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Sample records for release protein-loaded nanoparticles

  1. Preparation, characterization and in-vitro evaluation of sustained release protein-loaded nanoparticles based on biodegradable polymers

    PubMed Central

    Mukherjee, Biswajit; Santra, Kousik; Pattnaik, Gurudutta; Ghosh, Soma

    2008-01-01

    Controlled drug delivery technology of proteins/peptides from biodegradable nanoparticles has emerged as one of the eminent areas to overcome formulation associated problems of the macromolecules. The purpose of the present investigation was to develop protein-loaded nanoparticles using biodegradable polymer poly l-lactide-co-glycolidic acid (PLGA) with bovine serum albumin (BSA) as a model protein. Despite many studies available with PLGA-based protein-loaded nanoparticles, production know-how, process parameters, protein loading, duration of protein release, narrowing polydispersity of particles have not been investigated enough to scale up manufacturing of protein-loaded nanoparticles in formulations. Different process parameters such as protein/polymer ratio, homogenizing speed during emulsifications, particle surface morphology and surface charges, particle size analysis and in-vitro protein release were investigated. The in-vitro protein release study suggests that release profile of BSA from nanoparticles could be modulated by changing protein-polymer ratios and/or by varying homogenizing speed during multiple-emulsion preparation technique. The formulation prepared with protein-polymer ratio of 1:60 at 17,500 rpm gave maximum protein-loading, minimum polydispersion with maximally sustained protein release pattern, among the prepared formulations. Decreased (10,000 rpm) or enhanced (24,000 rpm) homogenizing speeds resulted in increased polydispersion with larger particles having no better protein-loading and -release profiles in the present study. PMID:19337417

  2. Impact of PEG and PEG-b-PAGE modified PLGA on nanoparticle formation, protein loading and release.

    PubMed

    Rietscher, René; Czaplewska, Justyna A; Majdanski, Tobias C; Gottschaldt, Michael; Schubert, Ulrich S; Schneider, Marc; Lehr, Claus-Michael

    2016-03-16

    The effect of modifying the well-established pharmaceutical polymer PLGA by different PEG-containing block-copolymers on the preparation of ovalbumin (OVA) loaded PLGA nanoparticles (NPs) was studied. The used polymers contained poly(d,l-lactic-co-glycolic acid) (PLGA), polyethylene glycol (PEG) and poly(allyl glycidyl ether) (PAGE) as building blocks. The double emulsion technique yielded spherical NPs in the size range from 170 to 220 nm (PDI<0.15) for all the differently modified polymers, allowing to directly compare protein loading of and release. PEGylation is usually believed to increase the hydrophilic character of produced particles, favoring encapsulation of hydrophilic substances. However, in this study simple PEGylation of PLGA had only a slight effect on protein release. In contrast, incorporating a PAGE block between the PEG and PLGA units, also eventually enabling active targeting introducing a reactive group, led to a significantly higher loading (+25%) and release rate (+100%), compared to PLGA and PEG-b-PLGA NPs. PMID:26784983

  3. Biodegradable nanoparticles for protein delivery: analysis of preparation conditions on particle morphology and protein loading, activity and sustained release properties.

    PubMed

    Coleman, Jason; Lowman, Anthony

    2012-01-01

    PLGA particles have been extensively used as a sustained drug-delivery system, but there are multiple drawbacks when delivering proteins. The focus of this work is to address the most significant disadvantages to the W/O/W double emulsion procedure and demonstrate that simple changes to this procedure can have significant changes to particle size and dispersity and considerable improvements to protein loading, activity and sustained active protein release. A systematic approach was taken to analyze the effects of the following variables: solvent miscibility (dichloromethane (DCM), ethyl acetate, acetone), homogenization speed (10 000-25 000 rpm), PLGA concentration (10-30 mg/ml) and additives in both the organic (sucrose acetate isobutyrate (SAIB)) and aqueous (bovine serum albumin (BSA)) phases. Increasing solvent miscibility decreased particle size, dispersity and protein denaturation, while maintaining adequate protein loading. Increasing solvent miscibility also lowered the impact of homogenization on particle size and dispersity and protein activity. Changes to PLGA concentration demonstrated a minimum impact on particle size and dispersity, but showed an inverse relationship between protein encapsulation efficiency and particle protein weight percent. Most particles tested provided sustained release of active protein over 60 days. Increasing solvent miscibility resulted in increases in the percent of active protein released. When subjected to synthesis conditions with DCM as the solvent, BSA as a stabilizer resulted in the maximum stabilization of protein at a concentration of 100 mg/ml. At this concentration, BSA allowed for increases in the total amount of active protein delivered for all three solvents. The benefit of SAIB was primarily increased protein loading.

  4. Spectral and spatial characterization of protein loaded PLGA nanoparticles.

    PubMed

    Zidan, Ahmed S; Rahman, Ziyaur; Habib, Muhammad J; Khan, Mansoor A

    2010-03-01

    The objective of this study was to evaluate near infrared (NIR) spectroscopy and imaging as approaches to assess drug contents in poly(dl-lactide-co-glycolide) (PLGA) based nanoparticles of a model protein, cyclosporine A (CyA). A 6-factors 12-runs designed set of experiments with Plackett-Burman (PB) screening was applied in order to examine the effects of drug loading (X(1)), polymer loading (X(2)), emulsifier concentration (X(3)), stirring rate (X(4)), type of organic solvent (X(5)), and ratio of organic to aqueous phases' volumes (X(6)), on drug entrapment efficiency (EFF). After omitting the factors with nonsignificant influences on EFF, a reduced mathematical relationship, EFF = 48.34 + 7.3X(1) - 29.95X(3), was obtained to explain the effect of the significant factors on EFF. Using two different sets for calibration and validation, the developed NIR calibration model was able to assess CyA contents within the 12 PB formulations. NIR spectral imaging was capable of clearly distinguishing the 12 formulations, both qualitatively and quantitatively. A good correlation with a coefficient of 0.9727 was obtained for constructing a quantile-quantile plot for the actual drug loading percentage and the % standard deviation obtained for the drug loading prediction using the hyperspectral images. PMID:19774658

  5. A New Strategy Based on Smrho Protein Loaded Chitosan Nanoparticles as a Candidate Oral Vaccine against Schistosomiasis

    PubMed Central

    Oliveira, Carolina R.; Rezende, Cíntia M. F.; Silva, Marina R.; Pêgo, Ana Paula; Borges, Olga; Goes, Alfredo M.

    2012-01-01

    Background Schistosomiasis is one of the most important neglected tropical diseases and an effective control is unlikely in the absence of improved sanitation and vaccination. A new approach of oral vaccination with alginate coated chitosan nanoparticles appears interesting because their great stability and the ease of target accessibility, besides of chitosan and alginate immunostimulatory properties. Here we propose a candidate vaccine based on the combination of chitosan-based nanoparticles containing the antigen SmRho and coated with sodium alginate. Methods and Findings Our results showed an efficient performance of protein loading of nanoparticles before and after coating with alginate. Characterization of the resulting nanoparticles reported a size around 430 nm and a negative zeta potential. In vitro release studies of protein showed great stability of coated nanoparticles in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). Further in vivo studies was performed with different formulations of chitosan nanoparticles and it showed that oral immunization was not able to induce high levels of antibodies, otherwise intramuscular immunization induced high levels of both subtypes IgG1 and IgG2a SmRho specific antibodies. Mice immunized with nanoparticles associated to CpG showed significant modulation of granuloma reaction. Mice from all groups immunized orally with nanoparticles presented significant levels of protection against infection challenge with S. mansoni worms, suggesting an important role of chitosan in inducing a protective immune response. Finally, mice immunized with nanoparticles associated with the antigen SmRho plus CpG had 38% of the granuloma area reduced and also presented 48% of protection against of S. mansoni infection. Conclusions Taken together, this results support this new strategy as an efficient delivery system and a potential vaccine against schistosomiasis. PMID:23209848

  6. Controlled release behaviour of protein-loaded microparticles prepared via coaxial or emulsion electrospray

    PubMed Central

    Wang, Ying; Yang, Xiaoping; Liu, Wentao; Zhang, Feng; Cai, Qing; Deng, Xuliang

    2013-01-01

    Biodegradable poly (lactic-co-glycolic acid) (PLGA) microparticles are an effective way to achieve sustained drug release. In this study, we investigated a sustained release model of PLGA microparticles with incorporated protein via either emulsion or coaxial electrospray techniques. PLGA (75:25) was used as the carrier, and bovine serum albumin as a model protein. Coaxial electrospray resulted in a type of core–shell structure with mean diameters of 2.41 ± 0.60 µm and a centralised protein distribution within the core. Emulsion electrospray formed bigger microparticles with mean diameters of 22.75 ± 8.05 µm and a heterogeneous protein distribution throughout the microparticles. The coaxial electrospray microparticles presented a much slighter burst release than the emulsion electrospray microparticles. Loading efficiency was significantly higher (p < 0.05) in the coaxial group than emulsion group. This indicated that both emulsion and coaxial electrospray could produce protein-loaded microparticles with sustained release behaviour, but the former revealed a superior approach for drug delivery. PMID:23346923

  7. Understanding the quality of protein loaded PLGA nanoparticles variability by Plackett-Burman design.

    PubMed

    Rahman, Ziyaur; Zidan, Ahmed S; Habib, Muhammad J; Khan, Mansoor A

    2010-04-15

    The aim of this investigation was to screen and understand the product variability due to important factors affecting the characteristics CyA-PLGA nanoparticles prepared by O/W emulsification-solvent evaporation method. Independent variables studied were cyclosporine A (CyA) (X(1)), PLGA (X(2)), and emulsifier concentration namely SLS (X(3)), stirring rate (X(4)), type of organic solvent employed (chloroform or dichloromethane, X(5)) and organic to aqueous phase ratio (X(6)). The nanoparticles properties considered were encapsulation efficiency (Y(1)), mean particle size (Y(2)), zeta potential (Y(3)), burst effect (Y(4)) and dissolution efficiency (Y(5)). The statistical analysis of the results allowed determining the most influent factors. The nanoparticles were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray powder diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. The factors combination showed variability of entrapment efficiency (Y(1)), mean particle size (Y(2)) and zeta potential (Y(3)) from 10.17% to 93.01%, 41.60 to 372.80 nm and 29.60 to 34.90 mV, respectively. Initially, nanoparticles showed burst effect followed by sustained release during the 7-day in vitro release study period. The dissolution efficiency (Y(5)) varied from 52.67% to 84.11%. The nanoparticles revealed Higuchi release pattern and release occurred by coupling of diffusion and erosion. In conclusion, this study revealed the potential of QbD in understanding the effect of formulation and process variables on the characteristics on CyA-PLGA nanoparticles.

  8. Co-encapsulation of lyoprotectants improves the stability of protein-loaded PLGA nanoparticles upon lyophilization.

    PubMed

    Fonte, Pedro; Araújo, Francisca; Seabra, Vítor; Reis, Salette; van de Weert, Marco; Sarmento, Bruno

    2015-12-30

    The purpose of this work was to evaluate the influence of the co-encapsulation of lyoprotectants with insulin into PLGA nanoparticles, on the stability of the protein and nanoparticles upon lyophilization. Different lyoprotectants were used, namely trehalose, glucose, sucrose, fructose and sorbitol at 10% (w/v). Insulin-loaded PLGA nanoparticles with co-encapsulated lyoprotectants achieved a mean particle size of 386-466nm, and a zeta potential ranging between -34 and -38mV, dependent on the lyoprotectant used. Formulations had association efficiencies and loading capacities of 85-91% and 10-12%, respectively. The lyophilization process increased the colloidal stability of nanoparticles, and maintained their spherical shape and smooth surface, particularly in presence of lyoprotectants. XRPD revealed that the lyophilizates of nanoparticles with co-encapsulated lyoprotectants were amorphous, whereas formulations with externally added lyoprotectants, except trehalose, showed crystallinity. FTIR assessment showed that co-encapsulating lyoprotectants better preserved insulin structure upon lyophilization with a spectral area overlap of 82-87%, compared to only 72% in lyoprotectant absence. These results were confirmed by circular dichroism spectroscopy. Surprisingly, the simultaneous co-encapsulation and addition of lyoprotectants was detrimental to protein stabilization. The insulin in vitro release studies demonstrated that formulations with co-encapsulated trehalose, glucose, sucrose, fructose and sorbitol achieved 83%, 69%, 70%, 77% and 74%, respectively after 48h. In contrast, formulations added with those lyoprotectants prior lyophilization showed a lower release rate not higher than 60% after 48h. This work gives rise to a different promising strategy of co-encapsulating lyoprotectants and therapeutic proteins, to better stabilize protein structure upon lyophilization.

  9. Biodegradable polymersomes with an ionizable membrane: facile preparation, superior protein loading, and endosomal pH-responsive protein release.

    PubMed

    Li, Shaoke; Meng, Fenghua; Wang, Zhongjuan; Zhong, Yinan; Zheng, Meng; Liu, Haiyan; Zhong, Zhiyuan

    2012-09-01

    Novel biodegradable polymersomes containing an ionizable membrane were developed for efficient loading and rapid intracellular release of proteins. The polymersomes were prepared from poly(ethylene glycol)-b-poly(trimethylene carbonate) (PEG-PTMC) block copolymer derivatives containing acrylate, carboxylic acid, and amine groups along PTMC block, which are denoted as PEG-PTMC(AC), PEG-PTMC(COOH), and PEG-PTMC(NH(2)), respectively. Notably, nano-sized polymersomes (95.1-111.6nm) were formed by directly dispersing these copolymers in phosphate buffer at room temperature. Both FITC-labeled bovine serum albumin (FITC-BSA) and cytochrome C (FITC-CC) were readily loaded into PEG-PTMC(COOH) and PEG-PTMC(NH(2)) polymersomes with remarkably high loading levels. Interestingly, in vitro release studies showed that PEG-PTMC(COOH) and PEG-PTMC(NH(2)) polymersomes had pH-responsive protein release behaviors in which significantly faster protein release was observed at endosomal pH than at physiological pH. MTT assays indicated that these polymersomes had low cytotoxicity. Furthermore, confocal laser scanning microscope (CLSM) observations revealed that FITC-CC loaded polymersomes efficiently delivered proteins into MCF-7 cells following 24h incubation. Importantly, flow cytometry showed that CC-loaded polymersomes induced markedly enhanced apoptosis in MCF-7 cells as compared to free CC. These novel membrane ionizable biodegradable polymersomes have appeared as highly promising nanocarriers for efficient intracellular protein delivery.

  10. Nanoparticle release from dental composites.

    PubMed

    Van Landuyt, K L; Hellack, B; Van Meerbeek, B; Peumans, M; Hoet, P; Wiemann, M; Kuhlbusch, T A J; Asbach, C

    2014-01-01

    Dental composites typically contain high amounts (up to 60 vol.%) of nanosized filler particles. There is a current concern that dental personnel (and patients) may inhale nanosized dust particles (<100 nm) during abrasive procedures to shape, finish or remove restorations but, so far, whether airborne nanoparticles are released has never been investigated. In this study, composite dust was analyzed in real work conditions. Exposure measurements of dust in a dental clinic revealed high peak concentrations of nanoparticles in the breathing zone of both dentist and patient, especially during aesthetic treatments or treatments of worn teeth with composite build-ups. Further laboratory assessment confirmed that all tested composites released very high concentrations of airborne particles in the nanorange (>10(6)cm(-3)). The median diameter of airborne composite dust varied between 38 and 70 nm. Electron microscopic and energy dispersive X-ray analysis confirmed that the airborne particles originated from the composite, and revealed that the dust particles consisted of filler particles or resin or both. Though composite dust exhibited no significant oxidative reactivity, more toxicological research is needed. To conclude, on manipulation with the bur, dental composites release high concentrations of nanoparticles that may enter deeply into the lungs.

