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1.
Mar Drugs ; 19(2)2021 Feb 02.
Article in English | MEDLINE | ID: mdl-33540717

ABSTRACT

For tissue engineering applications, biodegradable scaffolds containing high molecular weights (MW) of collagen and sodium alginate have been developed and characterized. However, the properties of low MW collagen-based scaffolds have not been studied in previous research. This work examined the distinctive properties of low MW collagen-based scaffolds with alginate unmodified and modified by subcritical water. Besides, we developed a facile method to cross-link water-soluble scaffolds using glutaraldehyde in an aqueous ethanol solution. The prepared cross-linked scaffolds showed good structural properties with high porosity (~93%) and high cross-linking degree (50-60%). Compared with collagen (6000 Da)-based scaffolds, collagen (25,000 Da)-based scaffolds exhibited higher stability against collagenase degradation and lower weight loss in phosphate buffer pH 7.4. Collagen (25,000 Da)-based scaffolds with modified alginate tended to improve antioxidant capacity compared with scaffolds containing unmodified alginate. Interestingly, in vitro coagulant activity assay demonstrated that collagen (25,000 Da)-based scaffolds with modified alginate (C25-A63 and C25-A21) significantly reduced the clotting time of human plasma compared with scaffolds consisting of unmodified alginate. Although some further investigations need to be done, collagen (25,000 Da)-based scaffolds with modified alginate should be considered as a potential candidate for tissue engineering applications.


Subject(s)
Alginates/chemistry , Biocompatible Materials/chemistry , Collagen/chemistry , Tissue Engineering/methods , Tissue Scaffolds/chemistry , Alginates/pharmacology , Biocompatible Materials/pharmacology , Blood Coagulation/drug effects , Blood Coagulation/physiology , Chemical Phenomena/drug effects , Collagen/pharmacology , Humans , Molecular Weight , Spectroscopy, Fourier Transform Infrared/methods , Tensile Strength/drug effects , Tensile Strength/physiology
2.
Biomacromolecules ; 21(2): 725-731, 2020 02 10.
Article in English | MEDLINE | ID: mdl-31869220

ABSTRACT

In biomedicine, PEGylation is one of the most successful strategies to modify the physicochemical and biological properties of peptides, proteins, and other biomacromolecules. Because of the polydisperse nature of regular PEGs and limited PEGylation strategies, it is challenging to quantitatively fine-tune and accurately predict the properties of biomacromolecules after PEGylation. However, such fine-tuning and prediction may be crucial for their biomedical applications. Herein, some monodisperse PEGylation strategies, including backbone PEGylation, side-chain PEGylation, and highly branched PEGylation, have been developed. In a comparative fashion, the impact of PEGylation strategies and monodisperse PEG sizes on the physicochemical and biological properties, including lipophilicity, thermosensitivity, biocompatibility, plasma stability, and drug delivery capability, of peptidic polymers has been quantitatively studied. It was found that the physicochemical and biological properties of PEGylated peptidic polymers can be quantitatively fine-tuned and accurately predicted through these monodisperse PEGylation strategies. After the comparative study, a side-chain monodisperse PEGylated peptidic polymer was chosen as fluorine-19 magnetic resonance and fluorescence dual-imaging traceable drug delivery vehicle. Our study may not only promote the transformation of PEGylation from an empirical technology to a quantitative science but also shed light on the rational design of PEGylated biomaterials and pharmaceutics.


Subject(s)
Biocompatible Materials/chemistry , Biocompatible Materials/metabolism , Chemical Phenomena/drug effects , Polyethylene Glycols/chemistry , Polyethylene Glycols/metabolism , Biocompatible Materials/pharmacology , Cell Survival/drug effects , Cell Survival/physiology , Dose-Response Relationship, Drug , Hep G2 Cells , Humans , Magnetic Resonance Spectroscopy/methods , Polyethylene Glycols/pharmacology , Polymers/chemistry , Polymers/metabolism , Polymers/pharmacology
3.
Drug Dev Ind Pharm ; 46(5): 717-731, 2020 May.
Article in English | MEDLINE | ID: mdl-32249604

