of these current studies is to investigate novel topical drug delivery systems, e.g. nanocarriers based on cyclic oligosaccharides - cyclodextrins (CD) or iron (III)-based metal-organic frameworks (MOF). Earlier studies on cell cultures imply that these drug nanocarriers show promising characteristics compared to other drug delivery systems. In our studies, we use two-photon microscopy to investigate the ability of the nanocarriers to deliver compounds through ex-vivo skin samples. Using near infrared light for excitation in the so called optical window of skin allows deep-tissue visualization of drug distribution and localization. In addition, it is possible to employ two-photon based fluorescence correlation spectroscopy for quantitative analysis of drug distribution and concentrations in different cell layers.

Nose surgery - slideshow

MedlinePlus

... the size and shape of the nose. Review Date 1/10/2017 Updated by: David A. Lickstein, MD, FACS, specializing in cosmetic and reconstructive plastic surgery, Palm Beach Gardens, FL. Review provided by VeriMed Healthcare ...

Probing the intracellular fate of supramolecular nanocarriers and their cargo with FRET schemes

NASA Astrophysics Data System (ADS)

Thapaliya, Ek Raj; Fowley, Colin; Callan, Bridgeen; Tang, Sicheng; Zhang, Yang; Callan, John F.; Raymo, Françisco M.

2017-02-01

We designed a strategy to monitor self-assembling supramolecular nanocarriers and their cargo simultaneously in the intracellular space with fluorescence measurements. It is based on Förster resonance energy transfer (FRET) between complementary chromophores covalently integrated in the macromolecular backbone of amphiphilic polymers and/or noncovalently encapsulated in supramolecular assemblies of the amphiphilic components. Indeed, these polymers assemble into a micelles in aqueous phase to bring energy donors and acceptors in close proximity and allow energy transfer. The resulting supramolecular assemblies maintain their integrity after travelling into the intracellular space and do not lose their molecular guests in the process. Furthermore, this mechanism can also be exploited to probe the fate of complementary nanoparticles introduced within cells in consecutive incubation steps. Efficient energy transfer occurs in the intracellular space after the sequential incubation of nanocarriers incorporating donors first and then nanoparticles containing acceptors or vice versa. The two sets of nanostructured assemblies ultimately co-localize in the cell interior to bring donors and acceptors together and enable energy transfer. Thus, this protocol is particularly valuable to monitor the transport properties of supramolecular nanocarriers inside living cells and can eventually contribute to the fundamental understating of the ability of these promising vehicles to deliver contrast agents and/or drugs intracellularly in view of possible diagnostics and/or therapeutic applications.

Facile fabrication of a near-infrared responsive nanocarrier for spatiotemporally controlled chemo-photothermal synergistic cancer therapy

NASA Astrophysics Data System (ADS)

Wan, Hao; Zhang, Yi; Liu, Zheyi; Xu, Guiju; Huang, Guang; Ji, Yongsheng; Xiong, Zhichao; Zhang, Quanqing; Dong, Jing; Zhang, Weibing; Zou, Hanfa

2014-07-01

Remote-controlled nanocarriers for drug delivery are of great promise to provide timely, sensitive and spatiotemporally selective treatments for cancer therapy. Due to convenient and precise manipulation, deep penetration through tissues and excellent biocompatibility, near-infrared (NIR) irradiation is a preferred external stimulus for triggering the release of loaded drugs. In this work, for spatiotemporally controlled chemo-photothermal synergistic cancer therapy, a NIR responsive nanocarrier was fabricated using reduced graphene oxide nanosheets (rNGO) decorated with mesoporous silica shell and the subsequent functionalization of the thermoresponsive polymer brushes (pNIPAM-co-pAAm) at the outlet of the silica pore channels. rNGO, which combined with the mesoporous silica shell provide a high loading capacity for anticancer drugs (doxorubicin, DOX), was assigned to sense NIR irradiation for the manipulation of pNIPAM-co-pAAm valve to control the diffusion of loaded DOX. Under NIR irradiation, rNGO would generate heat, which could not only elevate the surrounding temperature over the low critical solution temperature (LCST) of pNIPAM-co-pAAm to open the thermoresponsive polymer valve and promote the diffusion of DOX, but also kill the cancer cells through the hypothermia effect. By manipulating NIR irradiation, the nanocarrier exhibited efficiently controlled release of loaded DOX both in the buffer and in living HeLa cells (the model cancer cells), providing powerful and site-targeted treatments, which can be attributed to synergistic effects of chemo-photothermal therapy. To sum up, this novel nanocarrier is an excellent drug delivery platform in remote-controlled chemo-photothermal synergistic cancer therapy via NIR irradiation.Remote-controlled nanocarriers for drug delivery are of great promise to provide timely, sensitive and spatiotemporally selective treatments for cancer therapy. Due to convenient and precise manipulation, deep penetration through

Nose-only exposure system

DOEpatents

Cannon, William C.; Bass, Edward W.; Decker, Jr., John R.

1988-01-01

An exposure system for supplying a gaseous material, i.e. an aerosol, gas or a vapor, directly to the noses of experimental animals includes concentric vertical inner and outer manifolds. The outer manifold connects with the necks of a large number of bottles in which the animals are confined with their noses adjacent the bottle necks. Readily detachable small tubes communicate with the inner manifold and extend to the necks of the bottles. The upper end of the outer manifold and the lower end of the inner manifold are closed. Gaseous material is supplied to the upper end of the inner manifold, flows through the small tubes to points adjacent the noses of the individual animals, then is drawn out through the bottom of the outer manifold. The bottles are readily removable and the device can be disassembled, e.g., for cleaning, by removing the bottles, removing the small tubes, and lifting the inner manifold from the outer manifold. The bottles are supported by engagement of their necks with the outer manifold supplemented, if additional support is required, by individual wire cradles. The outer ends of the bottles are closed by plugs, through which pass metal tubes which receive the tails of the animals (usually rodents) and which serve to dissipate body heat. The entire device is mounted for rotation on turntable bearings.

Identification of sulfur fumed Pinelliae Rhizoma using an electronic nose

PubMed Central

Zhou, Xia; Wan, Jun; Chu, Liang; Liu, Wengang; Jing, Yafeng; Wu, Chunjie

2014-01-01

Background: Pinelliae Rhizoma is a commonly used Chinese herb which will change brown during the natural drying process. However, sulfur fumed Pinelliae Rhizoma will get a better appearance than naturally dried one. Sulfur fumed Pinelliae Rhizoma is potentially toxical due to sulfur dioxide and sulfites formed during the fuming procedures. The odor components in sulfur fumed Pinelliae Rhizoma is complex. At present, there is no analytical method available to determine sulfur fumed Pinelliae Rhizoma simply and rapidly. To ensure medication safety, it is highly desirable to have an effective and simple method to identify sulfur fumed Pinelliae Rhizoma. Materials and Methods: This paper presents a novel approach using an electronic nose based on metal oxide sensors to identify whether Pinelliae Rhizoma was fumed with sulfur, and to predict the fuming degree of Pinelliae Rhizoma. Multivariate statistical methods such as principal components analysis (PCA), discriminant factorial analysis (DFA) and partial least squares (PLS) were used for data analyzing and identification. The use of the electronic nose to discriminate between different fuming degrees Pinelliae Rhizoma and naturally dried Pinelliae Rhizoma was demonstrated. Results: The electronic nose was also successfully applied to identify unknown samples including sulfur fumed samples and naturally dried samples, high recognition value was obtained. Quantitative analysis of fuming degree of Pinelliae Rhizoma was also demonstrated. The method developed is simple and fast, which provides a new quality control method of Chinese herbs from the aspect of odor. Conclusion: It has shown that this electronic nose based metal oxide sensor is sensitive to sulfur and sulfides. We suggest that it can serve as a supportive method to detect residual sulfur and sulfides. PMID:24914293

Evaluation of boron nitride nanotubes and hexagonal boron nitrides as nanocarriers for cancer drugs.

PubMed

Emanet, Melis; Şen, Özlem; Çulha, Mustafa

2017-04-01

Boron nitride nanotubes (BNNTs) and hexagonal boron nitrides (hBNs) are novel nanostructures with high mechanical strengths, large surface areas and excellent biocompatibilities. Here, the potential use of BNNTs and hBNs as nanocarriers was comparatively investigated for use with cancer drugs. Doxorubicin (Dox) and folate are used as model drugs and targeting agents, respectively. The obtained results indicate that BNNTs have about a threefold higher Dox loading capacity than hBNs. It was also found that cellular uptake of folate-Dox-BNNTs was much higher when compared with Dox-BNNTs for HeLa cells, due to the presence of folate receptors on the cell surface, leading to increased cancer cell death. In summary, folate and Dox conjugated BNNTs are promising agents in nanomedicine and may have potential drug delivery applications.

Northrop F-5F shark nose development

NASA Technical Reports Server (NTRS)

Edwards, O. R.

1978-01-01

During spin susceptibility testing of the Northrop F-5F airplane, two erect spin entries were obtained from purely longitudinal control inputs at low speed. Post flight analysis of the data showed that the initial yaw departure occurred at zero sideslip, and review of wind tunnel data showed significant yawing moments present at angles of attack well above stall. Further analysis of this wind tunnel data indicated that the yawing moments were being generated by the long slender nose of the airplane. Redesign of the nose was accomplished, resulting in a nose configuration which completely alleviated the asymmetric yawing moments.