  11. Controlled drug release from hydrogel nanoparticle networks.

    PubMed

    Huang, Gang; Gao, Jun; Hu, Zhibing; St John, John V; Ponder, Bill C; Moro, Dan

    2004-02-10

    Monodisperse nanoparticles of poly-N-isopropylacrylamide-co-allylamine (PNIPAM-co-allylamine) and PNIPAM-co-acrylic acid (PNIPAM-co-AA) were synthesized. The close-packed PNIPAM-co-allylamine and PNIPAM-co-AA nanoparticles were converted to three-dimensional gel networks by covalently crosslinking neighboring particles at room temperature and neutral pH using glutaric dialdehyde and adipic acid dihydrazide, respectively. Controlled release studies were conducted using dextran markers of various molecular weights as model macromolecular drugs. Release was quantified under various physical conditions, including a range of temperatures and dextran molecular weights. Dextran, entrapped in cavities in the nanoparticle network, was released with a rate regulated by their molecular weights and cavity size. No release from a conventional bulk PNIPAM gel, with high crosslinking density, was observed. The rate of release from the PNIPAM-co-allylamine network was temperature-dependent, being much faster at room temperature than that at human body temperature. In contrast, release of low molecular weight dextrans from the PNIPAM-co-AA network showed a temperature-independent release profile. These nanoparticle networks have several advantages over conventional bulk gels for controlling the release of high molecular weight biomolecules. PMID:14744482

  12. Electrosprayed nanoparticle delivery system for controlled release.

    PubMed

    Eltayeb, Megdi; Stride, Eleanor; Edirisinghe, Mohan; Harker, Anthony

    2016-09-01

    This study utilises an electrohydrodynamic technique to prepare core-shell lipid nanoparticles with a tunable size and high active ingredient loading capacity, encapsulation efficiency and controlled release. Using stearic acid and ethylvanillin as model shell and active ingredients respectively, we identify the processing conditions and ratios of lipid:ethylvanillin required to form nanoparticles. Nanoparticles with a mean size ranging from 60 to 70nm at the rate of 1.37×10(9) nanoparticles per minute were prepared with different lipid:ethylvanillin ratios. The polydispersity index was ≈21% and the encapsulation efficiency ≈70%. It was found that the rate of ethylvanillin release was a function of the nanoparticle size, and lipid:ethylvanillin ratio. The internal structure of the lipid nanoparticles was studied by transmission electron microscopy which confirmed that the ethylvanillin was encapsulated within a stearic acid shell. Fourier transform infrared spectroscopy analysis indicated that the ethylvanillin had not been affected. Extensive analysis of the release of ethylvanillin was performed using several existing models and a new diffusive release model incorporating a tanh function. The results were consistent with a core-shell structure. PMID:27207047

  13. Proretinal nanoparticles: stability, release, efficacy, and irritation.

    PubMed

    Pisetpackdeekul, Pimolphan; Supmuang, Piyapan; Pan-In, Porntip; Banlunara, Wijit; Limcharoen, Benchaphorn; Kokpol, Chayada; Wanichwecharungruang, Supason

    2016-01-01

    Despite many potent biological activities, retinoids such as retinoic acid (RA) and retinal possess dose-related broad side effects. In this study, we show that this problem, which has been unsolvable for a long time, can be tackled through a controlled release strategy in which retinal is continuously delivered to the skin via sustained release from proretinal nanoparticles. The water dispersible proretinal nanoparticles are stable when kept in water at neutral pH and at room temperature for 8 months under light-proof conditions, and show sustained release of retinal into human synthetic sebum at a pH of 5. In the daily topical application tests performed for 4 weeks on rats' skin, the nanoparticles showed superior ability to increase epidermal thickness compared to RA and retinal, with no skin irritation observed for the proretinal particles, but severe skin irritation observed for RA and free retinal. When tested under occlusion conditions in human volunteers, insignificant skin irritation was observed for the proretinal nanoparticles. The 12-week, double-blind, split-face study on human volunteers indicates better antiaging efficacy of the particles as compared to the free RA. PMID:27499622

  14. Proretinal nanoparticles: stability, release, efficacy, and irritation

    PubMed Central

    Pisetpackdeekul, Pimolphan; Supmuang, Piyapan; Pan-In, Porntip; Banlunara, Wijit; Limcharoen, Benchaphorn; Kokpol, Chayada; Wanichwecharungruang, Supason

    2016-01-01

    Despite many potent biological activities, retinoids such as retinoic acid (RA) and retinal possess dose-related broad side effects. In this study, we show that this problem, which has been unsolvable for a long time, can be tackled through a controlled release strategy in which retinal is continuously delivered to the skin via sustained release from proretinal nanoparticles. The water dispersible proretinal nanoparticles are stable when kept in water at neutral pH and at room temperature for 8 months under light-proof conditions, and show sustained release of retinal into human synthetic sebum at a pH of 5. In the daily topical application tests performed for 4 weeks on rats’ skin, the nanoparticles showed superior ability to increase epidermal thickness compared to RA and retinal, with no skin irritation observed for the proretinal particles, but severe skin irritation observed for RA and free retinal. When tested under occlusion conditions in human volunteers, insignificant skin irritation was observed for the proretinal nanoparticles. The 12-week, double-blind, split-face study on human volunteers indicates better antiaging efficacy of the particles as compared to the free RA. PMID:27499622

  15. Chitosan-based nanoparticles as a sustained protein release carrier for tissue engineering applications.

    PubMed

    Hou, Yaping; Hu, Junli; Park, Hyejin; Lee, Min

    2012-04-01

    Chitosan/tripolyphosphate/chondroitin sulfate (Chi/TPP/CS) nanoparticles were prepared by an ionic gelation method to obtain a controlled release of proteins. Using Nel-like molecule-1 (Nell-1), a novel osteogenic protein, as a model protein, it was demonstrated that adjusting the composition of the particles modulated the protein association and release kinetics of incorporated proteins. Increasing the amounts of Chi crosslinking agents, TPP and CS, in the particles achieved sustained protein release. An increase in crosslinking density decreased degradation rates of the particles. Furthermore, the bioactivity of the protein was preserved during the encapsulating procedure into the particles. To demonstrate the feasibility of Chi/TPP/CS nanoparticles as sustained release carriers for tissue engineering scaffold applications, protein-loaded nanoparticles were successfully incorporated into collagen hydrogels or prefabricated porous poly(lactide-co-glycolide) (PLGA) scaffolds without obstructing the integrity of the hydrogels or porous structure of the scaffolds. Thus, we expect that these particles have a potential for efficient protein carriers in tissue engineering applications, and will be further evaluated in vivo. PMID:22275184

  16. Nitric oxide-releasing porous silicon nanoparticles.

    PubMed

    Kafshgari, Morteza Hasanzadeh; Cavallaro, Alex; Delalat, Bahman; Harding, Frances J; McInnes, Steven Jp; Mäkilä, Ermei; Salonen, Jarno; Vasilev, Krasimir; Voelcker, Nicolas H

    2014-01-01

    In this study, the ability of porous silicon nanoparticles (PSi NPs) to entrap and deliver nitric oxide (NO) as an effective antibacterial agent is tested against different Gram-positive and Gram-negative bacteria. NO was entrapped inside PSi NPs functionalized by means of the thermal hydrocarbonization (THC) process. Subsequent reduction of nitrite in the presence of d-glucose led to the production of large NO payloads without reducing the biocompatibility of the PSi NPs with mammalian cells. The resulting PSi NPs demonstrated sustained release of NO and showed remarkable antibacterial efficiency and anti-biofilm-forming properties. These results will set the stage to develop antimicrobial nanoparticle formulations for applications in chronic wound treatment.

  17. Nitric oxide-releasing porous silicon nanoparticles

    NASA Astrophysics Data System (ADS)

    Kafshgari, Morteza Hasanzadeh; Cavallaro, Alex; Delalat, Bahman; Harding, Frances J.; McInnes, Steven JP; Mäkilä, Ermei; Salonen, Jarno; Vasilev, Krasimir; Voelcker, Nicolas H.

    2014-07-01

    In this study, the ability of porous silicon nanoparticles (PSi NPs) to entrap and deliver nitric oxide (NO) as an effective antibacterial agent is tested against different Gram-positive and Gram-negative bacteria. NO was entrapped inside PSi NPs functionalized by means of the thermal hydrocarbonization (THC) process. Subsequent reduction of nitrite in the presence of d-glucose led to the production of large NO payloads without reducing the biocompatibility of the PSi NPs with mammalian cells. The resulting PSi NPs demonstrated sustained release of NO and showed remarkable antibacterial efficiency and anti-biofilm-forming properties. These results will set the stage to develop antimicrobial nanoparticle formulations for applications in chronic wound treatment.

  18. Nitric oxide-releasing porous silicon nanoparticles

    PubMed Central

    2014-01-01

    In this study, the ability of porous silicon nanoparticles (PSi NPs) to entrap and deliver nitric oxide (NO) as an effective antibacterial agent is tested against different Gram-positive and Gram-negative bacteria. NO was entrapped inside PSi NPs functionalized by means of the thermal hydrocarbonization (THC) process. Subsequent reduction of nitrite in the presence of d-glucose led to the production of large NO payloads without reducing the biocompatibility of the PSi NPs with mammalian cells. The resulting PSi NPs demonstrated sustained release of NO and showed remarkable antibacterial efficiency and anti-biofilm-forming properties. These results will set the stage to develop antimicrobial nanoparticle formulations for applications in chronic wound treatment. PMID:25114633

  19. Combinatorial Synthesis of and high-throughput protein release from polymer film and nanoparticle libraries.

    PubMed

    Petersen, Latrisha K; Chavez-Santoscoy, Ana V; Narasimhan, Balaji

    2012-09-06

    Polyanhydrides are a class of biomaterials with excellent biocompatibility and drug delivery capabilities. While they have been studied extensively with conventional one-sample-at-a-time synthesis techniques, a more recent high-throughput approach has been developed enabling the synthesis and testing of large libraries of polyanhydrides(1). This will facilitate more efficient optimization and design process of these biomaterials for drug and vaccine delivery applications. The method in this work describes the combinatorial synthesis of biodegradable polyanhydride film and nanoparticle libraries and the high-throughput detection of protein release from these libraries. In this robotically operated method (Figure 1), linear actuators and syringe pumps are controlled by LabVIEW, which enables a hands-free automated protocol, eliminating user error. Furthermore, this method enables the rapid fabrication of micro-scale polymer libraries, reducing the batch size while resulting in the creation of multivariant polymer systems. This combinatorial approach to polymer synthesis facilitates the synthesis of up to 15 different polymers in an equivalent amount of time it would take to synthesize one polymer conventionally. In addition, the combinatorial polymer library can be fabricated into blank or protein-loaded geometries including films or nanoparticles upon dissolution of the polymer library in a solvent and precipitation into a non-solvent (for nanoparticles) or by vacuum drying (for films). Upon loading a fluorochrome-conjugated protein into the polymer libraries, protein release kinetics can be assessed at high-throughput using a fluorescence-based detection method (Figures 2 and 3) as described previously(1). This combinatorial platform has been validated with conventional methods(2) and the polyanhydride film and nanoparticle libraries have been characterized with (1)H NMR and FTIR. The libraries have been screened for protein release kinetics, stability and

  20. Sustained release Curcumin loaded Solid Lipid Nanoparticles

    PubMed Central

    Jourghanian, Parisa; Ghaffari, Solmaz; Ardjmand, Mehdi; Haghighat, Setareh; Mohammadnejad, Mahdieh

    2016-01-01

    Purpose: curcumin is poorly water soluble drug with low bioavailability. Use of lipid systems in lipophilic substances increases solubility and bioavailability of poorly soluble drugs. The aim of this study was to prepare curcumin loaded Solid Lipid Nanoparticles (SLNs) with high loading efficiency, small particle size and prolonged release profile with enhanced antibacterial efficacy. Methods: to synthesize stable SLNs, freeze- Drying was done using mannitol as cryoprotectant. Cholesterol was used as carrier because of good tolerability and biocompatibility. SLNs were prepared using high pressure homogenization method. Results: optimized SLNs had 112 and 163 nm particle size before and after freeze drying, respectively. The prepared SLNs had 71% loading efficiency. 90% of loaded curcumin was released after 48 hours. Morphologic study for formulation was done by taking SEM pictures of curcumin SLNs. Results show the spherical shape of curcumin SLNs. DSC studies were performed to determine prolonged release mechanism. Antimicrobial studies were done to compare the antimicrobial efficacy of curcumin SLNs with free curcumin. DSC studies showed probability of formation of hydrogen bonds between cholesterol and curcumin which resulted in prolonged release of curcumin. Lipid structure of cholesterol could cause enhanced permeability in studied bacteria to increase antibacterial characteristics of curcumin. Conclusion: the designed curcumin SLNs could be candidate for formulation of different dosage forms or cosmeceutical products. PMID:27123413

  1. Polymer-coated echogenic lipid nanoparticles with dual release triggers.

    PubMed

    Nahire, Rahul; Haldar, Manas K; Paul, Shirshendu; Mergoum, Anaas; Ambre, Avinash H; Katti, Kalpana S; Gange, Kara N; Srivastava, D K; Sarkar, Kausik; Mallik, Sanku

    2013-03-11

    Although lipid nanoparticles are promising drug delivery vehicles, passive release of encapsulated contents at the target site is often slow. Herein, we report contents release from targeted, polymer-coated, echogenic lipid nanoparticles in the cell cytoplasm by redox trigger and simultaneously enhanced by diagnostic frequency ultrasound. The lipid nanoparticles were polymerized on the external leaflet using a disulfide cross-linker. In the presence of cytosolic concentrations of glutathione, the lipid nanoparticles released 76% of encapsulated contents. Plasma concentrations of glutathione failed to release the encapsulated contents. Application of 3 MHz ultrasound for 2 min simultaneously with the reducing agent enhanced the release to 96%. Folic acid conjugated, doxorubicin-loaded nanoparticles showed enhanced uptake and higher cytotoxicity in cancer cells overexpressing the folate receptor (compared to the control). With further developments, these lipid nanoparticles have the potential to be used as multimodal nanocarriers for simultaneous targeted drug delivery and ultrasound imaging.