ABSTRACT

Objectives: l-Glutathione (GSH) is an endogenous tripeptide with super antioxidant properties. In this study, preformulation parameters of GSH and its degradation products were fully investigated.Significance: To date, no experimental preformulation data is available for GSH. Therefore, to the author's knowledge, this is the first study to experimentally determine the preformulation parameters of GSH, which can be considered more reliable for further studies.Methods: An HPLC method for GSH was optimized and validated to accurately quantify the GSH amount in solution, used to investigate GSH's solubility and Log P. Differential Scanning Calorimeter and Thermogravimetric Analyzer were used to evaluate the thermal properties of GSH. Polarized microscope and Fourier-transform Infrared Spectroscopy were used to determine GSH's crystal habits and functional groups, respectively. Forced degradation kinetics and the degradation products were investigated and identified by LC-MS, respectively. GSH's cellular cytotoxicity on fibroblasts was investigated by MTT assay.Results: It was determined that GSH has high aqueous solubility (252.7 mg/mL), low Log P (-3.1), a melting endotherm of 195 °C and decomposition at 210°C, negligible moisture content, and a rectangular/cylindrical-shaped crystalline form. Seven degradation products were identified; one of the major degradation products of GSH under different conditions is first order kinetic oxidation into glutathione disulfide. No cytotoxicity was observed when fibroblasts were treated with GSH (0.005-10.000 mg/mL).Conclusions: Precise preformulation parameters of GSH were obtained, and these are imperative for the development and optimization of advanced GSH formulations.


Subject(s)
Chemistry, Pharmaceutical/methods , Cytotoxins/chemistry , Cytotoxins/toxicity , Glutathione/chemistry , Glutathione/toxicity , Cell Survival/drug effects , Cell Survival/physiology , Cells, Cultured , Chemical Phenomena/drug effects , Cytotoxins/analysis , Dose-Response Relationship, Drug , Drug Compounding/methods , Fibroblasts/drug effects , Fibroblasts/pathology , Glutathione/analysis , Humans , Kinetics , Tandem Mass Spectrometry/methods , X-Ray Diffraction/methods
4.
Appl Microbiol Biotechnol ; 103(15): 6369-6383, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31203419

ABSTRACT

The different impacts, especially on soil physicochemical and microbial characteristics, among disinfestation methods based on different principles (including physical, chemical, and biological) have not been illustrated well. Here, we used steam sterilization, dazomet fumigation, and reductive soil disinfestation (RSD) methods representative of physical, chemical, and biological soil disinfestation, respectively, to disinfest seriously degraded greenhouse soils before watermelon cultivation in one season. Compared with the control, RSD significantly decreased the soil nitrate content by 85.9% and the electrical conductivity by 52.0% and increased the soil pH to 7.44. Although all three soil disinfestations significantly decreased the abundance of the pathogen Fusarium oxysporum by 83.0-99.2%, their impacts on soil microbial characteristics were variable. Briefly, steam sterilization significantly changed multiple bacterial and fungal properties. Dazomet fumigation impacted mainly fungal properties, such as abundance, diversity, and community structure, but RSD significantly decreased bacterial diversity and altered the bacterial community structure. Although the differences mentioned above got smaller after watermelon cultivation, the plant performances differed dramatically in different soils. The largest plant biomass, fruit ratio, and yield were found in the RSD-treated soil, whereas the lowest fruit ratio and yield were found in the steam-sterilized soil. The soil nitrate content, electrical conductivity, bacterial diversity and community structure, and some specific microbial agents, such as Aspergillus, Cladosporium, and Pseudomonas, were correlated with plant performance. RSD is a promising soil disinfestation strategy to support plant growth in intensively cultivated greenhouse soils with serious problems, such as acidification, salinization, and pathogen accumulation.


Subject(s)
Biota/drug effects , Biota/radiation effects , Disinfection/methods , Pest Control/methods , Soil Microbiology , Anti-Infective Agents/pharmacology , Chemical Phenomena/drug effects , Chemical Phenomena/radiation effects , Fruit/growth & development , Fumigation , Hot Temperature , Soil/chemistry , Steam , Thiadiazines/pharmacology
5.
Pharm Dev Technol ; 23(10): 1047-1056, 2018 Dec.
Article in English | MEDLINE | ID: mdl-28368215

ABSTRACT

Clove is an aromatic plant spice with potent antioxidant and anti-inflammatory activity. Eugenol is the main compound which contributes to such medicinal and nutritional benefits. To date, the formulation of unstable, volatile and poorly water-soluble compounds remains a challenging task. Lipid formulations can be used to improve physicochemical and biopharmaceutical properties of poorly soluble compounds. The aim of this study is to investigate the effects of lipids, such as Gelucire and Compritol on physicochemical properties; stability and in vitro intestinal permeation of spray dried powdered formulations loaded with clove's bioactive compounds. Results showed that eugenol retention in spray-dried powders could be correlated with antioxidant activity and with mass recovery after spray drying. Adding Gelucire but not Compritol to clove extract formulations, improved solubility of spray dried powders. Stability test in high humidity environment (63.5% RH) suggested that formulations including both Gelucire and Compritol were significantly more stable compared to the formulation without any lipid at the two tested temperatures (25 °C and 40 °C). This suggests that lipid additions to clove (Syzygium aromaticum) extract formulations provide protective effects for the spray dried powders in high-humidity environments. In addition, results from in vitro intestinal permeation studies suggested that eugenol uptake, was not being hindered by transporters nor was the absorption being affected by lipid formulations.