Ethosomal nanocarriers: the impact of constituents and formulation techniques on ethosomal properties, in vivo studies, and clinical trials.

PubMed

Abdulbaqi, Ibrahim M; Darwis, Yusrida; Khan, Nurzalina Abdul Karim; Assi, Reem Abou; Khan, Arshad A

2016-01-01

Ethosomal systems are novel lipid vesicular carriers containing a relatively high percentage of ethanol. These nanocarriers are especially designed for the efficient delivery of therapeutic agents with different physicochemical properties into deep skin layers and across the skin. Ethosomes have undergone extensive research since they were invented in 1996; new compounds were added to their initial formula, which led to the production of new types of ethosomal systems. Different preparation techniques are used in the preparation of these novel carriers. For ease of application and stability, ethosomal dispersions are incorporated into gels, patches, and creams. Highly diverse in vivo models are used to evaluate their efficacy in dermal/transdermal delivery, in addition to clinical trials. This article provides a detailed review of the ethosomal systems and categorizes them on the basis of their constituents to classical ethosomes, binary ethosomes, and transethosomes. The differences among these systems are discussed from several perspectives, including the formulation, size, ζ-potential (zeta potential), entrapment efficiency, skin-permeation properties, and stability. This paper gives a detailed review on the effects of ethosomal system constituents, preparation methods, and their significant roles in determining the final properties of these nanocarriers. Furthermore, the novel pharmaceutical dosage forms of ethosomal gels, patches, and creams are highlighted. The article also provides detailed information regarding the in vivo studies and clinical trials conducted for the evaluation of these vesicular systems.

Ethosomal nanocarriers: the impact of constituents and formulation techniques on ethosomal properties, in vivo studies, and clinical trials

PubMed Central

Abdulbaqi, Ibrahim M; Darwis, Yusrida; Khan, Nurzalina Abdul Karim; Assi, Reem Abou; Khan, Arshad A

2016-01-01

Ethosomal systems are novel lipid vesicular carriers containing a relatively high percentage of ethanol. These nanocarriers are especially designed for the efficient delivery of therapeutic agents with different physicochemical properties into deep skin layers and across the skin. Ethosomes have undergone extensive research since they were invented in 1996; new compounds were added to their initial formula, which led to the production of new types of ethosomal systems. Different preparation techniques are used in the preparation of these novel carriers. For ease of application and stability, ethosomal dispersions are incorporated into gels, patches, and creams. Highly diverse in vivo models are used to evaluate their efficacy in dermal/transdermal delivery, in addition to clinical trials. This article provides a detailed review of the ethosomal systems and categorizes them on the basis of their constituents to classical ethosomes, binary ethosomes, and transethosomes. The differences among these systems are discussed from several perspectives, including the formulation, size, ζ-potential (zeta potential), entrapment efficiency, skin-permeation properties, and stability. This paper gives a detailed review on the effects of ethosomal system constituents, preparation methods, and their significant roles in determining the final properties of these nanocarriers. Furthermore, the novel pharmaceutical dosage forms of ethosomal gels, patches, and creams are highlighted. The article also provides detailed information regarding the in vivo studies and clinical trials conducted for the evaluation of these vesicular systems. PMID:27307730

Efficient Self-Assembly of mPEG End-Capped Porous Silica as a Redox-Sensitive Nanocarrier for Controlled Doxorubicin Delivery.

PubMed

Nguyen, Anh Khoa; Nguyen, Thi Hiep; Bao, Bui Quoc; Bach, Long Giang; Nguyen, Dai Hai

2018-01-01

Porous nanosilica (PNS) has been regarded as a promising candidate for controlled delivery of anticancer drugs. Unmodified PNS-based nanocarriers, however, showed a burst release of encapsulated drugs, which may limit their clinical uses. In this report, PNS was surface conjugated with adamantylamine (ADA) via disulfide bridges (-SS-), PNS-SS-ADA, which was further modified with cyclodextrin-poly(ethylene glycol) methyl ether conjugate (CD-mPEG) to form a core@shell structure PNS-SS-ADA@CD-mPEG for redox triggered delivery of doxorubicin (DOX), DOX/PNS-SS-ADA@CD-mPEG. The prepared PNS-SS-ADA@CD-mPEG nanoparticles were spherical in shape with an average diameter of 55.5 ± 3.05 nm, a little larger than their parentally PNS nanocarriers, at 49.6 ± 2.56 nm. In addition, these nanoparticles possessed high drug loading capacity, at 79.2 ± 3.2%, for controlled release. The release of DOX from DOX/PNS-SS-ADA@CD-mPEG nanoparticles was controlled and prolonged up to 120 h in PBS medium (pH 7.4), compared to less than 40 h under reducing condition of 5 mM DTT. Notably, the PNS-SS-ADA@CD-mPEG was a biocompatible nanocarrier, and the toxicity of DOX was dramatically reduced after loading drugs into the porous core. This redox-sensitive PNS-SS-ADA@CD-mPEG nanoparticle could be considered a potential candidate with high drug loading capacity and a lower risk of systemic toxicity.

Study on Interference Suppression Algorithms for Electronic Noses: A Review

PubMed Central

Liang, Zhifang; Zhang, Ci; Sun, Hao; Liu, Tao

2018-01-01

Electronic noses (e-nose) are composed of an appropriate pattern recognition system and a gas sensor array with a certain degree of specificity and broad spectrum characteristics. The gas sensors have their own shortcomings of being highly sensitive to interferences which has an impact on the detection of target gases. When there are interferences, the performance of the e-nose will deteriorate. Therefore, it is urgent to study interference suppression techniques for e-noses. This paper summarizes the sources of interferences and reviews the advances made in recent years in interference suppression for e-noses. According to the factors which cause interference, interferences can be classified into two types: interference caused by changes of operating conditions and interference caused by hardware failures. The existing suppression methods were summarized and analyzed from these two aspects. Since the interferences of e-noses are uncertain and unstable, it can be found that some nonlinear methods have good effects for interference suppression, such as methods based on transfer learning, adaptive methods, etc. PMID:29649152

Gradient-dependent release of the model drug TRITC-dextran from FITC-labeled BSA hydrogel nanocarriers in the hair follicles of porcine ear skin.

PubMed

Tran, Ngo Bich Nga Nathalie; Knorr, Fanny; Mak, Wing Cheung; Cheung, Kwan Yee; Richter, Heike; Meinke, Martina; Lademann, Jürgen; Patzelt, Alexa

2017-07-01

Hair follicle research is currently focused on the development of drug-loaded nanocarriers for the targeting of follicular structures in the treatment of skin and hair follicle-related disorders. In the present study, a dual-label nanocarrier system was implemented in which FITC-labeled BSA hydrogel nanocarriers loaded with the model drug and dye TRITC-dextran were applied topically to porcine ear skin. Follicular penetration and the distribution of both dyes corresponding to the nanocarriers and the model drug in the follicular ducts subsequent to administration to the skin were investigated using confocal laser scanning microscopy. The release of TRITC-dextran from the particles was induced by washing of the nanocarriers, which were kept in a buffer containing TRITC-labeled dextran to balance out the diffusion of the dextran during storage, thereby changing the concentration gradient. The results showed a slightly but statistically significantly deeper follicular penetration of fluorescent signals corresponding to TRITC-dextran as opposed to fluorescence corresponding to the FITC-labeled particles. The different localizations of the dyes in the cross-sections of the skin samples evidenced the release of the model drug from the labeled nanoparticles. Copyright © 2016 Elsevier B.V. All rights reserved.

Histopathology confirms white-nose syndrome in bats in Europe

USGS Publications Warehouse

Pikula, J.; Bandouchova, H.; Novotny, L.; Meteyer, C.U.; Zukal, J.; Irwin, N.R.; Zima, J.; Martinkova, N.

2012-01-01

White-nose syndrome, associated with the fungal skin infection geomycosis, caused regional population collapse in bats in North America. Our results, based on histopathology, show the presence of white-nose syndrome in Europe. Dermatohistopathology on two bats (Myotis myotis) found dead in March 2010 with geomycosis in the Czech Republic had characteristics resembling Geomyces destructans infection in bats confirmed with white-nose syndrome in US hibernacula. In addition, a live M. myotis, biopsied for histopathology during hibernation in April 2011, had typical fungal infection with cupping erosion and invasion of muzzle skin diagnostic for white-nose syndrome and conidiospores identical to G. destructans that were genetically confirmed as G. destructans. ?? Wildlife Disease Association 2012.

Delivery of therapeutics using nanocarriers for targeting cancer cells and cancer stem cells.

PubMed

Krishnamurthy, Sangeetha; Ke, Xiyu; Yang, Yi Yan

2015-01-01

Development of cancer resistance, cancer relapse and metastasis are attributed to the presence of cancer stem cells (CSCs). Eradication of this subpopulation has been shown to increase life expectancy of patients. Since the discovery of CSCs a decade ago, several strategies have been devised to specifically target them but with limited success. Nanocarriers have recently been employed to deliver anti-CSC therapeutics for reducing the population of CSCs at the tumor site with great success. This review discusses the different therapeutic strategies that have been employed using nanocarriers, their advantages, success in targeting CSCs and the challenges that are to be overcome. Exploiting this new modality of cancer treatment in the coming decade may improve outcomes profoundly with promise of effective treatment response and reducing relapse and metastasis.