  2. Release, transport and toxicity of engineered nanoparticles.

    PubMed

    Soni, Deepika; Naoghare, Pravin K; Saravanadevi, Sivanesan; Pandey, Ram Avatar

    2015-01-01

    Recent developments in nanotechnology have facilitated the synthesis of novel engineered nanoparticles (ENPs) that possess new and different physicochemical properties. These ENPs have been ex tensive ly used in various commercial sectors to achieve both social and economic benefits. However. the increasing production and consumption of ENPs by many different industries has raised concerns about their possible release and accumulation in the environment. Released EN Ps may either remain suspended in the atmosphere for several years or may accumulate and eventually be modified int o other substances. Settled nanoparticles can he easily washed away during ra in s. and therefore may easily enter the food chain via water and so il. Thus. EN Ps can contaminate air. water and soil and can subsequently pose adverse risks to the health of different organisms. Studies to date indicate that ENP transport to and within the ecosystem depend on their chemical and physical properties (viz .. size. shape and solubility) . Therefore. the EN Ps display variable behavior in the environment because of their individual properties th at affect their tendency for adsorption, absorption, diffusional and colloidal interaction. The transport of EN Ps also influences their fate and chemical transformation in ecosystems. The adsorption, absorption and colloidal interaction of ENPs affect their capacity to be degraded or transformed, whereas the tendency of ENPs to agglomerate fosters their sedimentation. How widely ENPs are transported and their environmental fate influence how tox ic they may become to environmental organisms. One barrier to fully understanding how EN Ps are transformed in the environment and how best to characterize their toxicity, is related to the nature of their ultrafine structure. Experiments with different animals, pl ants, and cell lines have revealed that ENPs induce toxicity via several cellular pathways that is linked to the size. shape. surface area

  3. Nanoparticle-triggered release from lipid membrane vesicles.

    PubMed

    Reimhult, Erik

    2015-12-25

    Superparamagnetic iron oxide nanoparticles are used in a rapidly expanding number of research and practical applications in biotechnology and biomedicine. We highlight how recent developments in iron oxide nanoparticle design and understanding of nanoparticle membrane interactions have led to applications in magnetically triggered, liposome delivery vehicles with controlled structure. Nanoscale vesicles actuated by incorporated nanoparticles allow for controlling location and timing of compound release, which enables e.g. use of more potent drugs in drug delivery as the interaction with the right target is ensured. This review emphasizes recent results on the connection between nanoparticle design, vesicle assembly and the stability and release properties of the vesicles. While focused on lipid vesicles magnetically actuated through iron oxide nanoparticles, these insights are of general interest for the design of capsule and cell delivery systems for biotechnology controlled by nanoparticles.

  4. Assembly of Bio-Nanoparticles for Double Controlled Drug Release

    PubMed Central

    Huang, Wei; Zhang, Jianfei; Dorn, Harry C.; Zhang, Chenming

    2013-01-01

    A critical limiting factor of chemotherapy is the unacceptably high toxicity. The use of nanoparticle based drug carriers has significantly reduced the side effects and facilitated the delivery of drugs. Source of the remaining side effect includes (1) the broad final in vivo distribution of the administrated nanoparticles, and (2) strong basal drug release from nanoparticles before they could reach the tumor. Despite the advances in pH-triggered release, undesirable basal drug release has been a constant challenge under in vivo conditions. In this study, functionalized single walled carbon nanohorn supported immunoliposomes were assembled for paclitaxel delivery. The immunoliposomes were formulated with polyethylene glycol, thermal stable and pH sensitive phospholipids. Each nanohorn was found to be encapsulated within one immunoliposome. Results showed a highly pH dependent release of paclitaxel in the presence of serum at body temperature with minimal basal release under physiological conditions. Upon acidification, paclitaxel was released at a steady rate over 30 days with a cumulative release of 90% of the loaded drug. The drug release results proved our hypothesized double controlled release mechanism from the nanoparticles. Other results showed the nanoparticles have doubled loading capacity compared to that of traditional liposomes and higher affinity to breast cancer cells overexpressing Her2 receptors. Internalized nanoparticles were found in lysosomes. PMID:24040316

  5. Polymeric nanoparticles containing diazepam: preparation, optimization, characterization, in-vitro drug release and release kinetic study

    NASA Astrophysics Data System (ADS)

    Bohrey, Sarvesh; Chourasiya, Vibha; Pandey, Archna

    2016-03-01

    Nanoparticles formulated from biodegradable polymers like poly(lactic-co-glycolic acid) (PLGA) are being extensively investigated as drug delivery systems due to their two important properties such as biocompatibility and controlled drug release characteristics. The aim of this work to formulated diazepam loaded PLGA nanoparticles by using emulsion solvent evaporation technique. Polyvinyl alcohol (PVA) is used as stabilizing agent. Diazepam is a benzodiazepine derivative drug, and widely used as an anticonvulsant in the treatment of various types of epilepsy, insomnia and anxiety. This work investigates the effects of some preparation variables on the size and shape of nanoparticles prepared by emulsion solvent evaporation method. These nanoparticles were characterized by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM). Zeta potential study was also performed to understand the surface charge of nanoparticles. The drug release from drug loaded nanoparticles was studied by dialysis bag method and the in vitro drug release data was also studied by various kinetic models. The results show that sonication time, polymer content, surfactant concentration, ratio of organic to aqueous phase volume, and the amount of drug have an important effect on the size of nanoparticles. Hopefully we produced spherical shape Diazepam loaded PLGA nanoparticles with a size range under 250 nm with zeta potential -23.3 mV. The in vitro drug release analysis shows sustained release of drug from nanoparticles and follow Korsmeyer-Peppas model.

  6. Mucoadhesive controlled release ciprofloxacin nanoparticles for pulmonary delivery

    NASA Astrophysics Data System (ADS)

    Mudumba, Sujata S.

    Controlled release of drugs to the lungs is an interesting and evolving field of research. The influence of physicochemical properties of nanoparticles on the controlled release of ciprofloxacin and in-vivo pharmacokinetics following pulmonary administration was evaluated. The physicochemical properties had an effect on encapsulation efficiency and surface charge, but no significant effect on particle size. The in-vitro release profiles of ciprofloxacin in phosphate buffered saline showed small differences over the range of physicochemical properties evaluated. The physicochemical properties of ciprofloxacin nanoparticles resulted in variable and unreliable nebulizer output using a vibrating mesh nebulizer whereas the impact on the aerosol properties of a jet nebulizer was negligible. Addition of mucoadhesive polymers in the nanoparticles had a three-fold increase in apparent half-life in rats by releasing ciprofloxacin over an extended release period on the surfaces of the lungs.

  7. Preparation, characterization and optimization of glipizide controlled release nanoparticles

    PubMed Central

    Emami, J.; Boushehri, M.S. Shetab; Varshosaz, J.

    2014-01-01

    The purpose of the present study was to develop glipizide controlled release nanoparticles using alginate and chitosan thorough ionotropic controlled gelation method. Glipizide is a frequently prescribed second generation sulfonylurea which lowers the blood glucose in type-two diabetics. Quick absorption of the drug from the gastrointestinal tract along with short half- life of elimination makes it a good candidate for controlled release formulations. Alginate-chitosan nanoparticles (ACNP) are convenient controlled delivery systems for glipizide, due to both the release limiting properties of the system, and the bioadhesive nature of the polymers. In the present study, glipizide loaded alginate-chitosan nanoparticles (GlACNP) were prepared, and the particle characteristics including particle size (PS), zeta potential (ZP), entrapment efficiency (EE%), loading percent (LP), and mean release time (MRT), as well as the morphology of the nanoparticles, the drug-excipient compatibility, and the release kinetics along with the drug diffusion mechanism were evaluated. The results suggested that ionotropic controlled gelation method offers the possibility of preparing the nanoparticles in mild conditions in an aqueous environment, and can lead to the preparation of particles with favorable size, controlled release characteristics, and high entrapment efficiency, serving as a convenient delivery system for glipizide. The particle and release characteristics can be efficiently optimized using the Box-Behnken design. Based on the findings of the present study, it is expected that this novel formulation be a superior therapeutic alternative to the currently available glipizide delivery systems. PMID:25657802

  8. Organically modified titania nanoparticles for sustained drug release applications.

    PubMed

    Sethi, Komal; Roy, Indrajit

    2015-10-15

    In this paper, we report the synthesis, characterization of drug-doped organically modified titania nanoparticles, and their applications in sustained drug release. The drug-doped nanoparticles were synthesized in the hydrophobic core of oil-in-water microemulsion medium. Structural aspects obtained through TEM and FESEM depicted that organically modified titania nanoparticles are monodispersed with spherical morphology, with an average size of around 200 nm. Their polymorphic forms and porosity were determined using powder XRD and BET, respectively, which showed that they are present in the anatase form, with a surface area of 136.5 m(2)/g and pore-diameter of 5.23 nm. After synthesis and basic structural characterizations, optical properties were studied for both fluorophore and drug encapsulated nanoparticles. The results showed that though the optical properties of the fluorophore are partially diminished upon nanoencapsulation, it became more stable against chemical quenching. The nanoparticles showed pH-dependent drug release pattern. In vitro studies showed that the nanoparticles were efficiently uptaken by cells. Cell viability assay results showed that though the placebo nanoparticles are non-cytotoxic, the drug-doped nanoparticles show drug-induced toxicity. Therefore, such porous nanoparticles can be used in non-toxic drug delivery applications.

  9. The controlled release of tilmicosin from silica nanoparticles.

    PubMed

    Song, Meirong; Li, Yanyan; Fai, Cailing; Cui, Shumin; Cui, Baoan

    2011-06-01

    The aim of this study was to use silica nanoparticles as the carrier for controlled release of tilmicosin. Tilmicosin was selected as a drug model molecule because it has a lengthy elimination half-life and a high concentration in milk after subcutaneous administration. Three samples of tilmicosin-loaded silica nanoparticles were prepared with different drug-loading weight. The drug-loading weight in three samples, as measured by thermal gravimetric analysis, was 29%, 42%, and 64%, respectively. With increased drug-loading weight, the average diameter of the drug-loaded silica nanoparticles was increased from 13.4 to 25.7 nm, and the zeta potential changed from-30.62 to-6.78 mV, indicating that the stability of the drug-loaded particles in the aqueous solution decreases as drug-loading weight increases. In vitro release studies in phosphate-buffered saline showed the sample with 29% drug loading had a slow and sustained drug release, reaching 44% after 72 h. The release rate rose with increased drug-loading weight; therefore, the release of tilmicosin from silica nanoparticles was well-controlled by adjusting the drug loading. Finally, kinetics analysis suggested that drug released from silica nanoparticles was mainly a diffusion-controlled process.

  10. Nitric oxide-releasing polymeric nanoparticles against Trypanosoma cruzi

    NASA Astrophysics Data System (ADS)

    Seabra, A. B.; Kitice, N. A.; Pelegrino, M. T.; Lancheros, C. A. C.; Yamauchi, L. M.; Pinge-Filho, P.; Yamada-Ogatta, S. F.

    2015-05-01

    Chagas disease, also known as American trypanosomiasis, is a potentially life-threatening illness caused by the protozoan parasite, Trypanosoma cruzi (T. cruzi), and the disease remains a major health problem in many Latin American countries. Several papers report that the killing of the parasite is dependent on the production of nitric oxide (NO). The endogenous free radical NO is an important cellular signalling molecule that plays a key role in the defense against pathogens, including T. cruzi. As T. cruzi is able to compromise host macrophages decreasing endogenous NO production, the administration of exogenous NO donors represents an interesting strategy to combat Chagas disease. Thus, the aims of this study were to prepare and evaluate the antimicrobial activity of NO-releasing polymeric nanoparticles against T. cruzi. Biocompatible polymeric nanoparticles composed of chitosan/sodium tripolyphosphate(TPP) were prepared and used to encapsulate mercaptosuccinic acid (MSA), which is a thiol-containing molecule. Nitrosation of free thiols (SH) groups of MSA were performed by the addition of equimolar amount of sodium nitrite (NaNO2), leading to the formation of S-nitroso-MSA-containing nanoparticles. These polymeric nanoparticles act as spontaneous NO donors, with free NO release. The results show the formation of nanoparticles with average hydrodynamic diameter ranging from 270 to 500 nm, average of polydispersity index of 0.35, and encapsulation efficiency in the range of 99%. The NO release kinetics from the S-nitroso-MSA-containing nanoparticles showed sustained and controlled NO release over several hours. The microbicidal activity of S-nitroso-MSA-containing nanoparticles was evaluated by incubating NO-releasing nanoparticles (200 - 600 μg/mL) with replicative and non-infective epimastigote, and non-replicative and infective trypomastigote forms of T. cruzi. In addition, a significant decrease in the percentage of macrophage-infected (with amastigotes) and

  11. pH-dependent anticancer drug release from silk nanoparticles.

    PubMed

    Seib, F Philipp; Jones, Gregory T; Rnjak-Kovacina, Jelena; Lin, Yinan; Kaplan, David L

    2013-12-01

    Silk has traditionally been used as a suture material because of its excellent mechanical properties and biocompatibility. These properties have led to the development of different silk-based material formats for tissue engineering and regenerative medicine. Although there have been a small number of studies about the use of silk particles for drug delivery, none of these studies have assessed the potential of silk to act as a stimulus-responsive anticancer nanomedicine. This report demonstrates that an acetone precipitation of silk allows the formation of uniform silk nanoparticles (98 nm diameter, polydispersity index 0.109), with an overall negative surface charge (-33.6 ± 5.8 mV), in a single step. Silk nanoparticles are readily loaded with doxorubicin (40 ng doxorubicin/μg silk) and show pH-dependent release (pH 4.5≫ 6.0 > 7.4). In vitro studies with human breast cancer cell lines demonstrates that the silk nanoparticles are not cytotoxic (IC50 > 120 μg mL(-1) ) and that doxorubicin-loaded silk nanoparticles are able to overcome drug resistance mechanisms. Live cell fluorescence microscopy studies show endocytic uptake and lysosomal accumulation of silk nanoparticles. In summary, the pH-dependent drug release and lysosomal accumulation of silk nanoparticles demonstrate the ability of drug-loaded silk nanoparticles to serve as a lysosomotropic anticancer nanomedicine.

  12. Quantification of intracellular payload release from polymersome nanoparticles

    PubMed Central

    Scarpa, Edoardo; Bailey, Joanne L.; Janeczek, Agnieszka A.; Stumpf, Patrick S.; Johnston, Alexander H.; Oreffo, Richard O. C.; Woo, Yin L.; Cheong, Ying C.; Evans, Nicholas D.; Newman, Tracey A.

    2016-01-01

    Polymersome nanoparticles (PMs) are attractive candidates for spatio-temporal controlled delivery of therapeutic agents. Although many studies have addressed cellular uptake of solid nanoparticles, there is very little data available on intracellular release of molecules encapsulated in membranous carriers, such as polymersomes. Here, we addressed this by developing a quantitative assay based on the hydrophilic dye, fluorescein. Fluorescein was encapsulated stably in PMs of mean diameter 85 nm, with minimal leakage after sustained dialysis. No fluorescence was detectable from fluorescein PMs, indicating quenching. Following incubation of L929 cells with fluorescein PMs, there was a gradual increase in intracellular fluorescence, indicating PM disruption and cytosolic release of fluorescein. By combining absorbance measurements with flow cytometry, we quantified the real-time intracellular release of a fluorescein at a single-cell resolution. We found that 173 ± 38 polymersomes released their payload per cell, with significant heterogeneity in uptake, despite controlled synchronisation of cell cycle. This novel method for quantification of the release of compounds from nanoparticles provides fundamental information on cellular uptake of nanoparticle-encapsulated compounds. It also illustrates the stochastic nature of population distribution in homogeneous cell populations, a factor that must be taken into account in clinical use of this technology. PMID:27404770

  13. Lysozyme loading and release from Se doped hydroxyapatite nanoparticles.

    PubMed

    Wang, Yanhua; Hao, Hang; Zhang, Shengmin

    2016-04-01

    Element-substituted hydroxyapatite (HA) based nanocomposites have become a promising therapeutic material for improving bone defect repair. Selenium substituted HA nanoparticles can both induce apoptosis of bone tumor cells and enhance osteointegration. However, the effect of selenite ions on the proteins in combination with the HA nanoparticles remains to be elucidated. Here, we investigated the influence of selenium doping concentration on the loading and release of lysozyme (LSM) as a model protein drug. The selenium substituted HA-LSM composites with different doping concentrations were synthesized and characterized. The subsequent delivery of lysozyme was studied in a phosphate buffer solution (PBS). We found that selenium substituted HA-LSM composites with Se:P=10% showed the highest amount of lysozyme loading (41.7%), whereas the amount of lysozyme loaded in undoped HA nanoparticles was the lowest (34.1%). The doped selenium interacts with lysozyme molecules, which leads to the increase of β-sheet and unordered, and the decrease of self-association, α-helix and β-turns in protein structures. Moreover, selenium addition significantly slows the protein release from HA-LSM composites. The composites with Se:P=10% release lysozyme at the slightly slower rate among the samples with different Se doping concentrations. It also shows that the released lysozyme retains most of its enzymatic activity.