Subject(s)
Fats/chemistry , Fats/pharmacokinetics , Gastrointestinal Absorption/drug effects , Oils/chemistry , Oils/pharmacokinetics , Plant Extracts/chemistry , Plant Extracts/pharmacokinetics , Syzygium , Caco-2 Cells , Chemical Phenomena/drug effects , Drug Compounding/methods , Drug Stability , Drug Storage/standards , Excipients/chemistry , Excipients/pharmacokinetics , Humans , Plant Components, Aerial , Plant Extracts/isolation & purification , Powders
6.
Article in English | MEDLINE | ID: mdl-29985754

ABSTRACT

Water quality of Douro and Ave lower basin was evaluated regarding physicochemical parameters (pH, conductivity, dissolved oxygen and temperature), nutrient compounds (nitrates, nitrites, ammonium and orthophosphates), chlorophyll a and occurrence of trace elements (Li, Be, Al, Ti, V, Cr, Co, Ni, Cu, Zn, Se, Mo, Ag, Cd, Sb, Ba, Tl, Pb, Th and U). To study spatiotemporal variations and possible anthropogenic sources, estuarine samples were collected at nine sampling sites in Douro and five in Ave distributed along the estuaries at four sampling campaigns (spring, summer, fall and winter). According to the water quality standards for aquatic life and recreation, Douro and Ave river water quality was found out of safe limits regarding several parameters. Nitrate levels were systematically high (> 50 mg L-1 in a significant number of samples) and mean levels of trace elements were higher than the established values of Canadian Environmental Quality Guidelines for aquatic life protection for Al, Cu, Se, Ag, Cd and Pb in Douro and Ave, and also Zn in Ave. Significant spatial differences were found in Ave river estuary for trace elements with a clear trend for higher values from upstream to downstream found. Seasonal differences were also observed particularly in Douro river estuary with higher levels in spring for most elements.


Subject(s)
Chemical Phenomena , Rivers/chemistry , Trace Elements/analysis , Water Pollutants, Chemical/analysis , Water Quality , Chemical Phenomena/drug effects , Environmental Monitoring/methods , Estuaries , Fresh Water/chemistry , Humans , Portugal , Seasons , Time Factors , Trace Elements/pharmacokinetics , Water Pollutants, Chemical/pharmacokinetics
7.
World J Microbiol Biotechnol ; 34(2): 25, 2018 Jan 12.
Article in English | MEDLINE | ID: mdl-29330693

ABSTRACT

Brewery effluent (BE) as an appreciable and sustainable resource presented new possibilities in low-cost algal biomass production, whereas the relatively low essential macronutrients hindered extensive applications as growth medium for microalgae cultivation. The objective of this study was to investigate the feasibility of an integrated treatment strategy initiated by BE coupling phytohormones in augmenting biomass and lipid accumulation in Coccomyxa subellipsoidea. Results revealed that BE coupling synthetic 1-naphthaleneacetic acid (NAA) accomplished the favorable lipid productivity of 481.76 mg/L/days, representing 6.80- to 9.71-fold more than that of single BE as well as standard Basal media. BE coupling NAA feeding also heightened the proportions of C16-C18 fatty acids (over 96%) and mono-unsaturated C18:1 (approximate 45%) which were prone to high-quality biofuels-making. Such profound lipids accumulation might be attributable to that BE coupling NAA treatment drove most of metabolic flux (i.e. acetyl-CoA) derived from TCA cycle and glycolysis flowing into lipid accumulation pathway. Concurrently, the complete removal of total nitrogen and total phosphorus by C. subellipsoidea with assistance of NAA were easily complied with the permissible dischargeable limits for BE. These present results strongly demonstrated that BE coupling NAA was a potential feeding strategy in boosting algal lipid productivity and further provided great possibilities in linking affordable algal biomass production with high-efficient biological contaminants removal.


Subject(s)
Biomass , Chlorophyta/growth & development , Chlorophyta/metabolism , Lipids/biosynthesis , Plant Growth Regulators/pharmacology , Biofuels , Biosynthetic Pathways/drug effects , Chemical Phenomena/drug effects , Culture Media/metabolism , Fatty Acids/biosynthesis , Lipid Metabolism/drug effects , Microalgae/growth & development , Microalgae/metabolism , Naphthaleneacetic Acids/metabolism , Nitrogen/metabolism , Phosphorus/metabolism
8.
AAPS PharmSciTech ; 18(8): 2936-2948, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28432615