Never Declared Brain Dead Potential Organ Donors-An Additional Source of Donor Organs?

PubMed

Webster, Patricia A; Markham, Lori E

2018-03-01

Patients never declared brain dead may represent an additional source of donor organs. To determine the number of likely brain dead potential donors who are never declared brain dead and to compare them with brain dead and donation after cardiac death potential organ donors. This study was a retrospective chart review of all catastrophically brain-injured patients referred to a single-organ procurement organization (OPO) over a 4-year period. This study identified 159 likely brain dead potential organ donors, 902 brain dead potential organ donors, and 357 potential donation after circulatory death donors over a 4-year period. None. This study did not predetermine outcome measures before data collection because the study group, likely brain dead potential organ donors, had not previously been described. Likely brain dead potential donors were significantly older than brain dead potential donors ( P < .0001) but were otherwise not different demographically. They were more likely to be a late referral to the OPO ( P < .0001) and less likely to be in the donor registry ( P < .0001). The most commonly identified factors associated with a failure to declare brain death were an unwillingness to continue supportive care by the family, premention of donation, a nontimely imminent death referral, known prior objection to donation, terminal instability, and a lack of cooperation with the OPO.

Recent advancements in the field of nanotechnology for the delivery of anti-Alzheimer drug in the brain region.

PubMed

Agrawal, Mukta; Saraf, Swarnlata; Saraf, Shailendra; Antimisiaris, Sophia G; Hamano, Nobuhito; Li, Shyh-Dar; Chougule, Mahavir; Shoyele, Sunday A; Gupta, Umesh; Ajazuddin; Alexander, Amit

2018-06-01

Brain is supposed to be the most complicated part of the body which is very far from the reach of drug moieties. The drug entry in to the brain region depends upon various factors, and among those, the blood-brain-barrier remains the most prominent one. This barrier restricts the entry of almost all the drug and most of the essential biological components like proteins, peptides, etc. and hinders treatment of the CNS disorders. Alzheimer Disease (AD) is one such brain disorder, more specifically a neurodegenerative disorder which primarily affects the older adults. Areas covered: From solubility enhancement to targeted delivery, the nanoparticulate system became the answer for almost all the criticality related to drug delivery. Hence, nanoparticulate drug carrier system has been widely utilizing to remove the hurdles of brain drug delivery. Keeping this in mind, we have underlined the proficiencies of the nanocarrier systems which claim to improve the drug efficacy for the treatment of the AD. Expert opinion: The nanotechnological approaches are highly exploited by the researchers to enhance the drug permeation across the BBB to improve its bioavailability and efficacy by protecting the drug from peripheral degradation. However, still in this area of drug targeting provides vast scope for discoveries towards the enhancement of drug efficacy through surface modifications, site specification, reduced toxicity of the nanocarrier system and so on.

The Potential of Using Brain Images for Authentication

PubMed Central

Zhou, Zongtan; Shen, Hui; Hu, Dewen

2014-01-01

Biometric recognition (also known as biometrics) refers to the automated recognition of individuals based on their biological or behavioral traits. Examples of biometric traits include fingerprint, palmprint, iris, and face. The brain is the most important and complex organ in the human body. Can it be used as a biometric trait? In this study, we analyze the uniqueness of the brain and try to use the brain for identity authentication. The proposed brain-based verification system operates in two stages: gray matter extraction and gray matter matching. A modified brain segmentation algorithm is implemented for extracting gray matter from an input brain image. Then, an alignment-based matching algorithm is developed for brain matching. Experimental results on two data sets show that the proposed brain recognition system meets the high accuracy requirement of identity authentication. Though currently the acquisition of the brain is still time consuming and expensive, brain images are highly unique and have the potential possibility for authentication in view of pattern recognition. PMID:25126604

The potential of using brain images for authentication.

PubMed

Chen, Fanglin; Zhou, Zongtan; Shen, Hui; Hu, Dewen

2014-01-01

Biometric recognition (also known as biometrics) refers to the automated recognition of individuals based on their biological or behavioral traits. Examples of biometric traits include fingerprint, palmprint, iris, and face. The brain is the most important and complex organ in the human body. Can it be used as a biometric trait? In this study, we analyze the uniqueness of the brain and try to use the brain for identity authentication. The proposed brain-based verification system operates in two stages: gray matter extraction and gray matter matching. A modified brain segmentation algorithm is implemented for extracting gray matter from an input brain image. Then, an alignment-based matching algorithm is developed for brain matching. Experimental results on two data sets show that the proposed brain recognition system meets the high accuracy requirement of identity authentication. Though currently the acquisition of the brain is still time consuming and expensive, brain images are highly unique and have the potential possibility for authentication in view of pattern recognition.

Clinical advances of nanocarrier-based cancer therapy and diagnostics.

PubMed

Luque-Michel, Edurne; Imbuluzqueta, Edurne; Sebastián, Víctor; Blanco-Prieto, María J

2017-01-01

Cancer is a leading cause of death worldwide and efficient new strategies are urgently needed to combat its high mortality and morbidity statistics. Fortunately, over the years, nanotechnology has evolved as a frontrunner in the areas of imaging, diagnostics and therapy, giving the possibility of monitoring, evaluating and individualizing cancer treatments in real-time. Areas covered: Polymer-based nanocarriers have been extensively studied to maximize cancer treatment efficacy and minimize the adverse effects of standard therapeutics. Regarding diagnosis, nanomaterials like quantum dots, iron oxide nanoparticles or gold nanoparticles have been developed to provide rapid, sensitive detection of cancer and, therefore, facilitate early treatment and monitoring of the disease. Therefore, multifunctional nanosystems with both imaging and therapy functionalities bring us a step closer to delivering precision/personalized medicine in the cancer setting. Expert opinion: There are multiple barriers for these new nanosystems to enter the clinic, but it is expected that in the near future, nanocarriers, together with new 'targeted drugs', could replace our current treatments and cancer could become a nonfatal disease with good recovery rates. Joint efforts between scientists, clinicians, the pharmaceutical industry and legislative bodies are needed to bring to fruition the application of nanosystems in the clinical management of cancer.

White-nose syndrome fungus (Geomyces destructans) in bats, Europe

USGS Publications Warehouse

Wibbelt, G.; Kurth, A.; Hellmann, D.; Weishaar, M.; Barlow, A.; Veith, M.; Pruger, J.; Gorfol, T.; Grosche, T.; Bontadina, F.; Zophel, U.; Seidl, Hans-Peter; Cryan, P.M.; Blehert, D.S.

2010-01-01

White-nose syndrome is an emerging disease in North America that has caused substantial declines in hibernating bats. A recently identified fungus (Geomyces destructans) causes skin lesions that are characteristic of this disease. Typical signs of this infection were not observed in bats in North America before white-nose syndrome was detected. However, unconfirmed reports from Europe indicated white fungal growth on hibernating bats without associated deaths. To investigate these differences, hibernating bats were sampled in Germany, Switzerland, and Hungary to determine whether G. destructans is present in Europe. Microscopic observations, fungal culture, and genetic analyses of 43 samples from 23 bats indicated that 21 bats of 5 species in 3 countries were colonized by G. destructans. We hypothesize that G. destructans is present throughout Europe and that bats in Europe may be more immunologically or behaviorally resistant to G. destructans than their congeners in North America because they potentially coevolved with the fungus.

Reversal of multidrug resistance in MCF-7/Adr cells by codelivery of doxorubicin and BCL2 siRNA using a folic acid-conjugated polyethylenimine hydroxypropyl-β-cyclodextrin nanocarrier

PubMed Central

Li, Jin-Ming; Zhang, Wei; Su, Hua; Wang, Yuan-Yuan; Tan, Cai-Ping; Ji, Liang-Nian; Mao, Zong-Wan

2015-01-01

Systemic administration of chemotherapy for cancer often faces drug resistance, limiting its applications in cancer therapy. In this study, we developed a simple multifunctional nanocarrier based on polyethylenimine (PEI) to codeliver doxorubicin (DOX) and BCL2 small interfering RNA (siRNA) for overcoming multidrug resistance (MDR) and enhancing apoptosis in MCF-7/Adr cancer cells by combining chemotherapy and RNA interference (RNAi) therapy. The low-molecular-weight branch PEI was used to conjugate hydroxypropyl-β-cyclodextrin (HP-β-CD) and folic acid (FA), forming the codelivery nanocarrier (FA-HP-β-CD-PEI) to encapsulate DOX with the cavity HP-β-CD and bind siRNA with the positive charge of PEI for tumor-targeting codelivering drugs. The drug-loaded nanocomplexes (FA-HP-β-CD-PEI/DOX/siRNA) showed uniform size distribution, high cellular uptake, and significant gene suppression of BCL2, displaying the potential of overcoming MDR for enhancing the effect of anticancer drugs. Furthermore, the nanocomplexes achieved significant cell apoptosis through a mechanism of downregulating the antiapoptotic protein BCL2, resulted in improving therapeutic efficacy of the coadministered DOX by tumor targeting and RNA interference. Our study indicated that combined RNAi therapy and chemotherapy using our functional codelivery nanocarrier could overcome MDR and enhance apoptosis in MDR cancer cells for a potential application in treating MDR cancers. PMID:25960653

Depicting the inner and outer nose: the representation of the nose and the nasal mucosa on the human primary somatosensory cortex (SI).