  14. Lysozyme loading and release from Se doped hydroxyapatite nanoparticles.

    PubMed

    Wang, Yanhua; Hao, Hang; Zhang, Shengmin

    2016-04-01

    Element-substituted hydroxyapatite (HA) based nanocomposites have become a promising therapeutic material for improving bone defect repair. Selenium substituted HA nanoparticles can both induce apoptosis of bone tumor cells and enhance osteointegration. However, the effect of selenite ions on the proteins in combination with the HA nanoparticles remains to be elucidated. Here, we investigated the influence of selenium doping concentration on the loading and release of lysozyme (LSM) as a model protein drug. The selenium substituted HA-LSM composites with different doping concentrations were synthesized and characterized. The subsequent delivery of lysozyme was studied in a phosphate buffer solution (PBS). We found that selenium substituted HA-LSM composites with Se:P=10% showed the highest amount of lysozyme loading (41.7%), whereas the amount of lysozyme loaded in undoped HA nanoparticles was the lowest (34.1%). The doped selenium interacts with lysozyme molecules, which leads to the increase of β-sheet and unordered, and the decrease of self-association, α-helix and β-turns in protein structures. Moreover, selenium addition significantly slows the protein release from HA-LSM composites. The composites with Se:P=10% release lysozyme at the slightly slower rate among the samples with different Se doping concentrations. It also shows that the released lysozyme retains most of its enzymatic activity. PMID:26838882

  15. Measurement of Nanoparticles Release during Drilling of Polymer Nanocomposites

    NASA Astrophysics Data System (ADS)

    Gendre, L.; Marchante Rodriguez, V.; Abhyankar, H.; Blackburn, K.; Brighton, J. L.

    2015-05-01

    Nanomaterials are one of the promising technologies of this century. The Project on Emerging Nanotechnologies [1] reports more than 1600 consumer products based on nanotechnology that are currently on the market and advantages link to the reinforcement of polymeric materials using nano-fillers are not to demonstrate anymore. However, the concerns about safety and its consumer perception can slow down the acceptance of nanocomposites. Indeed, during its life-cycle, a nanotechnology-based product can release nano-sized particles exposing workers, consumers and environment and the risk involved in the use and disposal of such particles is not well known. The current legislation concerning chemicals and environment protection doesn't explicitly cover nanomaterials and changes undergone by nanoparticles during the products’ life cycle. Also, the possible physio-chemical changes that the nanoparticles may undergo during its life cycle are unknown. Industries need a standard method to evaluate nanoparticles release during products’ life cycle in order to improve the knowledge in nanomaterials risk assessment and the legislation, and to inform customers about the safety of nanomaterials and nanoproducts. This work aims to propose a replicable method in order to assess the release of nanoparticles during the machining of nanocomposites in a controlled environment. For this purpose, a new experimental set-up was implemented and issues observed in previous methods (background noise due to uncontrolled ambient environment and the process itself, unrepeatable machining parameters) were solved. A characterisation and validation of the chamber used is presented in this paper. Also, preliminary testing on drilling of polymer-based nanocomposites (Polyamide-6/Glass Fibre reinforced with nano-SiO2) manufactured by extrusion and injection moulding were achieved.

  16. Sequential release of nanoparticle payloads from ultrasonically burstable capsules.

    PubMed

    Kennedy, Stephen; Hu, Jennifer; Kearney, Cathal; Skaat, Hadas; Gu, Luo; Gentili, Marco; Vandenburgh, Herman; Mooney, David

    2016-01-01

    In many biomedical contexts ranging from chemotherapy to tissue engineering, it is beneficial to sequentially present bioactive payloads. Explicit control over the timing and dose of these presentations is highly desirable. Here, we present a capsule-based delivery system capable of rapidly releasing multiple payloads in response to ultrasonic signals. In vitro, these alginate capsules exhibited excellent payload retention for up to 1 week when unstimulated and delivered their entire payloads when ultrasonically stimulated for 10-100 s. Shorter exposures (10 s) were required to trigger delivery from capsules embedded in hydrogels placed in a tissue model and did not result in tissue heating or death of encapsulated cells. Different types of capsules were tuned to rupture in response to different ultrasonic stimuli, thus permitting the sequential, on-demand delivery of nanoparticle payloads. As a proof of concept, gold nanoparticles were decorated with bone morphogenetic protein-2 to demonstrate the potential bioactivity of nanoparticle payloads. These nanoparticles were not cytotoxic and induced an osteogenic response in mouse mesenchymal stem cells. This system may enable researchers and physicians to remotely regulate the timing, dose, and sequence of drug delivery on-demand, with a wide range of clinical applications ranging from tissue engineering to cancer treatment. PMID:26496382

  17. Sequential release of nanoparticle payloads from ultrasonically burstable capsules.

    PubMed

    Kennedy, Stephen; Hu, Jennifer; Kearney, Cathal; Skaat, Hadas; Gu, Luo; Gentili, Marco; Vandenburgh, Herman; Mooney, David

    2016-01-01

    In many biomedical contexts ranging from chemotherapy to tissue engineering, it is beneficial to sequentially present bioactive payloads. Explicit control over the timing and dose of these presentations is highly desirable. Here, we present a capsule-based delivery system capable of rapidly releasing multiple payloads in response to ultrasonic signals. In vitro, these alginate capsules exhibited excellent payload retention for up to 1 week when unstimulated and delivered their entire payloads when ultrasonically stimulated for 10-100 s. Shorter exposures (10 s) were required to trigger delivery from capsules embedded in hydrogels placed in a tissue model and did not result in tissue heating or death of encapsulated cells. Different types of capsules were tuned to rupture in response to different ultrasonic stimuli, thus permitting the sequential, on-demand delivery of nanoparticle payloads. As a proof of concept, gold nanoparticles were decorated with bone morphogenetic protein-2 to demonstrate the potential bioactivity of nanoparticle payloads. These nanoparticles were not cytotoxic and induced an osteogenic response in mouse mesenchymal stem cells. This system may enable researchers and physicians to remotely regulate the timing, dose, and sequence of drug delivery on-demand, with a wide range of clinical applications ranging from tissue engineering to cancer treatment.

  18. Drug encapsulation and release behavior of telechelic nanoparticles

    NASA Astrophysics Data System (ADS)

    Zhang, Shimiao; Arshad, Muhammad; Ullah, Aman

    2015-10-01

    The encapsulation and release of hydrophobic drug, carbamazepine (CBZ) was investigated using three previously synthesized amphiphilic Lipid-b-poly(ethylene glycol) (Lipid-PEG) conjugates. Their micellization, drug encapsulation, and release behavior was investigated by dynamic light scattering (DLS), transmission electron microscope (TEM), and fluorescence spectroscopy. The highest capacity of drug entrapment was observed for the CPE-PEG-a telechelic with the shorter PEG block and the size of the nanoparticles decreased evidently after the drug was loaded, while a slight decrease in size was also observed for the CPE-PEG-b telechelic with longer PEG block and the three-armed CPE-GE conjugate. TEM images showed that all three types of the drug-loaded micelles had spherical or near-spherical morphology. In the study of the in vitro drug release, slower drug-release patterns were observed for CPE-PEG-a and CPE-GE micelles. Almost all the drug entrapped inside the three types of micelles could be released within 50 h.

  19. Nanoparticles with entrapped α-tocopherol: synthesis, characterization, and controlled release

    NASA Astrophysics Data System (ADS)

    Zigoneanu, Imola Gabriela; Astete, Carlos Ernesto; Mirela Sabliov, Cristina

    2008-03-01

    An emulsion evaporation method was used to synthesize spherical poly(DL-lactide-co-glycolide) (PLGA) nanoparticles with entrapped α-tocopherol. Two different surfactants were used: sodium dodecyl sulfate (SDS) and poly(vinyl alcohol) (PVA). For SDS nanoparticles, the size of the nanoparticles decreased significantly with the entrapment of α-tocopherol in the PLGA matrix, while the size of PVA nanoparticles remained unchanged. The polydispersity index after synthesis was under 0.100 for PVA nanoparticles and around 0.150 for SDS nanoparticles. The zeta potential was negative for all PVA nanoparticles. The entrapment efficiency of α-tocopherol in the polymeric matrix was approximately 89% and 95% for nanoparticles with 8% and 16% α-tocopherol theoretical loading, respectively. The residual PVA associated with the nanoparticles after purification was approximately 6% ( w/w relative to the nanoparticles). The release profile showed an initial burst followed by a slower release of the α-tocopherol entrapped inside the PLGA matrix. The release for nanoparticles with 8% α-tocopherol theoretical loading (86% released in the first hour) was faster than the release for the nanoparticles with 16% α-tocopherol theoretical loading (34% released in the first hour).

  20. Enzyme-responsive nanoparticles for drug release and diagnostics.

    PubMed

    de la Rica, Roberto; Aili, Daniel; Stevens, Molly M

    2012-08-01

    Enzymes are key components of the bionanotechnology toolbox that possess exceptional biorecognition capabilities and outstanding catalytic properties. When combined with the unique physical properties of nanomaterials, the resulting enzyme-responsive nanoparticles can be designed to perform functions efficiently and with high specificity for the triggering stimulus. This powerful concept has been successfully applied to the fabrication of drug delivery schemes where the tissue of interest is targeted via release of cargo triggered by the biocatalytic action of an enzyme. Moreover, the chemical transformation of the carrier by the enzyme can also generate therapeutic molecules, therefore paving the way to design multimodal nanomedicines with synergistic effects. Dysregulation of enzymatic activity has been observed in a number of severe pathological conditions, and this observation is useful not only to program drug delivery in vivo but also to fabricate ultrasensitive sensors for diagnosing these diseases. In this review, several enzyme-responsive nanomaterials such as polymer-based nanoparticles, liposomes, gold nanoparticles and quantum dots are introduced, and the modulation of their physicochemical properties by enzymatic activity emphasized. When known, toxicological issues related to the utilization nanomaterials are highlighted. Key examples of enzyme-responsive nanomaterials for drug delivery and diagnostics are presented, classified by the type of effector biomolecule, including hydrolases such as proteases, lipases and glycosidases, and oxidoreductases. PMID:22266127

  1. Release Kinetics of Paclitaxel and Cisplatin from Two and Three Layered Gold Nanoparticles

    PubMed Central

    England, Christopher G.; Miller, M. Clarke; Kuttan, Ashani; Trent, John O.; Frieboes, Hermann B.

    2015-01-01

    Gold nanoparticles functionalized with biologically-compatible layers may achieve stable drug release while avoiding adverse effects in cancer treatment. We study cisplatin and paclitaxel release from gold cores functionalized with hexadecanethiol (TL) and phosphatidylcholine (PC) to form two-layer nanoparticles, or TL, PC, and high density lipoprotein (HDL) to form three-layer nanoparticles. Drug release was monitored for 14 days to assess long term effects of the core surface modifications on release kinetics. Release profiles were fitted to previously developed kinetic models to differentiate possible release mechanisms. The hydrophilic drug (cisplatin) showed an initial (5-hr.) burst, followed by a steady release over 14 days. The hydrophobic drug (paclitaxel) showed a steady release over the same time period. Two layer nanoparticles released 64.0 ± 2.5% of cisplatin and 22.3 ± 1.5% of paclitaxel, while three layer nanoparticles released the entire encapsulated drug. The Korsmeyer-Peppas model best described each release scenario, while the simplified Higuchi model also adequately described paclitaxel release from the two layer formulation. We conclude that functionalization of gold nanoparticles with a combination of TL and PC may help to modulate both hydrophilic and hydrophobic drug release kinetics, while the addition of HDL may enhance long term release of hydrophobic drug. PMID:25753197

  2. Externally Controlled Triggered-Release of Drug from PLGA Micro and Nanoparticles

    PubMed Central

    Hua, Xin; Tan, Shengnan; Bandara, H. M. H. N.; Fu, Yujie; Liu, Siguo; Smyth, Hugh D. C.

    2014-01-01

    Biofilm infections are extremely hard to eradicate and controlled, triggered and controlled drug release properties may prolong drug release time. In this study, the ability to externally control drug release from micro and nanoparticles was investigated. We prepared micro/nanoparticles containing ciprofloxacin (CIP) and magnetic nanoparticles encapsulated in poly (lactic-co-glycolic acid) PLGA. Both micro/nanoparticles were observed to have narrow size distributions. We investigated and compared their passive and externally triggered drug release properties based on their different encapsulation structures for the nano and micro systems. In passive release studies, CIP demonstrated a fast rate of release in first 2 days which then slowed and sustained release for approximately 4 weeks. Significantly, magnetic nanoparticles containing systems all showed ability to have triggered drug release when exposed to an external oscillating magnetic field (OMF). An experiment where the OMF was turned on and off also confirmed the ability to control the drug release in a pulsatile manner. The magnetically triggered release resulted in a 2-fold drug release increase compared with normal passive release. To confirm drug integrity following release, the antibacterial activity of released drug was evaluated in Pseudomonas aeruginosa biofilms in vitro. CIP maintained its antimicrobial activity after encapsulation and triggered release. PMID:25479357

  3. Externally controlled triggered-release of drug from PLGA micro and nanoparticles.

    PubMed

    Hua, Xin; Tan, Shengnan; Bandara, H M H N; Fu, Yujie; Liu, Siguo; Smyth, Hugh D C

    2014-01-01

    Biofilm infections are extremely hard to eradicate and controlled, triggered and controlled drug release properties may prolong drug release time. In this study, the ability to externally control drug release from micro and nanoparticles was investigated. We prepared micro/nanoparticles containing ciprofloxacin (CIP) and magnetic nanoparticles encapsulated in poly (lactic-co-glycolic acid) PLGA. Both micro/nanoparticles were observed to have narrow size distributions. We investigated and compared their passive and externally triggered drug release properties based on their different encapsulation structures for the nano and micro systems. In passive release studies, CIP demonstrated a fast rate of release in first 2 days which then slowed and sustained release for approximately 4 weeks. Significantly, magnetic nanoparticles containing systems all showed ability to have triggered drug release when exposed to an external oscillating magnetic field (OMF). An experiment where the OMF was turned on and off also confirmed the ability to control the drug release in a pulsatile manner. The magnetically triggered release resulted in a 2-fold drug release increase compared with normal passive release. To confirm drug integrity following release, the antibacterial activity of released drug was evaluated in Pseudomonas aeruginosa biofilms in vitro. CIP maintained its antimicrobial activity after encapsulation and triggered release.