ABSTRACT

A revolutionary paradigm shift is being observed currently, towards the use of therapeutic biologics for disease management. The present research was focused on designing an efficient dosage form for transdermal delivery of α-choriogonadotropin (high molecular weight biologic), through biodegradable polymeric microneedles. Polyvinylpyrrolidone-based biodegradable microneedle arrays loaded with high molecular weight polypeptide, α-choriogonadotropin, were fabricated for its systemic delivery via transdermal route. Varied process and formulation parameters were optimized for fabricating microneedle array, which in turn was expected to temporally rupture the stratum corneum layer of the skin, acting as a major barrier to drug delivery through transdermal route. The developed polymeric microneedles were optimized on the basis of quality attributes like mechanical strength, axial strength, insertion ratio, and insertion force analysis. The optimized polymeric microneedle arrays were characterized for in vitro drug release studies, ex vivo drug permeation studies, skin resealing studies, and in vivo pharmacokinetic studies. Results depicted that fabricated polymeric microneedle arrays with mechanical strength of above 5 N and good insertion ratio exhibited similar systemic bioavailability of α-choriogonadotropin in comparison to marketed subcutaneous injection formulation of α-choriogonadotropin. Thus, it was ultimately concluded that the designed drug delivery system can serve as an efficient tool for systemic delivery of therapeutic biologics, with an added benefit of overcoming the limitations of parenteral delivery, achieving better patient acceptability and compliance.


Subject(s)
Drug Evaluation, Preclinical/methods , Microinjections/standards , Needles/standards , Polymers/metabolism , Skin Absorption/drug effects , Administration, Cutaneous , Animals , Chemical Phenomena/drug effects , Drug Delivery Systems/methods , Drug Delivery Systems/standards , Epidermis/drug effects , Epidermis/metabolism , Injections, Subcutaneous , Microinjections/methods , Molecular Weight , Organ Culture Techniques , Polymers/administration & dosage , Polymers/chemistry , Rats , Rats, Sprague-Dawley , Skin/drug effects , Skin/metabolism , Skin Absorption/physiology , Transdermal Patch/standards
9.
Pharm Res ; 33(8): 1881-98, 2016 08.
Article in English | MEDLINE | ID: mdl-27075873

ABSTRACT

PURPOSE: To develop vincristine (VCR) and doxorubicin (DOX) co-encapsulated thermo-sensitive liposomes (VD-TSL) against drug resistance, with increased tumor inhibition rate and decreased system toxicity, improving drug targeting efficiency upon mild hyperthermia (HT) in solid tumor. METHODS: Based on similar physicochemical properties, VCR and DOX were co-loaded in TSL with pH gradient active loading method and characterized. The time-dependent drug release profiles at 37 and 42°C were assessed by HPLC. Then we analysed the phospholipids in filtrate after ultrafiltration and studied VD-TSL stability in mimic in vivo conditions and long-time storage conditions (4°C and -20°C). Cytotoxic effect was studied on PANC and sw-620 using MTT. Intracellular drug delivery was studied by confocal microscopy on HT-1080. In vivo imaging of TSL pharmacokinetic and biodistribution was performed on MCF-7 tumor-bearing nude mice. And therapeutic efficacy on these xenograft models were followed under HT. RESULTS: VD-TSL had excellent particle distribution (about 90 nm), high entrapment efficiency (>95%), obvious thermo-sensitive property, and good stability. MTT proved VD-TSL had strongest cell lethality compared with other formulations. Confocal microscopy demonstrated specific accumulation of drugs in tumor cells. In vivo imaging proved the targeting efficiency of TSL under hyperthermia. Then therapeutic efficacy revealed synergism of VCR and DOX co-loaded in TSL, together with HT. CONCLUSION: VD-TSL could increase drug efficacy and decrease system toxicity, by making good use of synergism of VCR and DOX, as well as high targeting efficiency of TSL.


Subject(s)
Antibiotics, Antineoplastic/administration & dosage , Doxorubicin/administration & dosage , Drug Carriers/administration & dosage , Drug Delivery Systems/methods , Vincristine/administration & dosage , Animals , Antibiotics, Antineoplastic/chemistry , Breast Neoplasms/drug therapy , Chemical Phenomena/drug effects , Doxorubicin/chemistry , Drug Carriers/chemistry , Drug Synergism , Female , Humans , Liposomes , MCF-7 Cells , Mice , Mice, Nude , Temperature , Tissue Distribution/drug effects , Tissue Distribution/physiology , Vincristine/chemistry , Xenograft Model Antitumor Assays/methods
10.
Pharm Dev Technol ; 21(5): 519-27, 2016 Aug.
Article in English | MEDLINE | ID: mdl-25757641

ABSTRACT

The combined properties of SepineoP 600 (S600), a self-gelling dispersion and SepineoSE 68 (M68), a natural liquid crystal forming surfactant, were utilized in the development of emulgel base for topical application. The emulgels were prepared in water alone or combined with propylene glycol (PG), polyethylene glycol 400 (PEG400) and glycerol (G) as cosolvents. Emulgels were characterized for their optical and flow behavior. Two model drugs: caffeine (CF) and methylparaben (MP) were used in the evaluation of drug permeation across the stratum corneum (SC). The results showed that emulgel prepared using 70% PG:water (1:1) and 30% S600 has the best flow behavior compared to other cosolvents. Also the permeability coefficient of CF was found to be higher than that of MP and the addition of 3% M68 improved the physical stability of the emulgel, but it did not affect the drug diffusion profile.