PubMed

Gastl, Mareike; Brünner, Yvonne F; Wiesmann, Martin; Freiherr, Jessica

2014-09-01

The nose is important not only for breathing, filtering air, and perceiving olfactory stimuli. Although the face and hands have been mapped, the representation of the internal and external surface of the nose on the primary somatosensory cortex (SI) is still poorly understood. To fill this gap functional magnetic resonance imaging (fMRI) was used to localize the nose and the nasal mucosa in the Brodman areas (BAs) 3b, 1, and 2 of the human postcentral gyrus (PG). Tactile stimulation during fMRI was applied via a customized pneumatically driven device to six stimulation sites: the alar wing of the nose, the lateral nasal mucosa, and the hand (serving as a reference area) on the left and right side of the body. Individual representations could be discriminated for the left and right hand, for the left nasal mucosa and left alar wing of the nose in BA 3b and BA 1 by comparing mean activation maxima and Euclidean distances. Right-sided nasal conditions and conditions in BA 2 could further be separated by different Euclidean distances. Regarding the alar wing of the nose, the results concurred with the classic sensory homunculus proposed by Penfield and colleagues. The nasal mucosa was not only determined an individual and bilateral representation, its position on the somatosensory cortex is also situated closer to the caudal end of the PG compared to that of the alar wing of the nose and the hand. As SI is commonly activated during the perception of odors, these findings underscore the importance of the knowledge of the representation of the nasal mucosa on the primary somatosensory cortex, especially for interpretation of results of functional imaging studies about the sense of smell. Copyright © 2014 Wiley Periodicals, Inc.

[Simulation and air-conditioning in the nose].

PubMed

Keck, T; Lindemann, J

2010-05-01

Heating and humidification of the respiratory air are the main functions of the nasal airways in addition to cleansing and olfaction. Optimal nasal air conditioning is mandatory for an ideal pulmonary gas exchange in order to avoid dessication and adhesion of the alveolar capillary bed. The complex three-dimensional anatomical structure of the nose makes it impossible to perform detailed in vivo studies on intranasal heating and humidification within the entire nasal airways applying various technical set-ups. The main problem of in vivo temperature and humidity measurements is a poor spatial and time resolution. Therefore, in vivo measurements are feasible to a restricted extent, only providing single temperature values as the complete nose is not entirely accessible. Therefore, data on the overall performance of the nose are only based on one single measurement within each nasal segment. In vivo measurements within the entire nose are not feasible. These serious technical issues concerning in vivo measurements led to a large number of numerical simulation projects in the last few years providing novel information about the complex functions of the nasal airways. In general, numerical simulations only calculate predictions in a computational model, e. g. realistic nose model, depending on the setting of the boundary conditions. Therefore, numerical simulations achieve only approximations of a possible real situation. The aim of this report is the synopsis of the technical expertise on the field of in vivo nasal air conditioning, the novel information of numerical simulations and the current state of knowledge on the influence of nasal and sinus surgery on nasal air conditioning.

Designing Dendrimer and Miktoarm Polymer Based Multi-Tasking Nanocarriers for Efficient Medical Therapy.

PubMed

Sharma, Anjali; Kakkar, Ashok

2015-09-17

To address current complex health problems, there has been an increasing demand for smart nanocarriers that could perform multiple complimentary biological tasks with high efficacy. This has provoked the design of tailor made nanocarriers, and the scientific community has made tremendous effort in meeting daunting challenges associated with synthetically articulating multiple functions into a single scaffold. Branched and hyper-branched macromolecular architectures have offered opportunities in enabling carriers with capabilities including location, delivery, imaging etc. Development of simple and versatile synthetic methodologies for these nanomaterials has been the key in diversifying macromolecule based medical therapy and treatment. This review highlights the advancement from conventional "only one function" to multifunctional nanomedicine. It is achieved by synthetic elaboration of multivalent platforms in miktoarm polymers and dendrimers by physical encapsulation, covalent linking and combinations thereof.

Pediatric Obesity and Ear, Nose, and Throat Disorders

MedlinePlus

... Marketplace Find an ENT Doctor Near You Pediatric Obesity and Ear, Nose, and Throat Disorders Pediatric Obesity ... self-esteem, and isolation from their peers. Pediatric obesity and otolaryngic problems Otolaryngologists, or ear, nose, and ...

Glucose-Coated Gold Nanoparticles Transfer across Human Brain Endothelium and Enter Astrocytes In Vitro

PubMed Central

Gromnicova, Radka; Davies, Heather A.; Sreekanthreddy, Peddagangannagari; Romero, Ignacio A.; Lund, Torben; Roitt, Ivan M.; Phillips, James B.; Male, David K.

2013-01-01

The blood-brain barrier prevents the entry of many therapeutic agents into the brain. Various nanocarriers have been developed to help agents to cross this barrier, but they all have limitations, with regard to tissue-selectivity and their ability to cross the endothelium. This study investigated the potential for 4 nm coated gold nanoparticles to act as selective carriers across human brain endothelium and subsequently to enter astrocytes. The transfer rate of glucose-coated gold nanoparticles across primary human brain endothelium was at least three times faster than across non-brain endothelia. Movement of these nanoparticles occurred across the apical and basal plasma membranes via the cytosol with relatively little vesicular or paracellular migration; antibiotics that interfere with vesicular transport did not block migration. The transfer rate was also dependent on the surface coating of the nanoparticle and incubation temperature. Using a novel 3-dimensional co-culture system, which includes primary human astrocytes and a brain endothelial cell line hCMEC/D3, we demonstrated that the glucose-coated nanoparticles traverse the endothelium, move through the extracellular matrix and localize in astrocytes. The movement of the nanoparticles through the matrix was >10 µm/hour and they appeared in the nuclei of the astrocytes in considerable numbers. These nanoparticles have the correct properties for efficient and selective carriers of therapeutic agents across the blood-brain barrier. PMID:24339894

Deprivation selectively modulates brain potentials to food pictures.

PubMed

Stockburger, Jessica; Weike, Almut I; Hamm, Alfons O; Schupp, Harald T

2008-08-01

Event-related brain potentials (ERPs) were used to examine whether the processing of food pictures is selectively modulated by changes in the motivational state of the observer. Sixteen healthy male volunteers were tested twice 1 week apart, either after 24 hr of food deprivation or after normal food intake. ERPs were measured while participants viewed appetitive food pictures as well as standard emotional and neutral control pictures. Results show that the ERPs to food pictures in a hungry, rather than satiated, state were associated with enlarged positive potentials over posterior sensor sites in a time window of 170-310 ms poststimulus. Minimum-norm analysis suggests the enhanced processing of food cues primarily in occipito-temporo-parietal regions. In contrast, processing of standard emotional and neutral pictures was not modulated by food deprivation. Considered from the perspective of motivated attention, the selective change of food cue processing may reflect a state-dependent change in stimulus salience.

21 CFR 868.5375 - Heat and moisture condenser (artificial nose).

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Heat and moisture condenser (artificial nose). 868... SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5375 Heat and moisture condenser (artificial nose). (a) Identification. A heat and moisture condenser (artificial nose...

21 CFR 868.5375 - Heat and moisture condenser (artificial nose).

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Heat and moisture condenser (artificial nose). 868... SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5375 Heat and moisture condenser (artificial nose). (a) Identification. A heat and moisture condenser (artificial nose...