  4. Release of Magnetic Nanoparticles from Cell-Encapsulating Biodegradable Nanobiomaterials

    PubMed Central

    Xu, Feng; Inci, Fatih; Mullick, Omer; Gurkan, Umut Atakan; Sung, Yuree; Kavaz, Doga; Li, Baoqiang; Denkbas, Emir Baki; Demirci, Utkan

    2013-01-01

    The future of tissue engineering requires development of intelligent biomaterials using nanoparticles. Magnetic nanoparticles (MNPs) have several applications in biology and medicine; one example is Food and Drug Administration (FDA)-approved contrast agents in magnetic resonance imaging. Recently, MNPs have been encapsulated within cell-encapsulating hydrogels to create novel nanobiomaterials (i.e., M-gels), which can be manipulated and assembled in magnetic fields. The M-gels can be used as building blocks for bottom-up tissue engineering to create 3D tissue constructs. For tissue engineering applications of M-gels, it is essential to study the release of encapsulated MNPs from the hydrogel polymer network and the effect of MNPs on hydrogel properties, including mechanical characteristics, porosity, swelling behavior, and cellular response (e.g., viability, growth). Therefore, we evaluated the release of MNPs from photocrosslinkable gelatin methacrylate hydrogels as the polymer network undergoes biodegradation using inductively coupled plasma atomic emission spectroscopy. MNP release correlated linearly with hydrogel biodegradation rate with correlation factors (Pearson product moment correlation coefficient) of 0.96 ± 0.03 and 0.99 ± 0.01 for MNP concentrations of 1% and 5%, respectively. We also evaluated the effect of MNPs on hydrogel mechanical properties, porosity, and swelling behavior, as well as cell viability and growth in MNP-encapsulating hydrogels. Fibroblasts encapsulated with MNPs in hydrogels remained viable (>80% at t = 144 h) and formed microtissue constructs in culture (t = 144 h). These results indicated that MNP-encapsulating hydrogels show promise as intelligent nanobiomaterials, with great potential to impact broad areas of bioengineering, including tissue engineering, regenerative medicine, and pharmaceutical applications. PMID:22680777

  5. Release of magnetic nanoparticles from cell-encapsulating biodegradable nanobiomaterials.

    PubMed

    Xu, Feng; Inci, Fatih; Mullick, Omer; Gurkan, Umut Atakan; Sung, Yuree; Kavaz, Doga; Li, Baoqiang; Denkbas, Emir Baki; Demirci, Utkan

    2012-08-28

    The future of tissue engineering requires development of intelligent biomaterials using nanoparticles. Magnetic nanoparticles (MNPs) have several applications in biology and medicine; one example is Food and Drug Administration (FDA)-approved contrast agents in magnetic resonance imaging. Recently, MNPs have been encapsulated within cell-encapsulating hydrogels to create novel nanobiomaterials (i.e., M-gels), which can be manipulated and assembled in magnetic fields. The M-gels can be used as building blocks for bottom-up tissue engineering to create 3D tissue constructs. For tissue engineering applications of M-gels, it is essential to study the release of encapsulated MNPs from the hydrogel polymer network and the effect of MNPs on hydrogel properties, including mechanical characteristics, porosity, swelling behavior, and cellular response (e.g., viability, growth). Therefore, we evaluated the release of MNPs from photocrosslinkable gelatin methacrylate hydrogels as the polymer network undergoes biodegradation using inductively coupled plasma atomic emission spectroscopy. MNP release correlated linearly with hydrogel biodegradation rate with correlation factors (Pearson product moment correlation coefficient) of 0.96 ± 0.03 and 0.99 ± 0.01 for MNP concentrations of 1% and 5%, respectively. We also evaluated the effect of MNPs on hydrogel mechanical properties, porosity, and swelling behavior, as well as cell viability and growth in MNP-encapsulating hydrogels. Fibroblasts encapsulated with MNPs in hydrogels remained viable (>80% at t = 144 h) and formed microtissue constructs in culture (t = 144 h). These results indicated that MNP-encapsulating hydrogels show promise as intelligent nanobiomaterials, with great potential to impact broad areas of bioengineering, including tissue engineering, regenerative medicine, and pharmaceutical applications.

  6. Drug loading and release on tumor cells using silk fibroin-albumin nanoparticles as carriers

    NASA Astrophysics Data System (ADS)

    Subia, B.; Kundu, S. C.

    2013-01-01

    Polymeric and biodegradable nanoparticles are frequently used in drug delivery systems. In this study silk fibroin-albumin blended nanoparticles were prepared using the desolvation method without any surfactant. These nanoparticles are easily internalized by the cells, reside within perinuclear spaces and act as carriers for delivery of the model drug methotrexate. Methotrexate loaded nanoparticles have better encapsulation efficiency, drug loading ability and less toxicity. The in vitro release behavior of methotrexate from the nanoparticles suggests that about 85% of the drug gets released after 12 days. The encapsulation and loading of a drug would depend on factors such as size, charge and hydrophobicity, which affect drug release. MTT assay and conjugation of particles with FITC demonstrate that the silk fibroin-albumin nanoparticles do not affect the viability and biocompatibility of cells. This blended nanoparticle, therefore, could be a promising nanocarrier for the delivery of drugs and other bioactive molecules.

  7. Bovine serum albumin nanoparticles as controlled release carrier for local drug delivery to the inner ear

    NASA Astrophysics Data System (ADS)

    Yu, Zhan; Yu, Min; Zhang, Zhibao; Hong, Ge; Xiong, Qingqing

    2014-07-01

    Nanoparticles have attracted increasing attention for local drug delivery to the inner ear recently. Bovine serum albumin (BSA) nanoparticles were prepared by desolvation method followed by glutaraldehyde fixation or heat denaturation. The nanoparticles were spherical in shape with an average diameter of 492 nm. The heat-denatured nanoparticles had good cytocompatibility. The nanoparticles could adhere on and penetrate through the round window membrane of guinea pigs. The nanoparticles were analyzed as drug carriers to investigate the loading capacity and release behaviors. Rhodamine B was used as a model drug in this paper. Rhodamine B-loaded nanoparticles showed a controlled release profile and could be deposited on the osseous spiral lamina. We considered that the bovine serum albumin nanoparticles may have potential applications in the field of local drug delivery in the treatment of inner ear disorders.

  8. Formulation effects on the release of silica dioxide nanoparticles from paint debris to water.

    PubMed

    Zuin, Stefano; Massari, Andrea; Ferrari, Arlen; Golanski, Luana

    2014-04-01

    Waterborne paints with integrated nanoparticles have been recently introduced into the market as nanoparticles offer improved or novel functionalities to paints. However, the release of nanoparticles during the life cycle of nano-enhanced paint has only been studied to a very limited extent. The paint composition could determine in what quantities and forms the nanoparticles are released. In this work, paint formulations containing the same amount of silicon dioxide (SiO2) nanoparticles but differing in the pigment volume concentration (PVC) and in amount and type of binder and pigment, were studied through leaching test to investigate the influence of these parameters on release of Si from paint. The results indicate greater release of Si, about 1.7 wt.% of the SiO2 nanoparticles in the paint, for paint formulated with higher PVC value (63%), suggesting that the PVC is a crucial factor for release of SiO2 nanoparticles from paints. This hypothesis was also based on the fact that agglomerates of SiO2 nanoparticles were only found in leachates from paint with higher PVC. A paint sample with the higher amount of binder and less calcite filler exhibited a lower release of Si among the paints with a low PVC value (35%), and no SiO2 particles were detected in leachates collected from this paint. This could be due to the fact that a high portion of binder forms a suitable matrix to hold the SiO2 ENPs in paint. The paint sample in which the amount of calcite was partially substituted with TiO2 pigment did not show an important reduction on Si release. Our work suggests that paint debris containing SiO2 nanoparticles may release a limited amount of Si into the environment, and that by adjusting the properties of the binder in combination with common pigments it is possible to reduce the release of SiO2 nanoparticles. PMID:24468504

  9. Formulation effects on the release of silica dioxide nanoparticles from paint debris to water.

    PubMed

    Zuin, Stefano; Massari, Andrea; Ferrari, Arlen; Golanski, Luana

    2014-04-01

    Waterborne paints with integrated nanoparticles have been recently introduced into the market as nanoparticles offer improved or novel functionalities to paints. However, the release of nanoparticles during the life cycle of nano-enhanced paint has only been studied to a very limited extent. The paint composition could determine in what quantities and forms the nanoparticles are released. In this work, paint formulations containing the same amount of silicon dioxide (SiO2) nanoparticles but differing in the pigment volume concentration (PVC) and in amount and type of binder and pigment, were studied through leaching test to investigate the influence of these parameters on release of Si from paint. The results indicate greater release of Si, about 1.7 wt.% of the SiO2 nanoparticles in the paint, for paint formulated with higher PVC value (63%), suggesting that the PVC is a crucial factor for release of SiO2 nanoparticles from paints. This hypothesis was also based on the fact that agglomerates of SiO2 nanoparticles were only found in leachates from paint with higher PVC. A paint sample with the higher amount of binder and less calcite filler exhibited a lower release of Si among the paints with a low PVC value (35%), and no SiO2 particles were detected in leachates collected from this paint. This could be due to the fact that a high portion of binder forms a suitable matrix to hold the SiO2 ENPs in paint. The paint sample in which the amount of calcite was partially substituted with TiO2 pigment did not show an important reduction on Si release. Our work suggests that paint debris containing SiO2 nanoparticles may release a limited amount of Si into the environment, and that by adjusting the properties of the binder in combination with common pigments it is possible to reduce the release of SiO2 nanoparticles.

  10. Controlled release of tamoxifen citrate encapsulated in cross-linked guar gum nanoparticles.

    PubMed

    Sarmah, Jayanta K; Mahanta, Rita; Bhattacharjee, Saibal Kanti; Mahanta, Ranadeep; Biswas, Angshuman

    2011-10-01

    Natural polysaccharides, due to their outstanding merits, have received more and more attention in the field of drug delivery. In the present study tamoxifen citrate, TMX (a non-steroidal antiestrogenic drug) loaded guar gum nanoparticles, GG NPs, crosslinked with glutaraldehyde were prepared for treatment of breast cancer. An oil in water (o/w) emulsion polymer cross-linking method was employed for preparation of blank and drug loaded sustained release nature biodegradable nanoparticles. Prepared nanoparticles were characterized by morphology in scanning electron microscope (SEM), size distribution in transmission electron microscope (TEM), TMX loading by high performance liquid chromatography (HPLC) and in vitro drug release characteristics. An overall sustained release of the drug from the biodegradable nanoparticles was observed in in vitro release studies. The release of TMX from GG NPs was found to be effected by guar gum and glutaraldehyde concentration. Regression coefficient (R(2)) analysis suggested that the predominant mechanism behind the drug release from the nanoparticles was time dependent release and diffusion. In vivo studies on female albino mice demonstrated maximum uptake of the drug by mammary tissue after 24h of administration with drug loaded guar gum nanoparticles in comparison with that with the tablet form of the drug. These findings demonstrate that controlled release of TMX from GG NPs could be a potential alternative pharmaceutical formulation in passive targeting of TMX in breast cancer treatments. PMID:21641924

  11. Poly(lactic acid)/chitosan hybrid nanoparticles for controlled release of anticancer drug.

    PubMed

    Wang, Wenlong; Chen, Shu; Zhang, Liang; Wu, Xi; Wang, Jiexin; Chen, Jian-Feng; Le, Yuan

    2015-01-01

    Poly(lactic acid) (PLA) is a kind of non-toxic biological materials with excellent absorbability, biocompatibility and biodegradability, which can be used for drug release, tissue engineering and surgical treatment applications. In this study, we prepared chitosan modified PLA nanoparticles as carriers for encapsulation of docetaxel by anti-solvent precipitation method. The morphology, particle size, zeta potential and composition of the PLA/chitosan were characterized by SEM, DLS, FTIR and XPS. As-prepared PLA/chitosan particles exhibited average size of 250 nm and showed very narrow distribution with polydispersity index of 0.098. Their large surface charge-ability was confirmed by zeta potential value of 53.9 mV. Docetaxel was released from PLA/chitosan nanoparticles with 40% initial burst release in 5 h and 70% cumulative release within 24 h, while from PLA nanoparticles 65% of docetaxel was released in 5h. In vitro drug release study demonstrated that PLA/chitosan nanoparticles prolonged drug release and decreased the burst release over the unmodified PLA nanoparticles. These results illustrated high potential of chitosan modified PLA nanoparticles for usage as anticancer drug carriers. PMID:25492016

  12. Poly(lactic acid)/chitosan hybrid nanoparticles for controlled release of anticancer drug.

    PubMed

    Wang, Wenlong; Chen, Shu; Zhang, Liang; Wu, Xi; Wang, Jiexin; Chen, Jian-Feng; Le, Yuan

    2015-01-01

    Poly(lactic acid) (PLA) is a kind of non-toxic biological materials with excellent absorbability, biocompatibility and biodegradability, which can be used for drug release, tissue engineering and surgical treatment applications. In this study, we prepared chitosan modified PLA nanoparticles as carriers for encapsulation of docetaxel by anti-solvent precipitation method. The morphology, particle size, zeta potential and composition of the PLA/chitosan were characterized by SEM, DLS, FTIR and XPS. As-prepared PLA/chitosan particles exhibited average size of 250 nm and showed very narrow distribution with polydispersity index of 0.098. Their large surface charge-ability was confirmed by zeta potential value of 53.9 mV. Docetaxel was released from PLA/chitosan nanoparticles with 40% initial burst release in 5 h and 70% cumulative release within 24 h, while from PLA nanoparticles 65% of docetaxel was released in 5h. In vitro drug release study demonstrated that PLA/chitosan nanoparticles prolonged drug release and decreased the burst release over the unmodified PLA nanoparticles. These results illustrated high potential of chitosan modified PLA nanoparticles for usage as anticancer drug carriers.

  13. Development of CNC prototype for the characterization of the nanoparticle release during physical manipulation of nanocomposites.

    PubMed

    Gendre, Laura; Marchante, Veronica; Abhyankar, Hrushikesh A; Blackburn, Kim; Temple, Clive; Brighton, James L

    2016-01-01

    This work focuses on the release of nanoparticles from commercially used nanocomposites during machining operations. A reliable and repeatable method was developed to assess the intentionally exposure to nanoparticles, in particular during drilling. This article presents the description and validation of results obtained from a new prototype used for the measurement and monitoring of nanoparticles in a controlled environment. This methodology was compared with the methodologies applied in other studies. Also, some preliminary experiments on drilling nanocomposites are included. Size, shape and chemical composition of the released nanoparticles were investigated in order to understand their hazard potential. No significant differences were found in the amount of nanoparticles released between samples with and without nanoadditives. Also, no chemical alteration was observed between the dust generated and the bulk material. Finally, further developments of the prototype are proposed.

  14. Development of CNC prototype for the characterization of the nanoparticle release during physical manipulation of nanocomposites.