Subject(s)
Skin Absorption/physiology , Solvents/chemistry , Solvents/metabolism , Surface-Active Agents/chemistry , Surface-Active Agents/metabolism , Chemical Phenomena/drug effects , Chemistry, Pharmaceutical , Female , Gels , Humans , Organ Culture Techniques , Skin Absorption/drug effects , Solvents/pharmacology , Surface-Active Agents/pharmacology
11.
Infect Immun ; 83(1): 292-9, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25368115

ABSTRACT

Shigella spp. are causative agents of bacillary dysentery, a human illness with high global morbidity levels, particularly among elderly and infant populations. Shigella infects via the fecal-oral route, and its virulence is dependent upon a type III secretion system (T3SS). Two components of the exposed needle tip complex of the Shigella T3SS, invasion plasmid antigen D (IpaD) and IpaB, have been identified as broadly protective antigens in the mouse lethal pneumonia model. A recombinant fusion protein (DB fusion) was created by joining the coding sequences of IpaD and IpaB. The DB fusion is coexpressed with IpaB's cognate chaperone, IpgC, for proper recombinant expression. The chaperone can then be removed by using the mild detergents octyl oligooxyethelene (OPOE) or N,N-dimethyldodecylamine N-oxide (LDAO). The DB fusion in OPOE or LDAO was used for biophysical characterization and subsequent construction of an empirical phase diagram (EPD). The EPD showed that the DB fusion in OPOE is most stable at neutral pH below 55 °C. In contrast, the DB fusion in LDAO exhibited remarkable thermal plasticity, since this detergent prevents the loss of secondary and tertiary structures after thermal unfolding at 90 °C, as well as preventing thermally induced aggregation. Moreover, the DB fusion in LDAO induced higher interleukin-17 secretion and provided a higher protective efficacy in a mouse challenge model than did the DB fusion in OPOE. These data indicate that LDAO might introduce plasticity to the protein, promoting thermal resilience and enhanced protective efficacy, which may be important in its use as a subunit vaccine.


Subject(s)
Antigens, Bacterial/chemistry , Antigens, Bacterial/immunology , Bacterial Proteins/chemistry , Bacterial Proteins/immunology , Bacterial Vaccines/chemistry , Bacterial Vaccines/immunology , Detergents/chemistry , Animals , Chemical Phenomena/drug effects , Hydrogen-Ion Concentration , Mice , Protein Stability , Recombinant Fusion Proteins/chemistry , Recombinant Fusion Proteins/immunology , Temperature
12.
Drug Dev Ind Pharm ; 41(12): 1997-2005, 2015.
Article in English | MEDLINE | ID: mdl-25835068

ABSTRACT

The purpose of this paper was to study the influence of drug physicochemical characteristics on in vitro transdermal absorption of hydrophobic drug nanosuspensions. Four drug nanosuspensions were produced by high-pressure homogenization technique, which were the same in stabilizer and similar in particle size. Differential scanning calorimetry and powder X-ray diffraction analysis showed that the crystalline state of the nanocrystals did not change. In vitro permeation study demonstrated that the drug nanosuspensions have a higher rate of permeation that ranged from 1.69- to 3.74-fold compared to drug microsuspensions. Correlation analysis between drug physicochemical properties and Jss revealed that log P and pKa were factors that influenced the in vitro transdermal absorption of hydrophobic drug nanosuspensions, and drugs with a log P value around 3 and a higher pKa value (when pKa < pH+2) would gain higher Jss in this paper.


Subject(s)
Chemical Phenomena , Hydrophobic and Hydrophilic Interactions , Nanoparticles/chemistry , Nanoparticles/metabolism , Skin Absorption/physiology , Administration, Cutaneous , Animals , Chemical Phenomena/drug effects , Hydrophobic and Hydrophilic Interactions/drug effects , Male , Nanoparticles/administration & dosage , Organ Culture Techniques , Particle Size , Rats , Rats, Sprague-Dawley , Skin Absorption/drug effects , X-Ray Diffraction
13.
Small ; 10(3): 566-75, 417, 2014 Feb 12.
Article in English | MEDLINE | ID: mdl-24038954