Absorption and Biodistribution of Nanoparticles in Mouse, Caenorhabditis elegans, Arabidopsis thaliana and Nicotina bethamiana

NASA Astrophysics Data System (ADS)

Al Awwad, Nasir

Nanotechnology is the arrangement of materials, and devices which permit technology to operate in nanometer-sized objects. Some of the potential applications of these nanomaterials include light harvesting for solar cells, light emitting enhancer for LEDs, cosmetics, and nanocarriers for pesticide applications and drug delivery. The impact of nanomaterials on the environment is a concern. The Lam laboratory has developed a novel nanocarrier system for the delivery of hydrophobic drugs or imaging agents against tumors. This nanocarriers are based on polyethylene glycol-cholic acid cluster telodendrimers which can self-assemble to form micellar structure. Here we report on the ability of these nanocarriers to cross the blood brain barrier (BBB) in murine model, and the GI absorption of the nanocarrier in Caenorhabditis elegans models. In addition, we also studied the uptake of the nanocarriers by Arabidopsis Thaliana seedlings and Nicotina bethamiana leaves, Application of three different biological organisms were used, one mammalian, one invertebrate, and one plant. Drug delivery to the central nervous system is not easy as compared to other body organs due to the presence of the BBB. It is essential that any delivery system to the central nervous system (CNS) needs to be efficient and non-toxic. Adenosine receptor agonists have been reported to be able to modulate the permeability of the BBB to macromolecules. Here, we studied the effect of 5'-(NEthylcarboxamido) (NECA), an adenosine receptor agonist, on the penetration of both non-crosslinked micelle (NCM) and disulfide cross-linked micelle (DCM) through the blood brain barrier into the brain parenchyma. We found that NECA given at 5.3 mg/kg intravenously, was able to facilitate the delivery of fluorescentlabeled NCM, DCM and polyvinyl alcohol (PVA) based nanocarriers to organs or blood vessels expressing adenosine receptors, which also include the brain. After ingestion, both DCM and NCM were localized inside the

Prospective Study of the Surgical Techniques Used in Primary Rhinoplasty on the Caucasian Nose and Comparison of the Preoperative and Postoperative Anthropometric Nose Measurements

PubMed Central

Berger, Cezar Augusto Sarraf; Freitas, Renato da Silva; Malafaia, Osvaldo; Pinto, José Simão de Paula; Macedo Filho, Evaldo Dacheux; Mocellin, Marcos; Fagundes, Marina Serrato Coelho

2014-01-01

Introduction The knowledge and study of surgical techniques and anthropometric measurements of the nose make possible a qualitative and quantitative analysis of surgical results. Objective Study the main technique used in rhinoplasty on Caucasian noses and compare preoperative and postoperative anthropometric measurements of the nose. Methods A prospective study with 170 patients was performed at a private hospital. Data were collected using the Electronic System Integrated of Protocols software (Sistema Integrado de Protocolos Eletrônicos, SINPE©). The surgical techniques used in the nasal dorsum and tip were evaluated. Preoperative and 12-month follow-up photos as well as the measurements compared with the ideal aesthetic standard of a Caucasian nose were analyzed objectively. Student t test and standard deviation test were applied. Results There was a predominance of endonasal access (94.4%). The most common dorsum technique was hump removal (33.33%), and the predominance of sutures (24.76%) was observed on the nasal tip, with the lateral intercrural the most frequent (32.39%). Comparison between preoperative and postoperative photos found statistically significant alterations on the anthropometric measurements of the noses. Conclusion The main surgical techniques on Caucasian noses were evaluated, and a great variety was found. The evaluation of anthropometric measurements of the nose proved the efficiency of the performed procedures. PMID:25992149

Detecting aroma changes of local flavored green tea (Camellia sinensis) using electronic nose

NASA Astrophysics Data System (ADS)

Ralisnawati, D.; Sukartiko, A. C.; Suryandono, A.; Triyana, K.

2018-03-01

Indonesia is currently the sixth largest tea producer in the world. However, consumption of the product in the country was considered low. Besides tea, the country also has various local flavor ingredients that are potential to be developed. The addition of local flavored ingredients such as ginger, lemon grass, and lime leaves on green tea products is gaining acceptance from consumers and producers. The aroma of local flavored green tea was suspected to changes during storage, while its sensory testing has some limitations. Therefore, the study aimed to detect aroma changes of local flavors added in green tea using electronic nose (e-nose), an instrument developed to mimic the function of the human nose. The test was performed on a four-gram sample. The data was collected with 120 seconds of sensing time and 60 seconds of blowing time. Principal Component Analysis (PCA) was used to find out the aroma changes of local flavored green tea during storage. We observed that electronic nose could detect aroma changes of ginger flavored green tea from day 0 to day 6 with variance percentage 99.6%. Variance proportion of aroma changes of lemon grass flavored green tea from day 0 to day 6 was 99.3%. Variance proportion of aroma changes of lime leaves flavored green tea from day 0 to day 6 was 99.4%.

Wasabi nose: an underreported complication of cyclophosphamide infusions.

PubMed

Janow, Ginger L; Ilowite, Norman T; Wahezi, Dawn M

2011-07-01

Wasabi nose, a term used to describe the nasopharyngeal discomfort experienced during cyclophosphamide infusions, is a rare phenomenon, previously described in case reports of adult oncology patients typically receiving high-dose chemotherapy regimens. The underlying mechanism by which this phenomenon occurs is unknown. We report four cases of children with rheumatic diseases afflicted by profound nasopharyngeal discomfort secondary to low-dose cyclophosphamide infusions. We additionally review the literature regarding potential medical management of these complications and describe our experience using these interventions.

Anaphoric Reference to Quantified Antecedents: An Event-Related Brain Potential Study

ERIC Educational Resources Information Center

Filik, Ruth; Leuthold, Hartmut; Moxey, Linda M.; Sanford, Anthony J.

2011-01-01

We report an event-related brain potential (ERP) study examining how readers process sentences containing anaphoric reference to quantified antecedents. Previous studies indicate that positive (e.g. "many") and negative (e.g. "not many") quantifiers cause readers to focus on different sets of entities. For example in "Many of the fans attended the…

Identifying Septal Support Reconstructions for Saddle Nose Deformity: The Cakmak Algorithm.

PubMed

Cakmak, Ozcan; Emre, Ismet Emrah; Ozkurt, Fazil Emre

2015-01-01

The saddle nose deformity is one of the most challenging problems in nasal surgery with a less predictable and reproducible result than other nasal procedures. The main feature of this deformity is loss of septal support with both functional and aesthetic implications. Most reports on saddle nose have focused on aesthetic improvement and neglected the reestablishment of septal support to improve airway. To explain how the Cakmak algorithm, an algorithm that describes various fixation techniques and grafts in different types of saddle nose deformities, aids in identifying saddle nose reconstructions that restore supportive nasal framework and provide the aesthetic improvements typically associated with procedures to correct saddle nose deformities. This algorithm presents septal support reconstruction of patients with saddle nose deformity based on the experience of the senior author in 206 patients with saddle nose deformity. Preoperative examination, intraoperative assessment, reconstruction techniques, graft materials, and patient evaluation of aesthetic success were documented, and 4 different types of saddle nose deformities were defined. The Cakmak algorithm classifies varying degrees of saddle nose deformity from type 0 to type 4 and helps identify the most appropriate surgical procedure to restore the supportive nasal framework and aesthetic dorsum. Among the 206 patients, 110 women and 96 men, mean (range) age was 39.7 years (15-68 years), and mean (range) of follow-up was 32 months (6-148 months). All but 12 patients had a history of previous nasal surgeries. Application of the Cakmak algorithm resulted in 36 patients categorized with type 0 saddle nose deformities; 79, type 1; 50, type 2; 20, type 3a; 7, type 3b; and 14, type 4. Postoperative photographs showed improvement of deformities, and patient surveys revealed aesthetic improvement in 201 patients and improvement in nasal breathing in 195 patients. Three patients developed postoperative infection

21 CFR 868.5375 - Heat and moisture condenser (artificial nose).

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Heat and moisture condenser (artificial nose). 868.5375 Section 868.5375 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... moisture condenser (artificial nose). (a) Identification. A heat and moisture condenser (artificial nose...

21 CFR 868.5375 - Heat and moisture condenser (artificial nose).

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Heat and moisture condenser (artificial nose). 868.5375 Section 868.5375 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... moisture condenser (artificial nose). (a) Identification. A heat and moisture condenser (artificial nose...

21 CFR 868.5375 - Heat and moisture condenser (artificial nose).

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Heat and moisture condenser (artificial nose). 868.5375 Section 868.5375 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... moisture condenser (artificial nose). (a) Identification. A heat and moisture condenser (artificial nose...

Copper transport mediated by nanocarrier systems in a blood-brain barrier in vitro model.

PubMed

Fehse, Susanne; Nowag, Sabrina; Quadir, Mohiuddin; Kim, Kwang Sik; Haag, Rainer; Multhaup, Gerd

2014-05-12

Copper (Cu) is a cofactor of various metalloenzymes and has a role in neurodegenerative diseases with disturbed Cu homeostasis, for example, in Alzheimer's disease (AD) and Menkes disease. To address Cu imbalances, we synthesized two different dendritic nanoparticles (NP) for the transport of Cu(II) ions across the blood-brain barrier (BBB). The synthesized NPs show low toxicity and high water solubility and can stabilize high amounts of Cu(II). The Cu(II)-laden NPs crossed cellular membranes and increased the cellular Cu level. A human brain microvascular endothelial cell (HBMEC) model was established to investigate the permeability of the NPs through the BBB. By comparing the permeability × surface area product (PSe) of reference substances with those of NPs, we observed that NPs crossed the BBB model two times more effectively than (14)C-sucrose and sodium fluorescein (NaFl) and up to 60× better than Evans Blue labeled albumin (EBA). Our results clearly indicate that NPs cross the BBB model effectively. Furthermore, Cu was shielded by the NPs, which decreased the Cu toxicity. The novel design of the core-shell NP enabled the complexation of Cu(II) in the outer shell and therefore facilitated the pH-dependent release of Cu in contrast to core-multishell NPs, where the Cu(II) ions are encapsulated in the core. This allows a release of Cu into the cytoplasm. In addition, by using a cellular detection system based on a metal response element with green fluorescent protein (MRE-GFP), we demonstrated that Cu could also be released intracellularly from NPs and is accessible for biological processes. Our results indicate that NPs are potential candidates to rebalance metal-ion homeostasis in disease conditions affecting brain and neuronal systems.