    PubMed

    Gendre, Laura; Marchante, Veronica; Abhyankar, Hrushikesh A; Blackburn, Kim; Temple, Clive; Brighton, James L

    2016-01-01

    This work focuses on the release of nanoparticles from commercially used nanocomposites during machining operations. A reliable and repeatable method was developed to assess the intentionally exposure to nanoparticles, in particular during drilling. This article presents the description and validation of results obtained from a new prototype used for the measurement and monitoring of nanoparticles in a controlled environment. This methodology was compared with the methodologies applied in other studies. Also, some preliminary experiments on drilling nanocomposites are included. Size, shape and chemical composition of the released nanoparticles were investigated in order to understand their hazard potential. No significant differences were found in the amount of nanoparticles released between samples with and without nanoadditives. Also, no chemical alteration was observed between the dust generated and the bulk material. Finally, further developments of the prototype are proposed. PMID:26889574

  15. Direct Release of Sombrero-Shaped Magnetite Nanoparticles via Nanoimprint Lithography

    SciTech Connect

    Kwon, Byung Seok; Zhang, Wei; Li, Zheng; Krishnan, Kannan M.

    2015-01-10

    Magnetic nanoparticles produced via nanoimprint lithography can change the current paradigm of fabrication processes from chemical “bottom-up” synthesis to “top-down” fabrication. The combination of controlled nondirectional magnetron sputtering, ETFE mold, bilayer lift-off, and dry etching release can control the shape, size, and structure of the fabricated nanoparticles. The resulting magnetic nanoparticles have a novel “sombrero” shape with complex and unique physical/magnetic properties.

  16. Anti-biofilm efficacy of nitric oxide-releasing silica nanoparticles.

    PubMed

    Hetrick, Evan M; Shin, Jae Ho; Paul, Heather S; Schoenfisch, Mark H

    2009-05-01

    The ability of nitric oxide (NO)-releasing silica nanoparticles to kill biofilm-based microbial cells is reported. Biofilms of Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, and Candida albicans were formed in vitro and exposed to NO-releasing silica nanoparticles. Replicative viability experiments revealed that >or= 99% of cells from each type of biofilm were killed via NO release, with the greatest efficacy (>or= 99.999% killing) against gram-negative P. aeruginosa and E. coli biofilms. Cytotoxicity testing demonstrated that the highest dose of NO-releasing silica nanoparticles inhibited fibroblast proliferation to a lesser extent than clinical concentrations of currently administered antiseptics (e.g., chlorhexidine) with proven wound-healing benefits. This study demonstrates the promise of employing nanoparticles for delivering an antimicrobial agent to microbial biofilms.

  17. Solvent mediated microstructures and release behavior of insulin from pH-sensitive nanoparticles.

    PubMed

    Wu, Zhi Min; Guo, Xin Dong; Zhang, Li Juan; Jiang, Wei; Ling, Li; Qian, Yu; Chen, Yun

    2012-06-01

    The insulin loaded nanoparticles composed of poly (lactic-co-glycolic acid) (PLGA) and hydroxypropyl methylcellulose phthalate (HP55) were prepared via the emulsions solvent diffusion method with two different solvents, namely, DMSO and acetone/water. The microstructures of the nanoparticles were studied by the solubility parameters theory, DSC, FTIR, and the nitrogen adsorption technique. Phase-separated PLGA domains were observed from the nanoparticles prepared with both types of solvents. Mesopores were observed from the nanoparticles prepared with DMSO as the solvent and almost did not exist with acetone/water. An in vitro drug release study showed that the pH-sensitivity of nanoparticles was not only attributed to the pH-dependent dissolubility of HP55 but also to the internal microstructure. The formation of mesopores accelerated the release of insulin, leading to no obvious pH-sensitivity of the nanoparticles prepared with DMSO. However, for the nanoparticles prepared with acetone/water, the release of insulin was pH-dependent. The results demonstrated that solvents played an important role in affecting the microstructures of nanoparticles, which influenced markedly the insulin release behavior.

  18. Release of quantum dot nanoparticles in porous media: Role of cation exchange and aging time

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Understanding the fate and transport of engineered nanoparticles (ENPs) in subsurface environments is required for developing the best strategy for waste management and disposal of these materials. In this study, the deposition and release of quantum dot (QD) nanoparticles were studied in saturated ...

  19. In vitro controlled release of Rifampicin through liquid-crystalline folate nanoparticles.

    PubMed

    Parmar, Rohan; Misra, Rahul; Mohanty, Sanat

    2015-05-01

    Rifampicin is one of the frontline drugs for tuberculosis therapy but poor bioavailability of Rifampicin in combination with other anti-tuberculosis drugs is a subject of concern. Nano-based formulations for sustained release of anti-tubercular drugs have been shown to increase antibacterial efficacy and pharmacokinetic behavior. In the present study, liquid-crystalline folate nanoparticles were designed for sustained delivery of Rifampicin and its in vitro release study is reported. Liquid-crystalline nanoparticles of biocompatible folate ions consist of self assembled structures, resulting in high encapsulation, controlled release and low drug losses of about 20-30%, which is significant in itself. This study reports the size-control method of forming Rifampicin encapsulated folate nanoparticles as well as the parameters to control the release profiles of Rifampicin through these nanoparticles. These designs are able to present sustained release for over 25 days. The effect of different parameters such as nanoparticles size, type of cross-linking cation, cross-linking cation concentration and drug-loading on Rifampicin release was studied in vitro. The intracellular uptake and low cytotoxicity of nanoparticles by alveolar macrophages was also demonstrated using fluorescence microscopy and MTT assay respectively.

  20. Towards the development of multifunctional chitosan-based iron oxide nanoparticles: Optimization and modelling of doxorubicin release.

    PubMed

    Soares, Paula I P; Sousa, Ana Isabel; Ferreira, Isabel M M; Novo, Carlos M M; Borges, João Paulo

    2016-11-20

    In the present work composite nanoparticles with a magnetic core and a chitosan-based shell were produced as drug delivery systems for doxorubicin (DOX). The results show that composite nanoparticles with a hydrodynamic diameter within the nanometric range are able to encapsulate more DOX than polymeric nanoparticles alone corresponding also to a higher drug release. Moreover the synthesis method of the iron oxide nanoparticles influences the total amount of DOX released and a high content of iron oxide nanoparticles inhibits DOX release. The modelling of the experimental results revealed a release mechanism dominated by Fickian diffusion. PMID:27561489

  1. Towards the development of multifunctional chitosan-based iron oxide nanoparticles: Optimization and modelling of doxorubicin release.

    PubMed

    Soares, Paula I P; Sousa, Ana Isabel; Ferreira, Isabel M M; Novo, Carlos M M; Borges, João Paulo

    2016-11-20

    In the present work composite nanoparticles with a magnetic core and a chitosan-based shell were produced as drug delivery systems for doxorubicin (DOX). The results show that composite nanoparticles with a hydrodynamic diameter within the nanometric range are able to encapsulate more DOX than polymeric nanoparticles alone corresponding also to a higher drug release. Moreover the synthesis method of the iron oxide nanoparticles influences the total amount of DOX released and a high content of iron oxide nanoparticles inhibits DOX release. The modelling of the experimental results revealed a release mechanism dominated by Fickian diffusion.

  2. Self-assembled liquid-crystalline folate nanoparticles for in vitro controlled release of doxorubicin.

    PubMed

    Misra, Rahul; Mohanty, Sanat

    2015-02-01

    Liquid-crystalline folate nanoparticles are ordered in structure which offers several advantages like high encapsulation of drugs, controlled release rates, biocompatible in nature. Moreover, it facilitates the cellular uptake of nanodrugs without any extra step of folate ligand based targeting. The size of these nanocarriers as well as the release profiles of drugs from these nano-carriers can be controlled precisely. Folate molecules self-assemble in ordered stacks and columns even at low concentration of 0.1wt%. Doxorubicin molecules get intercalated within the folate stacks and are developed into nanoparticles. These nanoparticles are composed of highly ordered folate self-assembly which encapsulate doxorubicin molecules. These drug molecules can be released in a controlled manner by disrupting this assembly in the environment of monovalent cations. The ordered structure of folate nanoparticles offers low drug losses of about 4-5%, which is significant in itself. This study reports the size-control method of forming doxorubicin encapsulated folate nanoparticles as well as the parameters to control the release rates of doxorubicin through liquid-crystalline folate nanoparticles. It has been demonstrated that doxorubicin release rates can be controlled by controlling the size of the nanoparticles, cross-linking cation and cross-linking concentration. The effect of different factors like drug loading, release medium, and pH of the medium on doxorubicin release rates was also studied. Moreover, this study also addresses the comparative in vitro cytotoxic performance of Doxorubicin loaded folate nanoparticles and cellular uptake of nano-carriers on cancer and normal cell line.

  3. pH-Triggered release from surface-modified poly(lactic-co-glycolic acid) nanoparticles

    PubMed Central

    Häuser, Manuel; Langer, Klaus

    2015-01-01

    Summary Nanoparticles (NP) of poly(lactic-co-glycolic acid) (PLGA) represent a promising biodegradable drug delivery system. We suggest here a two-step release system of PLGA nanoparticles with a pH-tunable polymeric shell, providing an initial pH-triggered step, releasing a membrane-toxic cationic compound. PLGA nanoparticles are coated by polyelectrolytes using the layer-by-layer self-assembly technique, employing poly(acrylic acid) (PAA) as a pH-sensitive component and poly(diallyldimethylammonium chloride) (PDADMAC) as the releasable polycation. The pH during multilayer deposition plays a major role and influences the titration curve of the layer system. The pH-tunability of PAA is intensively investigated with regard to the pH region, in which the particle system becomes uncharged. The isoelectric point can be shifted by employing suitable deposition pH values. The release is investigated by quantitative 1H NMR, yielding a pH-dependent release curve. A release of PDADMAC is initiated by a decrease of the pH value. The released amount of polymer, as quantified by 1H NMR analysis, clearly depends on the pH value and thus on the state of deprotonation of the pH-sensitive PAA layer. Subsequent incubation of the nanoparticles with high concentrations of sodium chloride shows no further release and thus demonstrates the pH-driven release to be quantitative. PMID:26885463

  4. PLGA Biodegradable Nanoparticles Containing Perphenazine or Chlorpromazine Hydrochloride: Effect of Formulation and Release

    PubMed Central

    Halayqa, Mohammed; Domańska, Urszula

    2014-01-01

    In our study, poly(dl-lactide-co-glycolide) (PLGA) nanoparticles loaded with perphenazine (PPH) and chlorpromazine hydrochloride (CPZ-HCl) were formulated by emulsion solvent evaporation technique. The effect of various processing variables, including PLGA concentration, theoretical drug loading, poly(vinyl alcohol) (PVA) concentration and the power of sonication were assessed systematically to obtain higher encapsulation efficiency and to minimize the nanoparticles size. By the optimization formulation process, the nanoparticles were obtained in submicron size from 325.5 ± 32.4 to 374.3 ± 10.1 nm for nanoparticles loaded with PPH and CPZ-HCl, respectively. Nanoparticles observed by scanning electron microscopy (SEM) presented smooth surface and spherical shape. The encapsulation efficiency of nanoparticles loaded with PPH and CPZ-HCl were 83.9% and 71.0%, respectively. The drug loading were 51.1% and 39.4% for PPH and CPZ-HCl, respectively. Lyophilized nanoparticles with different PLGA concentration 0.8%, 1.3% and 1.6% (w/v) in formulation process were evaluated for in vitro release in phosphate buffered saline (pH = 7.4) by using dialysis bags. The release profile for both drugs have shown that the rate of PPH and CPZ-HCl release were dependent on a size and amount of drugs in the nanoparticles. PMID:25535080

  5. Preparation and nanoencapsulation of l-asparaginase II in chitosan-tripolyphosphate nanoparticles and in vitro release study

    NASA Astrophysics Data System (ADS)

    Bahreini, Elham; Aghaiypour, Khosrow; Abbasalipourkabir, Roghayeh; Mokarram, Ali Rezaei; Goodarzi, Mohammad Taghi; Saidijam, Massoud

    2014-07-01

    This paper describes the production, purification, and immobilization of l-asparaginase II (ASNase II) in chitosan nanoparticles (CSNPs). ASNase II is an effective antineoplastic agent, used in the acute lymphoblastic leukemia chemotherapy. Cloned ASNase II gene ( ansB) in pAED4 plasmid was transformed into Escherichia coli BL21pLysS (DE3) competent cells and expressed under optimal conditions. The lyophilized enzyme was loaded into CSNPs by ionotropic gelation method. In order to get optimal entrapment efficiency, CSNP preparation, chitosan/tripolyphosphate (CS/TPP) ratio, and protein loading were investigated. ASNase II loading into CSNPs was confirmed by Fourier transform infrared (FTIR) spectroscopy, and morphological observation was carried out by transmission electron microscopy. Three absolute CS/TPP ratios were studied. Entrapment efficiency and loading capacity increased with increasing CS and TPP concentration. The best ratio was applied for obtaining optimal ASNase II-loaded CSNPs with the highest entrapment efficiency. Size, zeta potential, entrapment efficiency, and loading capacity of the optimal ASNase II-CSNPs were 340 ± 12 nm, 21.2 ± 3 mV, 76.2% and 47.6%, respectively. The immobilized enzyme showed an increased in vitro half-life in comparison with the free enzyme. The pH and thermostability of the immobilized enzyme was comparable with the free enzyme. This study leads to a better understanding of how to prepare CSNPs, how to achieve high encapsulation efficiency for a high molecular weight protein, and how to prolong the release of protein from CSNPs. A conceptual understanding of biological responses to ASNase II-loaded CSNPs is needed for the development of novel methods of drug delivery.

  6. Size-Tunable and Functional Core-Shell Structured Silica Nanoparticles for Drug Release

    SciTech Connect

    Chi, Fangli; Guo, Ya Nan; Liu, Jun; Liu, Yunling; Huo, Qisheng

    2010-02-18

    Size-tunable silica cross-linked micellar core-shell nanoparticles (SCMCSNs) were successfully synthesized from a Pluronic nonionic surfactant (F127) template system with organic swelling agents such as 1,3,5-trimethylbenzene (TMB) and octanoic acid at room temperature. The size and morphology of SCMCSNs were directly evidenced by TEM imaging and DLS measurements (up to ~90 nm). Pyrene and coumarin 153 (C153) were used as fluorescent probe molecules to investigate the effect and location of swelling agent molecules. Papaverine as a model drug was used to measure the loading capacity and release property of nanoparticles. The swelling agents can enlarge the nanoparticle size and improve the drug loading capacity of nanoparticles. Moreover, the carboxylic acid group of fatty acid can adjust the release behavior of the nanoparticles.

  7. Fabrication of autofluorescent porous silica nanoparticles for redox-responsive drug release.

    PubMed

    Cao, Na; Zhao, Yanbao; Sang, Bin; Wang, Zhihua; Cao, Liuqin; Sun, Lei; Zou, Xueyan

    2016-12-01

    Porous silica nanoparticles were prepared by emulsion-condensation route. The silica nanoparticles with diameter of 50nm have both accessible center-radial large pore channels (19.9nm) and small pore size of 3.5nm. The hierarchical porous structure endows them large pore volume for loading drugs and sustained release property. The silica nanoparticles were further modified with glucose-oxidized glutathione. The formulated Schiff base and disulfide bonds render the silica nanoparticles auto-fluorescent and redox-responsive properties. The cleavage of disulfide bonds caused by reactive thiols facilitates aminomethylbenzoic acid (AMA) release. The release of drug leads to the loss of fluorescence, which would be used to monitor the drug delivery and carrier distribution. PMID:27612720

  8. Magnetic field activated lipid-polymer hybrid nanoparticles for stimuli-responsive drug release.

    PubMed

    Kong, Seong Deok; Sartor, Marta; Hu, Che-Ming Jack; Zhang, Weizhou; Zhang, Liangfang; Jin, Sungho

    2013-03-01

    Stimuli-responsive nanoparticles (SRNPs) offer the potential of enhancing the therapeutic efficacy and minimizing the side-effects of chemotherapeutics by controllably releasing the encapsulated drug at the target site. Currently controlled drug release through external activation remains a major challenge during the delivery of therapeutic agents. Here we report a lipid-polymer hybrid nanoparticle system containing magnetic beads for stimuli-responsive drug release using a remote radio frequency (RF) magnetic field. These hybrid nanoparticles show long-term stability in terms of particle size and polydispersity index in phosphate-buffered saline (PBS). Controllable loading of camptothecin (CPT) and Fe(3)O(4) in the hybrid nanoparticles was demonstrated. RF-controlled drug release from these nanoparticles was observed. In addition, cellular uptake of the SRNPs into MT2 mouse breast cancer cells was examined. Using CPT as a model anticancer drug the nanoparticles showed a significant reduction in MT2 mouse breast cancer cell growth in vitro in the presence of a remote RF field. The ease of preparation, stability, and controllable drug release are the strengths of the platform and provide the opportunity to improve cancer chemotherapy.