ABSTRACT

A major drawback with current cancer therapy is the prevalence of unrequired dose-limiting toxicity to non-cancerous tissues and organs, which is further compounded by a limited ability to rapidly and easily monitor drug delivery, pharmacodynamics and therapeutic response. In this report, the design and characterization of novel multifunctional "theranostic" nanoparticles (TNPs) is described for enzyme-specific drug activation at tumor sites and simultaneous in vivo magnetic resonance imaging (MRI) of drug delivery. TNPs are synthesized by conjugation of FDA-approved iron oxide nanoparticles ferumoxytol to an MMP-activatable peptide conjugate of azademethylcolchicine (ICT), creating CLIO-ICTs (TNPs). Significant cell death is observed in TNP-treated MMP-14 positive MMTV-PyMT breast cancer cells in vitro, but not MMP-14 negative fibroblasts or cells treated with ferumoxytol alone. Intravenous administration of TNPs to MMTV-PyMT tumor-bearing mice and subsequent MRI demonstrates significant tumor selective accumulation of the TNP, an observation confirmed by histopathology. Treatment with CLIO-ICTs induces a significant antitumor effect and tumor necrosis, a response not observed with ferumoxytol. Furthermore, no toxicity or cell death is observed in normal tissues following treatment with CLIO-ICTs, ICT, or ferumoxytol. These findings demonstrate proof of concept for a new nanotemplate that integrates tumor specificity, drug delivery and in vivo imaging into a single TNP entity through attachment of enzyme-activated prodrugs onto magnetic nanoparticles. This novel approach holds the potential to significantly improve targeted cancer therapies, and ultimately enable personalized therapy regimens.


Subject(s)
Magnetic Resonance Imaging , Matrix Metalloproteinases, Membrane-Associated/metabolism , Nanoparticles , Neoplasms/diagnosis , Neoplasms/therapy , Animals , Antineoplastic Agents/pharmacology , Caspases/metabolism , Chemical Phenomena/drug effects , Female , Fibroblasts/drug effects , Fibroblasts/enzymology , Fibroblasts/pathology , Humans , Mice
14.
Environ Sci Technol ; 47(8): 3883-92, 2013 Apr 16.
Article in English | MEDLINE | ID: mdl-23458316

ABSTRACT

Nanotechnology has vast potential for expanded development and novel application in numerous sectors of society. With growing use and applications, substantial production volumes and associated environmental release can be anticipated. Exposure effect of nanoparticles (NP) on biological systems may be intrinsic to their physicochemical properties introducing unknown associated risk. Herein, we expand the knowledge of health and environmental impact of silver nanoparticles (AgNPs), testing the acute toxicity of 14 AgNP preparations on developing zebrafish embryos (Danio rerio). Toxicological end points, including mortality, hatching rate, and heart rate were recorded. Concentration, stabilization agent and physicochemical properties were monitored as contributing outcome factors. Our findings indicate wide ranging LC50 24 h postfertilization values (0.487 ppm (0.315, 0.744 95% CI) to 47.89 ppm (18.45, 203.49 95% CI)), and indicate surface charge and ionic dissolution as key contributory factors in AgNP exposure outcome.


Subject(s)
Chemical Phenomena/drug effects , Environmental Exposure/analysis , Metal Nanoparticles/toxicity , Silver/toxicity , Toxicity Tests, Acute , Zebrafish/metabolism , Animals , Chorion/drug effects , Chorion/embryology , Embryo, Nonmammalian/drug effects , Embryo, Nonmammalian/physiology , Heart Rate/drug effects , Larva/drug effects , Light , Metal Nanoparticles/ultrastructure , Movement/drug effects , Scattering, Radiation , Static Electricity , Survival Analysis , Zebrafish/embryology
15.
J Mater Sci Mater Med ; 24(2): 437-45, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23160913

ABSTRACT

Hydroxyapatite (HA) is a synthetic biomaterial and has been found to promote new bone formation when implanted in a bone defect site. However, its use is often limited due to its slow osteointegration rate and low antibacterial activity, particularly where HA has to be used for long term biomedical applications. This work will describe the synthesis and detailed characterization of zinc-substituted HA (ZnHA) as an alternative biomaterial to HA. ZnHA containing 1.6 wt% Zn was synthesized via a co-precipitation reaction between calcium hydroxide, orthophosphoric acid and zinc nitrate hexahydrate. Single-phase ZnHA particles with a rod-like morphology measuring ~50 nm in length and ~15 nm in width, were obtained and characterized using transmission electron microscopy and X-ray diffraction. The substitution of Zn into HA resulted in a decrease in both the a- and c-axes of the unit cell parameters, thereby causing the HA crystal structure to alter. In vitro cell culture work showed that ZnHA possessed enhanced bioactivity since an increase in the growth of human adipose-derived mesenchymal stem cells along with the bone cell differentiation markers, were observed. In addition, antibacterial work demonstrated that ZnHA exhibited antimicrobial capability since there was a significant decrease in the number of viable Staphylococcus aureus bacteria after in contact with ZnHA.