Numerical simulation of humidification and heating during inspiration within an adult nose.

PubMed

Sommer, F; Kroger, R; Lindemann, J

2012-06-01

The temperature of inhaled air is highly relevant for the humidification process. Narrow anatomical conditions limit possibilities for in vivo measurements. Numerical simulations offer a great potential to examine the function of the human nose. In the present study, the nasal humidification of inhaled air was simulated simultaneously with temperature distribution during a respiratory cycle. A realistic nose model based on a multislice CT scan was created. The simulation was performed by the Software Fluent(r). Boundary conditions were based on previous in vivo measurements. Inhaled air had a temperature of 20(deg)C and relative humidity of 30%. The wall temperature was assumed to be variable from 34(deg)C to 30(deg)C with constant humidity saturation of 100% during the respiratory cycle. A substantial increase in temperature and humidity can be observed after passing the nasal valve area. Areas with high speed air flow, e.g. the space around the turbinates, show an intensive humidification and heating potential. Inspired air reaches 95% humidity and 28(deg)C within the nasopharynx. The human nose features an enormous humidification and heating capability. Warming and humidification are dependent on each other and show a similar spacial pattern. Concerning the climatisation function, the middle turbinate is of high importance. In contrast to in vivo measurements, numerical simulations can explore the impact of airflow distribution on nasal air conditioning. They are an effective method to investigate nasal pathologies and impacts of surgical procedures.

Mice with a "monoclonal nose": perturbations in an olfactory map impair odor discrimination.

PubMed

Fleischmann, Alexander; Shykind, Benjamin M; Sosulski, Dara L; Franks, Kevin M; Glinka, Meredith E; Mei, Dan Feng; Sun, Yonghua; Kirkland, Jennifer; Mendelsohn, Monica; Albers, Mark W; Axel, Richard

2008-12-26

We have altered the neural representation of odors in the brain by generating a mouse with a "monoclonal nose" in which greater than 95% of the sensory neurons express a single odorant receptor, M71. As a consequence, the frequency of sensory neurons expressing endogenous receptor genes is reduced 20-fold. We observe that these mice can smell, but odor discrimination and performance in associative olfactory learning tasks are impaired. However, these mice cannot detect the M71 ligand acetophenone despite the observation that virtually all sensory neurons and glomeruli are activated by this odor. The M71 transgenic mice readily detect other odors in the presence of acetophenone. These observations have implications for how receptor activation in the periphery is represented in the brain and how these representations encode odors.

A new therapeutic strategy for lengthening severe short nose.

PubMed

Rikimaru, Hideaki; Kiyokawa, Kensuke; Watanabe, Koichi; Koga, Noriyuki; Nishi, Yukiko

2010-03-01

Correction of severe short nose is a distressing problem for plastic surgeons. It is difficult to simultaneously lengthen the 3 components of the nose, which are the outer skin envelope, the framework, and the mucosal lining. We developed a new method to lengthen the nose more than 10 mm definitively and safely, which was performed using the technique of distraction osteogenesis. The procedure involves a 2-stage operation. At the first stage, boat-shaped iliac bone is grafted on the dorsum. More than 6 months later, the second-stage operation is performed. The grafted bone is cut horizontally in the center, and the distraction device is applied to it. Distraction osteogenesis is started after a latency period of 14 days and performed at a rate of 0.6 mm once daily. The distraction device is replaced by a special attachment (Ribbond; Ribbond Inc) during the 3-month consolidation period. Our method was applied for 2 patients with congenitally and posttraumatic severe short nose, respectively. The total amount of distraction osteogenesis was 12.6 and 13.8 mm, respectively. The profiles of both of the patients improved, and they were satisfied with the results. The method we developed is an entirely new approach to the correction of severe short nose. Furthermore, it was determined that nonvascularized grafted iliac bone could be lengthened by distraction osteogenesis. Our new method was a very effective and definitive technique and could become a mainstream procedure for the correction of severe short nose.

Development of coated liposomes loaded with ghrelin for nose-to-brain delivery for the treatment of cachexia

PubMed Central

Salade, Laurent; Wauthoz, Nathalie; Deleu, Magali; Vermeersch, Marjorie; De Vriese, Carine; Amighi, Karim; Goole, Jonathan

2017-01-01

The aim of the present study was to develop a ghrelin-containing formulation based on liposomes coated with chitosan intended for nose–brain delivery for the treatment of cachexia. Among the three types of liposomes developed, anionic liposomes provided the best results in terms of encapsulation efficiency (56%) and enzymatic protection against trypsin (20.6% vs 0% for ghrelin alone) and carboxylesterase (81.6% vs 17.2% for ghrelin alone). Ghrelin presented both electrostatic and hydrophobic interactions with the anionic lipid bilayer, as demonstrated by isothermal titration calorimetry. Then, anionic liposomes were coated with N-(2-hydroxy) propyl-3-trimethyl ammonium chitosan chloride. The coating involved a size increment from 146.9±2.7 to 194±6.1 nm, for uncoated and coated liposomes, respectively. The ζ-potential was similarly increased from -0.3±1.2 mV to 6±0.4 mV before and after coating, respectively. Chitosan provided mucoadhesion, with an increase in mucin adsorption of 22.9%. Enhancement of permeation through the Calu3 epithelial monolayer was also observed with 10.8% of ghrelin recovered in the basal compartment in comparison to 0% for ghrelin alone. Finally, aerosols generated from two nasal devices (VP3 and SP270) intended for aqueous dispersion were characterized with either coated or uncoated liposomes. Contrarily to the SP270 device, VP3 device showed minor changes between coated and uncoated liposome aerosols, as shown by their median volume diameters of 38.4±5.76 and 37.6±5.74 µm, respectively. Overall, the results obtained in this study show that the developed formulation delivered by the VP3 device can be considered as a potential candidate for nose–brain delivery of ghrelin. PMID:29238190

Application of dental nanomaterials: potential toxicity to the central nervous system

PubMed Central

Feng, Xiaoli; Chen, Aijie; Zhang, Yanli; Wang, Jianfeng; Shao, Longquan; Wei, Limin

2015-01-01

Nanomaterials are defined as materials with one or more external dimensions with a size of 1–100 nm. Such materials possess typical nanostructure-dependent properties (eg, chemical, biological, optical, mechanical, and magnetic), which may differ greatly from the properties of their bulk counterparts. In recent years, nanomaterials have been widely used in the production of dental materials, particularly in light polymerization composite resins and bonding systems, coating materials for dental implants, bioceramics, endodontic sealers, and mouthwashes. However, the dental applications of nanomaterials yield not only a significant improvement in clinical treatments but also growing concerns regarding their biosecurity. The brain is well protected by the blood–brain barrier (BBB), which separates the blood from the cerebral parenchyma. However, in recent years, many studies have found that nanoparticles (NPs), including nanocarriers, can transport through the BBB and locate in the central nervous system (CNS). Because the CNS may be a potential target organ of the nanomaterials, it is essential to determine the neurotoxic effects of NPs. In this review, possible dental nanomaterials and their pathways into the CNS are discussed, as well as related neurotoxicity effects underlying the in vitro and in vivo studies. Finally, we analyze the limitations of the current testing methods on the toxicological effects of nanomaterials. This review contributes to a better understanding of the nano-related risks to the CNS as well as the further development of safety assessment systems. PMID:25999717

Application of dental nanomaterials: potential toxicity to the central nervous system.

PubMed

Feng, Xiaoli; Chen, Aijie; Zhang, Yanli; Wang, Jianfeng; Shao, Longquan; Wei, Limin

2015-01-01

Nanomaterials are defined as materials with one or more external dimensions with a size of 1-100 nm. Such materials possess typical nanostructure-dependent properties (eg, chemical, biological, optical, mechanical, and magnetic), which may differ greatly from the properties of their bulk counterparts. In recent years, nanomaterials have been widely used in the production of dental materials, particularly in light polymerization composite resins and bonding systems, coating materials for dental implants, bioceramics, endodontic sealers, and mouthwashes. However, the dental applications of nanomaterials yield not only a significant improvement in clinical treatments but also growing concerns regarding their biosecurity. The brain is well protected by the blood-brain barrier (BBB), which separates the blood from the cerebral parenchyma. However, in recent years, many studies have found that nanoparticles (NPs), including nanocarriers, can transport through the BBB and locate in the central nervous system (CNS). Because the CNS may be a potential target organ of the nanomaterials, it is essential to determine the neurotoxic effects of NPs. In this review, possible dental nanomaterials and their pathways into the CNS are discussed, as well as related neurotoxicity effects underlying the in vitro and in vivo studies. Finally, we analyze the limitations of the current testing methods on the toxicological effects of nanomaterials. This review contributes to a better understanding of the nano-related risks to the CNS as well as the further development of safety assessment systems.