  9. Development of subcutaneous sustained release nanoparticles encapsulating low molecular weight heparin.

    PubMed

    Jogala, Satheesh; Rachamalla, Shyam Sunder; Aukunuru, Jithan

    2015-01-01

    The objective of the present research work was to prepare and evaluate sustained release subcutaneous (s.c.) nanoparticles of low molecular weight heparin (LMWH). The nanoparticles were prepared by water-in-oil in-water (w/o/w) emulsion and evaporation method using different grades of polylactide co-glycolide (50:50, 85:15), and different concentrations of polyvinyl alcohol (0.1%, 0.5%, 1%) aqueous solution as surfactant. The fabricated nanoparticles were evaluated for size, shape, zeta potential, encapsulation efficiency, in vitro drug release, and in vivo biological activity (anti-factor Xa activity) using the standard kit. The drug and excipient compatibility was analyzed by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray diffraction (XRD) studies. The formation of nanoparticles was confirmed by scanning electron microscopy; nanoparticles were spherical in shape. The size of prepared nanoparticles was found between 195 nm and 251 nm. The encapsulation efficiency of the nanoparticles was found between 46% and 70%. In vitro drug, release was about 16-38% for 10 days. In vivo drug, release shows the sustained release of drug for 10 days in rats. FTIR studies indicated that there was no loss in chemical integrity of the drug upon fabrication into nanoparticles. DSC and XRD results demonstrated that the drug was changed from the crystalline form to the amorphous form in the formulation during the fabrication process. The results of this study revealed that the s.c. nanoparticles were suitable candidates for sustained delivery of LMWH. PMID:25878975

  10. A slow-release system of bacterial cellulose gel and nanoparticles for hydrophobic active ingredients.

    PubMed

    Numata, Yukari; Mazzarino, Leticia; Borsali, Redouane

    2015-01-01

    A combination of bacterial cellulose (BC) gel and amphiphilic block copolymer nanoparticles was investigated as a drug delivery system (DDS) for hydrophobic active ingredients. Poly(ethylene oxide)-b-poly(caprolactone) (PEO-b-PCL) and retinol were used as the block copolymer and hydrophobic active ingredient, respectively. The BC gel was capable of incorporating copolymer nanoparticles and releasing them in an acetic acid-sodium acetate buffer solution (pH 5.2) at 37 °C. The percentage of released copolymer reached a maximum value of approximately 60% after 6h and remained constant after 24h. The percentage of retinol released from the copolymer-containing BC gel reached a maximum value at 4h. These results show that the combination of BC gel and nanoparticles is a slow-release system that may be useful in the cosmetic and biomedical fields for skin treatment and preparation. PMID:25840273

  11. A slow-release system of bacterial cellulose gel and nanoparticles for hydrophobic active ingredients.

    PubMed

    Numata, Yukari; Mazzarino, Leticia; Borsali, Redouane

    2015-01-01

    A combination of bacterial cellulose (BC) gel and amphiphilic block copolymer nanoparticles was investigated as a drug delivery system (DDS) for hydrophobic active ingredients. Poly(ethylene oxide)-b-poly(caprolactone) (PEO-b-PCL) and retinol were used as the block copolymer and hydrophobic active ingredient, respectively. The BC gel was capable of incorporating copolymer nanoparticles and releasing them in an acetic acid-sodium acetate buffer solution (pH 5.2) at 37 °C. The percentage of released copolymer reached a maximum value of approximately 60% after 6h and remained constant after 24h. The percentage of retinol released from the copolymer-containing BC gel reached a maximum value at 4h. These results show that the combination of BC gel and nanoparticles is a slow-release system that may be useful in the cosmetic and biomedical fields for skin treatment and preparation.

  12. Alginate/chitosan nanoparticles for encapsulation and controlled release of vitamin B2.

    PubMed

    Azevedo, Maria A; Bourbon, Ana I; Vicente, António A; Cerqueira, Miguel A

    2014-11-01

    This work aims at evaluating encapsulation and controlled release of vitamin B2 from alginate/chitosan nanoparticles. Ionotropic polyelectrolyte pre-gelation was used as production method being chitosan and alginate used as main materials. Nanoparticles were characterized in terms of average size, polydispersity index (PDI), zeta potential and vitamin entrapment efficiency. The average size for alginate/chitosan nanoparticles was 119.5±49.9nm for samples without vitamin B2 and 104.0±67.2nm with the encapsulation of vitamin B2, presenting a PDI of 0.454±0.066 and 0.319±0.068, respectively. The nanoparticles showed encapsulation efficiency and loading capacity values of 55.9±5.6% and 2.2±0.6%, respectively. Release profiles were evaluated at different conditions showing that the polymeric relaxation was the most influent phenomenon in vitamin B2 release. In order to study their stability nanoparticles were stored at 4°C being particles sizes and PDI evaluated during 5 months showing the results that vitamin B2-loaded nanoparticles are more stable (in terms of size and PDI) than nanoparticles without vitamin B2.

  13. Clean Photothermal Heating and Controlled Release From Near Infrared Dye Doped Nanoparticles Without Oxygen Photosensitization

    PubMed Central

    Guha, Samit; Shaw, Scott K.; Spence, Graeme T.; Roland, Felicia M.; Smith, Bradley D.

    2015-01-01

    The photothermal heating and release properties of biocompatible organic nanoparticles, doped with a near-infrared croconaine (Croc) dye, were compared with analogous nanoparticles doped with the common near-infrared dyes ICG and IR780. Separate formulations of lipid-polymer-hybrid nanoparticles and liposomes, each containing Croc dye, absorbed strongly at 808 nm and generated clean laser-induced heating (no production of 1O2 and no photobleaching of the dye). In contrast, laser-induced heating of nanoparticles containing ICG or IR780 produced reactive 1O2 leading to bleaching of the dye and also decomposition of co-encapsulated payload such as the drug Doxorubicin. Croc dye was especially useful as a photothermal agent for laser controlled release of chemically sensitive payload from nanoparticles. Solution state experiments demonstrated repetitive fractional release of water soluble fluorescent dye from the interior of thermosensitive liposomes. Additional experiments used a focused laser beam to control leakage from immobilized liposomes with very high spatial and temporal precision. The results indicate that fractional photothermal leakage from nanoparticles doped with Croc dye is a promising method for a range of controlled release applications. PMID:26149326

  14. In vitro release and biological activities of Carum copticum essential oil (CEO) loaded chitosan nanoparticles.

    PubMed

    Esmaeili, Akbar; Asgari, Azadeh

    2015-11-01

    In recent years, the unparalleled and functional properties of essential oils have been extensively reported, but the sensitivity of essential oils to environmental factors and their poor aqueous solubility have limited their applications in industries. Hence, we encapsulated CEO in chitosan nanoparticles by an emulsion-ionic gelation with pantasodium tripolyphosphate (TPP) and sodium hexametaphosphte (HMP), separately, as crosslinkers. The nanoparticles were analyzed by Fourier transform infrared spectroscopy (FT-IR), Ultraviolet-visible spectroscopy (UV-vis), differential scanning calorimetry (DSC), scanning electron microscope (SEM) and dynamic light scattering (DLS). The encapsulation efficiency (EE) and loading capacity (LC) of CEO in chitosan nanoparticles increased with the increase of initial CEO amount. The nanoparticles displayed an average size of 30-80nm with a spherical shape and regular distribution. In vitro release profiles exhibited an initial burst release and followed by a sustained CEO release at different pH conditions. The amount of CEO release from chitosan nanoparticles was higher in acidic pH to basic or neutral pH, respectively. The biological properties of CEO, before and after the encapsulation process were evaluated by 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and agar disk diffusion method, respectively. The results indicated the encapsulation of CEO in chitosan nanoparticles could be protected the quality. PMID:26257380

  15. In vitro release and biological activities of Carum copticum essential oil (CEO) loaded chitosan nanoparticles.

    PubMed

    Esmaeili, Akbar; Asgari, Azadeh

    2015-11-01

    In recent years, the unparalleled and functional properties of essential oils have been extensively reported, but the sensitivity of essential oils to environmental factors and their poor aqueous solubility have limited their applications in industries. Hence, we encapsulated CEO in chitosan nanoparticles by an emulsion-ionic gelation with pantasodium tripolyphosphate (TPP) and sodium hexametaphosphte (HMP), separately, as crosslinkers. The nanoparticles were analyzed by Fourier transform infrared spectroscopy (FT-IR), Ultraviolet-visible spectroscopy (UV-vis), differential scanning calorimetry (DSC), scanning electron microscope (SEM) and dynamic light scattering (DLS). The encapsulation efficiency (EE) and loading capacity (LC) of CEO in chitosan nanoparticles increased with the increase of initial CEO amount. The nanoparticles displayed an average size of 30-80nm with a spherical shape and regular distribution. In vitro release profiles exhibited an initial burst release and followed by a sustained CEO release at different pH conditions. The amount of CEO release from chitosan nanoparticles was higher in acidic pH to basic or neutral pH, respectively. The biological properties of CEO, before and after the encapsulation process were evaluated by 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and agar disk diffusion method, respectively. The results indicated the encapsulation of CEO in chitosan nanoparticles could be protected the quality.

  16. Encapsulation-free controlled release: Electrostatic adsorption eliminates the need for protein encapsulation in PLGA nanoparticles

    PubMed Central

    Pakulska, Malgosia M.; Elliott Donaghue, Irja; Obermeyer, Jaclyn M.; Tuladhar, Anup; McLaughlin, Christopher K.; Shendruk, Tyler N.; Shoichet, Molly S.

    2016-01-01

    Encapsulation of therapeutic molecules within polymer particles is a well-established method for achieving controlled release, yet challenges such as low loading, poor encapsulation efficiency, and loss of protein activity limit clinical translation. Despite this, the paradigm for the use of polymer particles in drug delivery has remained essentially unchanged for several decades. By taking advantage of the adsorption of protein therapeutics to poly(lactic-co-glycolic acid) (PLGA) nanoparticles, we demonstrate controlled release without encapsulation. In fact, we obtain identical, burst-free, extended-release profiles for three different protein therapeutics with and without encapsulation in PLGA nanoparticles embedded within a hydrogel. Using both positively and negatively charged proteins, we show that short-range electrostatic interactions between the proteins and the PLGA nanoparticles are the underlying mechanism for controlled release. Moreover, we demonstrate tunable release by modifying nanoparticle concentration, nanoparticle size, or environmental pH. These new insights obviate the need for encapsulation and offer promising, translatable strategies for a more effective delivery of therapeutic biomolecules. PMID:27386554

  17. Formulating nanoparticles by flash nanoprecipitation for drug delivery and sustained release

    NASA Astrophysics Data System (ADS)

    Liu, Ying

    This dissertation provides a fundamental understanding of the process for generating nanoparticles with controlled size distribution and of predicting nanoparticle stability for drug delivery and sustained release. We developed and characterized a novel technology to generate organic and inorganic nanoparticles protected by biocompatible and biodegradable polymers with precisely controlled size and size distribution. Computational fluid mechanics (CFD) together with experimental results provided details of the micromixing in the mixer. The particle size dependence on Reynolds number and supersaturation was illustrated. The study of the fundamental mass transfer phenomena leading to Ostwald ripening enables quantitative prediction of the time evolution of nanoparticles with monodistribution and relatively broader multi-distribution using beta-carotene and polystyrene-b-poly(ethylene oxide) (PS-b-PEO) as a model system. Negatively charged latex particles were used to exam the attachment of the diblock copolymer, PS-b-PEO, on the surface. The stability provided by the Columbic repulsion was replaced by steric stabilization. The attachment of the block copolymers on the surface of the colloids depends on the flow field, i.e. Reynolds number, of the mixing process. The slow degradation of poly(epsilon-caprolactone) (PCL) and poly(gamma-methyl-epsilon-caprolactone) (PMCL) was demonstrated. The slow degradation ensures long-term stability and long-term blood circulation of the polymeric nanoparticles. As a practical application, we formulate the anti-tuberculosis drug, rifampicin, into nanoparticles by conjugation to other hydrophobic molecules (such as vitamin E, PCL and 2-ethylhexyl vinyl ether) by pH sensitive cleavable chemical bonds to increase the drug loading, return stability of the nanoparticle suspension, and control drug release. The in vitro release profiles were provided by using HPLC and E.coli growth inhibition on LB agar plates. The prodrug nanoparticle

  18. Light-induced Release of DNA from Gold Nanoparticles: Nanoshells and Nanorods

    PubMed Central

    Huschka, Ryan; Zuloaga, Jorge; Knight, Mark; Brown, Lisa V.; Nordlander, Peter; Halas, Naomi J.

    2013-01-01

    Plasmon-resonant nanoparticle complexes show highly promising potential for light-triggered, remote-controlled delivery of oligonucleotides on demand, for research and therapeutic purposes. Here we investigate the light-triggered release of DNA from two types of nanoparticle substrates: Au nanoshells and Au nanorods. Both light-triggered and thermally induced release are distinctly observable from nanoshell-based complexes, with light-triggered release occurring at an ambient solution temperature well below the DNA melting temperature. Surprisingly, no analogous measureable release was observable from nanorod-based complexes below the DNA melting temperature. These results suggest that a nonthermal mechanism may play a role in plasmon resonant, light-triggered DNA release. PMID:21736347

  19. Characterization of Nanoparticle Release from Surface Coatings by the Simulation of a Sanding Process

    PubMed Central

    Göhler, Daniel; Stintz, Michael; Hillemann, Lars; Vorbau, Manuel

    2010-01-01

    Nanoparticles are used in industrial and domestic applications to control customized product properties. But there are several uncertainties concerning possible hazard to health safety and environment. Hence, it is necessary to search for methods to analyze the particle release from typical application processes. Based on a survey of commercial sanding machines, the relevant sanding process parameters were employed for the design of a miniature sanding test setup in a particle-free environment for the quantification of the nanoparticle release into air from surface coatings. The released particles were moved by a defined airflow to a fast mobility particle sizer and other aerosol measurement equipment to enable the determination of released particle numbers additionally to the particle size distribution. First, results revealed a strong impact of the coating material on the swarf mass and the number of released particles. PMID:20696941

  20. Characterization of nanoparticle release from surface coatings by the simulation of a sanding process.

    PubMed

    Göhler, Daniel; Stintz, Michael; Hillemann, Lars; Vorbau, Manuel

    2010-08-01

    Nanoparticles are used in industrial and domestic applications to control customized product properties. But there are several uncertainties concerning possible hazard to health safety and environment. Hence, it is necessary to search for methods to analyze the particle release from typical application processes. Based on a survey of commercial sanding machines, the relevant sanding process parameters were employed for the design of a miniature sanding test setup in a particle-free environment for the quantification of the nanoparticle release into air from surface coatings. The released particles were moved by a defined airflow to a fast mobility particle sizer and other aerosol measurement equipment to enable the determination of released particle numbers additionally to the particle size distribution. First, results revealed a strong impact of the coating material on the swarf mass and the number of released particles.