Subject(s)
Anti-Bacterial Agents , Biocompatible Materials/pharmacology , Durapatite/chemistry , Zinc/chemistry , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Biocompatible Materials/chemical synthesis , Biocompatible Materials/chemistry , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Cells, Cultured , Chemical Phenomena/drug effects , Durapatite/chemical synthesis , Durapatite/pharmacology , Humans , Materials Testing , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/physiology , Microbial Sensitivity Tests , Microbial Viability/drug effects , Microscopy, Electron, Scanning , Microscopy, Electron, Transmission , Staphylococcus aureus/drug effects , Staphylococcus aureus/growth & development , Staphylococcus aureus/physiology
16.
Small ; 8(21): 3289-99, 2012 Nov 05.
Article in English | MEDLINE | ID: mdl-22837153

ABSTRACT

The primary aim of these interdisciplinary studies is to investigate the effect of surface carbon coating on the physico-chemical properties and toxicity of carbon-coated and noncoated copper and nickel nanoparticles (C-Cu, Cu, C-Ni, Ni NPs) in A549 alveolar epithelial cells. Compared to Cu NPs, C-Cu NPs exhibit protection against surface oxidation, tenfold higher cellular uptake, and fourfold lower release of soluble Cu. The toxicity of C-Cu NPs and Cu NPs is associated with pronounced damage to mitochondrial function and plasma membrane integrity, respectively. Compared to Cu and C-Cu NPs, Ni and C-Ni NPs are less toxic. These studies demonstrate that correlations can be drawn between physico-chemical properties and resultant toxicity of NPs as a function of surface carbon coating.


Subject(s)
Carbon/chemistry , Chemical Phenomena/drug effects , Copper/toxicity , Metal Nanoparticles/toxicity , Nickel/toxicity , Cell Line, Tumor , Cell Membrane/drug effects , Cell Membrane/metabolism , Copper/metabolism , Dimerization , Ethidium/metabolism , Fluoresceins/metabolism , Humans , Intracellular Membranes/drug effects , Intracellular Membranes/metabolism , Lysosomes/drug effects , Lysosomes/metabolism , Metal Nanoparticles/ultrastructure , Mitochondria/drug effects , Mitochondria/metabolism , Nickel/metabolism , Particle Size , Photoelectron Spectroscopy , Solubility , Static Electricity , Thermodynamics
17.
J Bone Miner Metab ; 30(2): 154-63, 2012 Mar.
Article in English | MEDLINE | ID: mdl-21947781

ABSTRACT

Bone deformities caused by the chronic intake of large quantities of fluoride and the beneficial effect of calcium on its control have been studied for many years, but only limited data are available on the quantitative effect of fluoride intake and the beneficial impact of calcium on fluoride-induced changes in bone at the molecular level. It is necessary to determine the degree of fluoride-induced changes in bone at different levels of fluoride intake to evaluate the optimum safe intake level of fluoride for maintaining bone health and quality. The ameliorative effect of calcium at different dose levels on minimizing fluoride-induced changes in bone is important to quantify the amount of calcium intake necessary for reducing fluoride toxicity. Thirty rabbits, 2 months old, were divided into five groups. Group I animals received 1 mg/l fluoride and 0.11% calcium diet; groups II and III received 10 mg/l fluoride and diet with 0.11% or 2.11% calcium, respectively; and groups IV and V received 150 mg/l fluoride and diet with 2.11% or 0.11% calcium, respectively. Analysis of bone density, ash content, fluoride, calcium, phosphorus, and Ca:P molar ratio levels after 6 months of treatment indicated that animals that received high fluoride with low-calcium diet showed significant detrimental changes in physicochemical properties of bone. Animals that received fluoride with high calcium intake showed notable amelioration of the impact of calcium on fluoride-induced changes in bone. The degree of fluoride-induced characteristic changes in structural properties such as crystalline size, crystallinity, and crystallographic "c"-axis length of bone apatite cells was also assessed by X-ray diffraction and Fourier transform infrared studies. X-ray images showed bone deformity changes such as transverse stress growth lines, soft tissue ossification, and calcification in different parts of bones as a result of high fluoride accumulation and the beneficial role of calcium intake on its control.