Tumor-targeting delivery of herb-based drugs with cell-penetrating/tumor-targeting peptide-modified nanocarriers

PubMed Central

Kebebe, Dereje; Liu, Yuanyuan; Wu, Yumei; Vilakhamxay, Maikhone; Liu, Zhidong; Li, Jiawei

2018-01-01

Cancer has become one of the leading causes of mortality globally. The major challenges of conventional cancer therapy are the failure of most chemotherapeutic agents to accumulate selectively in tumor cells and their severe systemic side effects. In the past three decades, a number of drug delivery approaches have been discovered to overwhelm the obstacles. Among these, nanocarriers have gained much attention for their excellent and efficient drug delivery systems to improve specific tissue/organ/cell targeting. In order to enhance targeting efficiency further and reduce limitations of nanocarriers, nanoparticle surfaces are functionalized with different ligands. Several kinds of ligand-modified nanomedicines have been reported. Cell-penetrating peptides (CPPs) are promising ligands, attracting the attention of researchers due to their efficiency to transport bioactive molecules intracellularly. However, their lack of specificity and in vivo degradation led to the development of newer types of CPP. Currently, activable CPP and tumor-targeting peptide (TTP)-modified nanocarriers have shown dramatically superior cellular specific uptake, cytotoxicity, and tumor growth inhibition. In this review, we discuss recent advances in tumor-targeting strategies using CPPs and their limitations in tumor delivery systems. Special emphasis is given to activable CPPs and TTPs. Finally, we address the application of CPPs and/or TTPs in the delivery of plant-derived chemotherapeutic agents. PMID:29563797

PEGylated Polyamidoamine dendrimer conjugated with tumor homing peptide as a potential targeted delivery system for glioma.

PubMed

Jiang, Yan; Lv, Lingyan; Shi, Huihui; Hua, Yabing; Lv, Wei; Wang, Xiuzhen; Xin, Hongliang; Xu, Qunwei

2016-11-01

Glioblastoma multiforme (GBM) is the most common and aggressive primary central nervous system (CNS) tumor with a short survival time. The failure of chemotherapy is ascribed to the low transport of chemotherapeutics across the Blood Brain Tumor Barrier (BBTB) and poor penetration into tumor tissue. In order to overcome the two barriers, small nanoparticles with active targeted capability are urgently needed for GBM drug delivery. In this study, we proposed PEGylated Polyamidoamine (PAMAM) dendrimer nanoparticles conjugated with glioma homing peptides (Pep-1) as potential glioma targeting delivery system (Pep-PEG-PAMAM), where PEGylated PAMAM dendrimer nanoparticle was utilized as carrier due to its small size and perfect penetration into tumor and Pep-1 was used to overcome BBTB via interleukin 13 receptor α2 (IL-13Rα2) mediated endocytosis. The preliminary availability and safety of Pep-PEG-PAMAM as a nanocarrier for glioma was evaluated. In vitro results indicated that a significantly higher amount of Pep-PEG-PAMAM was endocytosed by U87 MG cells. In vivo fluorescence imaging of U87MG tumor-bearing mice confirmed that the fluorescence intensity at glioma site of targeted group was 2.02 folds higher than that of untargeted group (**p<0.01), and glioma distribution experiment further revealed that Pep-PEG-PAMAM exhibited a significantly enhanced accumulation and improved penetration at tumor site. In conclusion, Pep-1 modified PAMAM was a promising nanocarrier for targeted delivery of brain glioma. Copyright © 2016 Elsevier B.V. All rights reserved.

Nanocarrier mediated retinal drug delivery: overcoming ocular barriers to treat posterior eye diseases.

PubMed

Bisht, Rohit; Mandal, Abhirup; Jaiswal, Jagdish K; Rupenthal, Ilva D

2018-03-01

Effective drug delivery to the retina still remains a challenge due to ocular elimination mechanisms and complex barriers that selectively limit the entry of drugs into the eye. To overcome these barriers, frequent intravitreal injections are currently used to achieve high drug concentrations in vitreous and retina. However, these repetitive injections may result in several side effects. Recent advancements in the field of nanoparticle-based drug delivery could overcome some of these unmet needs and various preclinical studies conducted to date have demonstrated promising results of nanotherapies in the treatment of retinal diseases. Compared to the majority of commercially available ocular implants, the biodegradable nature of most nanoparticles (NPs) avoids the need for surgical implantation and removal after the release of the payload. In addition, the sustained drug release from NPs over an extended period of time reduces the need for frequent intravitreal injections and the risk of associated side effects. The nanometer size and highly modifiable surface properties make NPs excellent candidates for targeted ocular drug delivery. Studies have shown that nanocarriers enhance the intravitreal half-life and thus bioavailability of a number of drugs including proteins and peptides. In addition, they have shown promising results in delivering genetic material to the retinal tissues by protecting it from possible intravitreal degradation. This review covers the various challenges associated with drug delivery to the posterior segment of the eye, particularly the retina, and highlights the application of nanocarriers to overcome these challenges in context with recent advances in preclinical studies. WIREs Nanomed Nanobiotechnol 2018, 10:e1473. doi: 10.1002/wnan.1473 This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Implantable Materials and Surgical Technologies > Nanomaterials and Implants. © 2017 Wiley Periodicals

Identification of Chinese Herbal Medicines with Electronic Nose Technology: Applications and Challenges.

PubMed

Zhou, Huaying; Luo, Dehan; GholamHosseini, Hamid; Li, Zhong; He, Jiafeng

2017-05-09

This paper provides a review of the most recent works in machine olfaction as applied to the identification of Chinese Herbal Medicines (CHMs). Due to the wide variety of CHMs, the complexity of growing sources and the diverse specifications of herb components, the quality control of CHMs is a challenging issue. Much research has demonstrated that an electronic nose (E-nose) as an advanced machine olfaction system, can overcome this challenge through identification of the complex odors of CHMs. E-nose technology, with better usability, high sensitivity, real-time detection and non-destructive features has shown better performance in comparison with other analytical techniques such as gas chromatography-mass spectrometry (GC-MS). Although there has been immense development of E-nose techniques in other applications, there are limited reports on the application of E-noses for the quality control of CHMs. The aim of current study is to review practical implementation and advantages of E-noses for robust and effective odor identification of CHMs. It covers the use of E-nose technology to study the effects of growing regions, identification methods, production procedures and storage time on CHMs. Moreover, the challenges and applications of E-nose for CHM identification are investigated. Based on the advancement in E-nose technology, odor may become a new quantitative index for quality control of CHMs and drug discovery. It was also found that more research could be done in the area of odor standardization and odor reproduction for remote sensing.

Diverse Applications of Electronic-Nose Technologies in Agriculture and Forestry

Treesearch

Alphus D. Wilson

2013-01-01

Electronic-nose (e-nose) instruments, derived from numerous types of aroma-sensor technologies, have been developed for a diversity of applications in the broad fields of agriculture and forestry. Recent advances in e-nose technologies within the plant sciences, including improvements in gas-sensor designs, innovations in data analysis and pattern-recognition...

Odor source identification by grounding linguistic descriptions in an artificial nose

NASA Astrophysics Data System (ADS)

Loutfi, Amy; Coradeschi, Silvia; Duckett, Tom; Wide, Peter

2001-03-01

This paper addresses the problem of enabling autonomous agents (e.g., robots) to carry out human oriented tasks using an electronic nose. The nose consists of a combination of passive gas sensors with different selectivity, the outputs of which are fused together with an artificial neural network in order to recognize various human-determined odors. The basic idea is to ground human-provided linguistic descriptions of these odors in the actual sensory perceptions of the nose through a process of supervised learning. Analogous to the human nose, the paper explains a method by which an electronic nose can be used for substance identification. First, the receptors of the nose are exposed to a substance by means of inhalation with an electric pump. Then a chemical reaction takes place in the gas sensors over a period of time and an artificial neural network processes the resulting sensor patterns. This network was trained to recognize a basic set of pure substances such as vanilla, lavender and yogurt under controlled laboratory conditions. The complete system was then validated through a series of experiments on various combinations of the basic substances. First, we showed that the nose was able to consistently recognize unseen samples of the same substances on which it had been trained. In addition, we presented some first results where the nose was tested on novel combinations of substances on which it had not been trained by combining the learned descriptions - for example, it could distinguish lavender yogurt as a combination of lavender and yogurt.

Investigating large-scale brain dynamics using field potential recordings: analysis and interpretation.

PubMed

Pesaran, Bijan; Vinck, Martin; Einevoll, Gaute T; Sirota, Anton; Fries, Pascal; Siegel, Markus; Truccolo, Wilson; Schroeder, Charles E; Srinivasan, Ramesh

2018-06-25

New technologies to record electrical activity from the brain on a massive scale offer tremendous opportunities for discovery. Electrical measurements of large-scale brain dynamics, termed field potentials, are especially important to understanding and treating the human brain. Here, our goal is to provide best practices on how field potential recordings (electroencephalograms, magnetoencephalograms, electrocorticograms and local field potentials) can be analyzed to identify large-scale brain dynamics, and to highlight critical issues and limitations of interpretation in current work. We focus our discussion of analyses around the broad themes of activation, correlation, communication and coding. We provide recommendations for interpreting the data using forward and inverse models. The forward model describes how field potentials are generated by the activity of populations of neurons. The inverse model describes how to infer the activity of populations of neurons from field potential recordings. A recurring theme is the challenge of understanding how field potentials reflect neuronal population activity given the complexity of the underlying brain systems.

Cytosolic co-delivery of miRNA-34a and docetaxel with core-shell nanocarriers via caveolae-mediated pathway for the treatment of metastatic breast cancer

NASA Astrophysics Data System (ADS)

Zhang, Li; Yang, Xin; Lv, Yaqi; Xin, Xiaofei; Qin, Chao; Han, Xiaopeng; Yang, Lei; He, Wei; Yin, Lifang

2017-04-01

Co-delivery of microRNAs and chemotherapeutic drugs into tumor cells is an attractive strategy for synergetic breast cancer therapy due to their complementary mechanisms. In this work, a core-shell nanocarrier coated by cationic albumin was developed to simultaneously deliver miRNA-34a and docetaxel (DTX) into breast cancer cells for improved therapeutic effect. The co-delivery nanocarriers showed a spherical morphology with an average particle size of 183.9 nm, and they efficiently protected miRNA-34a from degradation by RNase and serum. Importantly, the nanocarriers entered the cytosol via a caveolae-mediated pathway without entrapment in endosomes/lysosomes, thus improving the utilization of the cargo. In vitro, the co-delivery nanocarriers suppressed the expression of anti-apoptosis gene Bcl-2 at both transcription and protein levels, inhibited tumor cell migration and efficiently induced cell apoptosis and cytotoxicity. In vivo, the co-delivery nanocarriers prolonged the blood circulation of DTX, enhanced tumor accumulation of the cargo and significantly inhibited tumor growth and metastasis in 4T1-tumor bearing mice models. Taken together, the present nanocarrier co-loading with DTX and miRNA-34a is a new nanoplatform for the combination of insoluble drugs and gene/protein drugs and provides a promising strategy for the treatment of metastatic breast cancer.

Brain Event-Related Potential Correlates of Concept Learning.

ERIC Educational Resources Information Center

Federico, Pat-Anthony

An irrelevant auditory probe procedure was used to evoke brain event-related potentials (ERPs) in 56 Navy recruits while they learned pulsed radar concepts presented to them in study booklets. A mastery test was administered to assess concept acquisition. The research issue was whether brain ERPs recorded while students are in the process of…

Encapsulation of a proteasome inhibitor with gold-polysaccharide nanocarriers

NASA Astrophysics Data System (ADS)

Coelho, Sílvia Castro; Rocha, Sandra; Sampaio, Paula; Pereira, Maria Carmo; Coelho, Manuel A. N.

2014-04-01

Organic-inorganic hybrid nanoparticles are potential effective systems for drug delivery in cancer therapy and diagnosis. Chitosan-gum arabic with entrapped gold nanoparticles were developed as a carrier for an anticancer drug bortezomib. The nanosystem was designed to enhance the proteasome inhibitor activity in pancreatic cell lines, S2-013 and hTERT-HPNE. The hydrodynamic diameter of chitosan-gum arabic-gold nanoparticles loaded with bortezomib is around 330 nm. Laser scanning confocal microscopy images show the uptake of the gold nanoparticle/bortezomib encapsulated in chitosan-gum arabic matrix and the fast internalization of these nano combinations into pancreatic cells. Cytotoxic assays assessed that positively charged nanosystems reduce the cell growth and cell proliferation of S2-013s, but the same effect was not observed in cytotoxic response in hTERT-HPNE cells. The outcomes of this study demonstrate the capacity of chitosan-gum arabic nanocarriers to deliver gold nanoparticles/anticancer drug and to increase the permeation and retention effect in S2-013 cells and minimize drug side effects in HPNE cells.

Stimulus-responsive zinc oxide-functionalized macromolecular humic acid nanocarrier for enhancement of antibacterial activity of ciprofloxacin hydrochloride.

PubMed

Murugesan, Gowri; Latha, Nachimuthu; Suganya, Kannan; Murugan, Marudhamuthu; Munusamy, Murugan A; Rajan, Mariappan

2018-07-15

Macromolecular of naturally occurring humic acid (HA) have garnered interest in the chemical, biological and medicine industry owing to their unique behavior, i.e., strong adsorptive and non-toxic nature. Here, we investigated the functionalization of organic (HA) with inorganic (ZnO) hybrid nanoparticles for topical and site-targeted delivery of ciprofloxacin by simple emulsification techniques. Ciprofloxacin (CIPRO)-encapsulated hybrid nanocarrier constitute an attractive novel drug delivery vehicle for sustained release of antibiotics to bacterial infection sites in an extended and controlled manner. The analytical characteristics of the designed system were thoroughly investigated by FTIR, XRD, SEM/EDAX, and TEM. The drug release of ciprofloxacin over 24h was 87.5%, 98.03%, 97.44%, and 97.24% for pH2.5, 5.5, 6.8, and 8.0, respectively. The antibacterial activities results confirmed that the CIPRO-encapsulated hybrid nanocarrier showed excellent growth inhibition against microorganisms. This hybrid nanocarrier loaded with antibiotics represents a promising approach for targeted and controlled drug delivery to infected sites. Copyright © 2018 Elsevier B.V. All rights reserved.

Sniffing out the truth: clinical diagnosis using the electronic nose.

PubMed

Pavlou, A K; Turner, A P

2000-02-01

Recently the use of smell in clinical diagnosis has been rediscovered due to major advances in odour sensing technology and artificial intelligence (AI). It was well known in the past that a number of infectious or metabolic diseases could liberate specific odours characteristic of the disease stage. Later chromatographic techniques identified an enormous number of volatiles in human clinical specimens that might serve as potential disease markers. "Artificial nose" technology has been employed in several areas of medical diagnosis, including rapid detection of tuberculosis (TB), Helicobacter pylori (HP) and urinary tract infections (UTI). Preliminary results have demonstrated the possibility of identifying and characterising microbial pathogens in clinical specimens. A hybrid intelligent model of four interdependent "tools", odour generation "kits", rapid volatile delivery and recovery systems, consistent low drift sensor performance and a hybrid intelligent system of parallel neural networks (NN) and expert systems, have been applied in gastric, pulmonary and urine diagnosis. Initial clinical tests have shown that it may be possible in the near future to use electronic nose technology not only for the rapid detection of diseases such as peptic ulceration, UTI, and TB but also for the continuous dynamic monitoring of disease stages. Major advances in information and gas sensor technology could enhance the diagnostic power of future bio-electronic noses and facilitate global surveillance models of disease control and management.

Nasalization by Nasalis larvatus: Larger noses audiovisually advertise conspecifics in proboscis monkeys.

PubMed

Koda, Hiroki; Murai, Tadahiro; Tuuga, Augustine; Goossens, Benoit; Nathan, Senthilvel K S S; Stark, Danica J; Ramirez, Diana A R; Sha, John C M; Osman, Ismon; Sipangkui, Rosa; Seino, Satoru; Matsuda, Ikki

2018-02-01

Male proboscis monkeys have uniquely enlarged noses that are prominent adornments, which may have evolved through their sexually competitive harem group social system. Nevertheless, the ecological roles of the signals encoded by enlarged noses remain unclear. We found significant correlations among nose, body, and testis sizes and a clear link between nose size and number of harem females. Therefore, there is evidence supporting both male-male competition and female choice as causal factors in the evolution of enlarged male noses. We also observed that nasal enlargement systematically modifies the resonance properties of male vocalizations, which probably encode male quality. Our results indicate that the audiovisual contributions of enlarged male noses serve as advertisements to females in their mate selection. This is the first primate research to evaluate the evolutionary processes involved in linking morphology, acoustics, and socioecology with unique masculine characteristics.

Nasalization by Nasalis larvatus: Larger noses audiovisually advertise conspecifics in proboscis monkeys

PubMed Central

Koda, Hiroki; Murai, Tadahiro; Tuuga, Augustine; Goossens, Benoit; Nathan, Senthilvel K.S.S.; Stark, Danica J.; Ramirez, Diana A. R.; Sha, John C. M.; Osman, Ismon; Sipangkui, Rosa; Seino, Satoru; Matsuda, Ikki

2018-01-01

Male proboscis monkeys have uniquely enlarged noses that are prominent adornments, which may have evolved through their sexually competitive harem group social system. Nevertheless, the ecological roles of the signals encoded by enlarged noses remain unclear. We found significant correlations among nose, body, and testis sizes and a clear link between nose size and number of harem females. Therefore, there is evidence supporting both male-male competition and female choice as causal factors in the evolution of enlarged male noses. We also observed that nasal enlargement systematically modifies the resonance properties of male vocalizations, which probably encode male quality. Our results indicate that the audiovisual contributions of enlarged male noses serve as advertisements to females in their mate selection. This is the first primate research to evaluate the evolutionary processes involved in linking morphology, acoustics, and socioecology with unique masculine characteristics. PMID:29507881

Correcting the short nose in revision rhinoplasty.

PubMed

Toriumi, Dean M; Patel, Amit B; DeRosa, Jaimie

2006-11-01

The scope of this article is directed toward strategic planning and surgical treatment of the postoperative short nose deformity. Emphasis is placed on controlled repositioning of the central compartment of the nose (tip and columella), followed by moving the nostrils back into a more natural position with the use of autologous grafting techniques. The overall goal is to achieve the desired esthetic transformation while maximizing nasal function with good long-term results.