Subject(s)
Bone and Bones/chemistry , Bone and Bones/drug effects , Calcium/pharmacology , Chemical Phenomena/drug effects , Fluorides/pharmacology , Animals , Bone and Bones/diagnostic imaging , Crystallization , Fluorides/metabolism , Male , Rabbits , Radiography , Spectroscopy, Fourier Transform Infrared , X-Ray Diffraction
18.
Environ Sci Technol ; 46(1): 10-8, 2012 Jan 03.
Article in English | MEDLINE | ID: mdl-21786750

ABSTRACT

Structural analogues are assumed to elicit toxicity via similar predominant modes of action (MOAs). Currently, MOA categorization of chemicals in environmental risk assessment is mainly based on the physicochemical properties of potential toxicants. It is often not known whether such classification schemes are also supported by mechanistic biological data. In this study, the toxic effects of two groups of structural analogues (alcohols and anilines) with predefined MOA (narcotics and polar narcotics) were investigated at different levels of biological organization (gene transcription, energy reserves, and growth). Chemical similarity was not indicative of a comparable degree of toxicity and a similar biological response. Categorization of the test chemicals based on the different biological responses (growth, energy use, and gene transcription) did not result in a classification of the predefined narcotics versus the predefined polar narcotics. Moreover, gene transcription based clustering profiles were indicative of the observed effects at higher level of biological organization. Furthermore, a small set of classifier genes could be identified that was discriminative for the clustering pattern. These classifier genes covaried with the organismal and physiological responses. Compared to the physico-chemistry based MOA classification, integrated biological multilevel effect assessment can provide the necessary MOA information that is crucial in high-quality environmental risk assessment. Our findings support the view that transcriptomics tools hold considerable promise to be used in biological response based mechanistic profiling of potential (eco)toxicants.


Subject(s)
Chemical Phenomena/drug effects , Daphnia/genetics , Daphnia/physiology , Environmental Exposure/analysis , Narcotics/chemistry , Narcotics/pharmacology , Animals , Cluster Analysis , Daphnia/drug effects , Daphnia/growth & development , Energy Metabolism/drug effects , Gene Expression Profiling , Least-Squares Analysis , RNA, Messenger/genetics , RNA, Messenger/metabolism , Transcription, Genetic/drug effects
19.
Int J Mol Sci ; 14(1): 457-69, 2012 Dec 24.
Article in English | MEDLINE | ID: mdl-23263673

ABSTRACT

Electrochemically activated solutions (ECAS) are generated by electrolysis of NaCl solutions, and demonstrate broad spectrum antimicrobial activity and high environmental compatibility. The biocidal efficacy of ECAS at the point of production is widely reported in the literature, as are its credentials as a "green biocide." Acidic ECAS are considered most effective as biocides at the point of production and ill suited for extended storage. Acidic ECAS samples were stored at 4 °C and 20 °C in glass and polystyrene containers for 398 days, and tested for free chlorine, pH, ORP and bactericidal activity throughout. ORP and free chlorine (mg/L) in stored ECAS declined over time, declining at the fastest rate when stored at 20 °C in polystyrene and at the slowest rate when stored at 4 °C in glass. Bactericidal efficacy was also affected by storage and ECAS failed to produce a 5 log(10) reduction on five occasions when stored at 20 °C. pH remained stable throughout the storage period. This study represents the longest storage evaluation of the physiochemical parameters and bactericidal efficacy of acidic ECAS within the published literature and reveals that acidic ECAS retain useful bactericidal activity for in excess of 12 months, widening potential applications.


Subject(s)
Anti-Bacterial Agents/pharmacology , Chemical Phenomena/drug effects , Drug Storage , Electrochemistry , Chlorine/analysis , Hydrogen-Ion Concentration , Microbial Sensitivity Tests , Microbial Viability/drug effects , Oxidation-Reduction/drug effects , Pseudomonas aeruginosa/drug effects , Solutions , Time Factors
20.
Int J Biol Macromol ; 196: 63-71, 2022 Jan 31.
Article in English | MEDLINE | ID: mdl-34896473

ABSTRACT

This study aimed to investigate the effect of atmospheric pressure non-thermal pin-to-plate plasma on the functional, rheological, thermal, and morphological properties of mango seed kernel starch. As cold plasma contains highly reactive species and free radicals, it is expected to cause noticeable modifications in the attributes of starch treated. The isolated mango seed kernel starch was subjected to the plasma treatment of input voltages 170 and 230 V for 15 and 30 min of exposure. Water adsorption, swelling, and solubility at lower temperatures. There has been a significant reduction (p < 0.05) in pH values of starch from 7.09 to 6.16 and also the desirable reduction in turbidity values by 42.60%. However, there has been no significant change in the oil and water binding behavior of the starch. The FTIR spectra of MSKS demonstrate the formation of amines which contributes to the better hydrophilic nature of the starch. The structural modification has been adequately confirmed by SEM images. The maximum voltage and time combination, lead to depolymerization of starch which is supported by NMR spectra thus affecting thermal and rheological properties. The application of cold plasma-modified MSKS in food would facilitate stable and smooth textural development.


Subject(s)
Chemical Phenomena/drug effects , Mangifera/chemistry , Plasma Gases/chemistry , Plasma Gases/pharmacology , Rheology/drug effects , Seeds/chemistry , Starch/chemistry , Spectrum Analysis , Starch/isolation & purification
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