  1. Fabrication of porous hollow silica nanoparticles and their applications in drug release control.

    PubMed

    Li, Zhu-Zhu; Wen, Li-Xiong; Shao, Lei; Chen, Jian-Feng

    2004-08-11

    Preparation and characterization of porous hollow silica nanoparticles (PHSN) for controlled release applications were investigated. Through orthogonally designed experiments, the optimal synthesis conditions for the preparation of PHSN were obtained and the produced PHSN were characterized by BET, SEM, TEM and IR. Scanning and transmission electron microscopy images revealed their hollow shell-core structure and also demonstrated that the size and shape of PHSN are determined by the templating CaCO3 nanoparticles. The produced PHSN were applied as a carrier to study the controlled release behaviors of Brilliant Blue F (BB), which was used as a model drug. Being loaded into the inner core and on the surfaces of the nanoparticles, BB was released slowly into a bulk solution for about 1140 min as compared to only 10 min for the normal SiO2 nanoparticles, thus exhibited a typical sustained release pattern without any burst effect. In addition, higher BET of the carriers, lower pH value and lower temperature prolonged BB release from PHSN, while stirring speed showed little influence on the release behavior. It showed that PHSN have a promising future in controlled drug delivery applications.

  2. Voltage/pH-Driven Mechanized Silica Nanoparticles for the Multimodal Controlled Release of Drugs.

    PubMed

    Wang, Ting; Sun, GuangPing; Wang, MingDong; Zhou, BaoJing; Fu, JiaJun

    2015-09-30

    The major challenges of current drug delivery systems for combination chemotherapy focus on how to efficiently transport drugs to target sites and release multiple drugs in a programmed manner. Herein, we report a novel multidrug delivery system, MSNPs 1, based on mechanized silica nanoparticles, which were constructed through functionalization of mesoporous silica nanoparticles with the acid-cleavable intermediate linkages and the monoferrocene functionalized β-cyclodextrin (Fc-β-CD) as supramolecular nanovalves. MSNPs 1 achieved zero premature release in the physiological pH solution and realized two different release modalities. In modality 1, MSNPs 1 released the encapsulated drugs gemcitabine (GEM) and doxorubicin (DOX) in sequence when they were successively applied to voltage and acid stimuli. The release time and dosage of GEM were precisely controlled via external voltage. The subsequent acid-triggered release of DOX was attributed to breakage of the intermediate linkages containing ketal groups. Modality 2 is the concurrent release of these two drugs directly upon acid exposure. Furthermore, the cell viability experiments demonstrated that MSNPs 1 had an improved cytotoxicity to MCF7 cells in comparison with single DOX- or GEM-loaded mechanized silica nanoparticles. We envisage that MSNPs 1 will play an important role in research and development for a new generation of controlled-release drug delivery system. PMID:26345470

  3. Role of size and shape on biofilm eradication for nitric oxide-releasing silica nanoparticles.

    PubMed

    Slomberg, Danielle L; Lu, Yuan; Broadnax, Angela D; Hunter, Rebecca A; Carpenter, Alexis W; Schoenfisch, Mark H

    2013-10-01

    Nitric oxide (NO), a reactive free radical, has proven effective in eradicating bacterial biofilms with reduced risk of fostering antibacterial resistance. Herein, we evaluated the efficacy of NO-releasing silica nanoparticles against Gram-negative Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus biofilms as a function of particle size and shape. Three sizes of NO-releasing silica nanoparticles (i.e., 14, 50, and 150 nm) with identical total NO release (∼0.3 μmol/mg) were utilized to study antibiofilm eradication as a function of size. To observe the role of particle shape on biofilm killing, we varied the aspect ratio of the NO-releasing silica particles from 1 to 8 while maintaining constant particle volume (∼0.02 μm(3)) and NO-release totals (∼0.7 μmol/mg). Nitric oxide-releasing particles with decreased size and increased aspect ratio were more effective against both P. aeruginosa and S. aureus biofilms, with the Gram-negative species exhibiting the greatest susceptibility to NO. To further understand the influence of these nanoparticle properties on NO-mediated antibacterial activity, we visualized intracellular NO concentrations and cell death with confocal microscopy. Smaller NO-releasing particles (14 nm) exhibited better NO delivery and enhanced bacteria killing compared to the larger (50 and 150 nm) particles. Likewise, the rod-like NO-releasing particles proved more effective than spherical particles in delivering NO and inducing greater antibacterial action throughout the biofilm.

  4. Calcium and phosphate release from resin-based materials containing different calcium orthophosphate nanoparticles.

    PubMed

    Rodrigues, Marcela C; Natale, Livia C; Arana-Chaves, Victor E; Braga, Roberto R

    2015-11-01

    The study compared ion release from resin-based materials containing calcium orthophosphates. Amorphous calcium phosphate (ACP), dicalcium phosphate anhydrous (DCPA), dicalcium phosphate dihydrate (DCPD), and tricalcium phosphate (β-TCP) nanoparticles were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), dynamic light scattering (DLS), and surface area (nitrogen adsorption isotherms, BET method). Nanoparticles were added to a dimethacrylate-based resin and materials were tested for degree of conversion (DC) and calcium/phosphate release up to 28 days under pH 5.5 and 7.0. Data were analyzed by ANOVA/Tukey test (alpha: 0.05).The crystallinity of DCPA, DCPD, and β-TCP were confirmed, as well as the ACP amorphous nature. DCPD and β-TCP presented larger agglomerates than DCPA and ACP. The surface area of ACP was 5-11 times higher than those of the other nanoparticles. Materials showed similar DC. The material containing ACP released significantly more ions than the others, which released similar amounts of calcium and, in most cases, phosphate. Ion release was not affected by pH. Calcium release decreased between 7 and 21 days, while phosphate levels remained constant after 14 days. In conclusion, ACP higher ion release can be ascribed to its high surface area. DCPA, DCPD, and β-TCP had similar performances as ion-releasing fillers.

  5. Controlling phosphate releasing from poultry litter using stabilized Fe-Mn binary oxide nanoparticles.

    PubMed

    Xie, Wenbo; Zhao, Dongye

    2016-01-15

    Animal wastes contain high concentrations of phosphorus (P), most of which is lost into the environment due to uncontrolled release rates. Polysaccharide stabilized Fe-Mn binary oxide nanoparticles were prepared and tested for phosphate adsorption from water and for controlling leachability of P from poultry litter. A water soluble starch and carboxymethyl cellulose (CMC) were used as a stabilizer. Both the Freundlich and Langmuir models were able to adequately interpret the isotherm data. The Langmuir maximum capacity was determined at 252, 298 and 313 mg-P/g for bare, CMC- and starch-stabilized nanoparticles, respectively. The presence of the stabilizers not only enhanced the sorption capacity, but facilitated delivery and dispersion of the nanoparticles in poultry litter (PL) and in soil. High phosphate sorption capacity was observed over a broad pH range of 4-9. FTIR analyses indicated that inner sphere surface complexation (Fe-O-P) was the key mechanism for the enhanced uptake of P. When applied to poultry litter, the stabilized nanoparticles reduced water leachable phosphate by >86% at a dose of 0.2 g/L as Fe, and simultaneously, water leachable arsenic by >87-95%. Under conditions of simulated land application of PL, the nanoparticle amendment of PL reduced the water soluble P from 66% (for untreated PL) to 4.4%, and lowered the peak soluble P concentration from 300 to <20 mg/L. By transferring the peak soluble P to the nanoparticle-bound P, the nanoparticles not only greatly reduce the potential runoff loss of P from PL, but also provide a long-term slow-releasing nutrient source. Fortuitously, the nanoparticle treatment was able to immobilize arsenic from PL. With excellent adsorption capacity, easy deliverability, low cost and environmental innocuousness, the stabilized Fe-Mn nanoparticles appear promising for controlling P releases from poultry litter or other animal wastes and for phosphate recovery from water. PMID:26442720

  6. Cubic phase nanoparticles for sustained release of ibuprofen: formulation, characterization, and enhanced bioavailability study

    PubMed Central

    Dian, Linghui; Yang, Zhiwen; Li, Feng; Wang, Zhouhua; Pan, Xin; Peng, Xinsheng; Huang, Xintian; Guo, Zhefei; Quan, Guilan; Shi, Xuan; Chen, Bao; Li, Ge; Wu, Chuanbin

    2013-01-01

    In order to improve the oral bioavailability of ibuprofen, ibuprofen-loaded cubic nanoparticles were prepared as a delivery system for aqueous formulations. The cubic inner structure was verified by cryogenic transmission electron microscopy. With an encapsulation efficiency greater than 85%, the ibuprofen-loaded cubic nanoparticles had a narrow size distribution around a mean size of 238 nm. Differential scanning calorimetry and X-ray diffraction determined that ibuprofen was in an amorphous and molecular form within the lipid matrix. The in vitro release of ibuprofen from cubic nanoparticles was greater than 80% at 24 hours, showing sustained characteristics. The pharmacokinetic study in beagle dogs showed improved absorption of ibuprofen from cubic nanoparticles compared to that of pure ibuprofen, with evidence of a longer half-life and a relative oral bioavailability of 222% (P < 0.05). The ibuprofen-loaded cubic nanoparticles provide a promising carrier candidate with an efficient drug delivery for therapeutic treatment. PMID:23468008

  7. A dynamic topical hydrofluoroalkane foam to induce nanoparticle modification and drug release in situ.

    PubMed

    Zhao, Yanjun; Moddaresi, Mojgan; Jones, Stuart A; Brown, Marc B

    2009-08-01

    Topical nanoparticles are usually applied using semi-solid formulations, but the delivery process is often inefficient due to the poor drug release from the particles. The aim of this study was to investigate the capability of a dynamic foam to break open nanoparticles upon application to the skin and enhance drug delivery efficiency. Vitamin E acetate (VEAc) was selected as a model drug and loaded into lipid nanoparticles (50-60 nm) prepared by phase inversion. The highest drug loading was 18.9+/-1.2 mg/ml and the corresponding encapsulation efficiency was 81.5+/-4.1%. Dynamic foams were generated by emulsifying VEAc-loaded nanoparticle suspensions with hydrofluoroalkane using pluronic L62D. An in vitro permeation study demonstrated that VEAc did not release from the nanoparticles when administered as an aqueous suspension, but attained a flux of 18.0+/-2.1 (microg cm(-2) h(-1)) when applied using the foam. Drug release from the foam was shown to be a consequence of nanoparticle modification after dose administration and this led to the foam delivering 0.7+/-0.3% VEAc into the stratum corneum (SC) when applied to human skin.

  8. Nanoparticles Containing High Loads of Paclitaxel-Silicate Prodrugs: Formulation, Drug Release, and Anticancer Efficacy.

    PubMed

    Han, Jing; Michel, Andrew R; Lee, Han Seung; Kalscheuer, Stephen; Wohl, Adam; Hoye, Thomas R; McCormick, Alon V; Panyam, Jayanth; Macosko, Christopher W

    2015-12-01

    We have investigated particle size, interior structure, drug release kinetics, and anticancer efficacy of PEG-b-PLGA-based nanoparticles loaded with a series of paclitaxel (PTX)-silicate prodrugs [PTX-Si(OR)3]. Silicate derivatization enabled us to adjust the hydrophobicity and hydrolytic lability of the prodrugs by the choice of the alkyl group (R) in the silicate derivatives. The greater hydrophobicity of these prodrugs allows for the preparation of nanoparticles that are stable in aqueous dispersion even when loaded with up to ca. 75 wt % of the prodrug. The hydrolytic lability of silicates allows for facile conversion of prodrugs back to the parent drug, PTX. A suite of eight PTX-silicate prodrugs was investigated; nanoparticles were made by flash nanoprecipitation (FNP) using a confined impingement jet mixer with a dilution step (CIJ-D). The resulting nanoparticles were 80-150 nm in size with a loading level of 47-74 wt % (wt %) of a PTX-silicate, which corresponds to 36-59 effective wt % of free PTX. Cryogenic transmission electron microscopy images show that particles are typically spherical with a core-shell structure. Prodrug/drug release profiles were measured. Release tended to be slower for prodrugs having greater hydrophobicity and slower hydrolysis rate. Nanoparticles loaded with PTX-silicate prodrugs that hydrolyze most rapidly showed in vitro cytotoxicity similar to that of the parent PTX. Nanoparticles loaded with more labile silicates also tended to show greater in vivo efficacy. PMID:26505116

  9. Nanoparticles Containing High Loads of Paclitaxel-Silicate Prodrugs: Formulation, Drug Release, and Anticancer Efficacy.

    PubMed

    Han, Jing; Michel, Andrew R; Lee, Han Seung; Kalscheuer, Stephen; Wohl, Adam; Hoye, Thomas R; McCormick, Alon V; Panyam, Jayanth; Macosko, Christopher W

    2015-12-01

    We have investigated particle size, interior structure, drug release kinetics, and anticancer efficacy of PEG-b-PLGA-based nanoparticles loaded with a series of paclitaxel (PTX)-silicate prodrugs [PTX-Si(OR)3]. Silicate derivatization enabled us to adjust the hydrophobicity and hydrolytic lability of the prodrugs by the choice of the alkyl group (R) in the silicate derivatives. The greater hydrophobicity of these prodrugs allows for the preparation of nanoparticles that are stable in aqueous dispersion even when loaded with up to ca. 75 wt % of the prodrug. The hydrolytic lability of silicates allows for facile conversion of prodrugs back to the parent drug, PTX. A suite of eight PTX-silicate prodrugs was investigated; nanoparticles were made by flash nanoprecipitation (FNP) using a confined impingement jet mixer with a dilution step (CIJ-D). The resulting nanoparticles were 80-150 nm in size with a loading level of 47-74 wt % (wt %) of a PTX-silicate, which corresponds to 36-59 effective wt % of free PTX. Cryogenic transmission electron microscopy images show that particles are typically spherical with a core-shell structure. Prodrug/drug release profiles were measured. Release tended to be slower for prodrugs having greater hydrophobicity and slower hydrolysis rate. Nanoparticles loaded with PTX-silicate prodrugs that hydrolyze most rapidly showed in vitro cytotoxicity similar to that of the parent PTX. Nanoparticles loaded with more labile silicates also tended to show greater in vivo efficacy.

  10. Evaluation of the effects of nitric oxide-releasing nanoparticles on plants

    NASA Astrophysics Data System (ADS)

    Pereira, A. E. S.; Narciso, A. M.; Seabra, A. B.; Fraceto, L. F.

    2015-05-01

    Nowadays, there are several commercially available products containing nanostructured materials. Meanwhile, despite the many benefits that can be obtained from nanotechnology, it is still necessary to understand the mechanisms in which nanomaterials interact with the environment, and to obtain information concerning their possible toxic effects. In agriculture, nanotechnology has been used in different applications, such as nanosensors to detect pathogens, nanoparticles as controlled release systems for pesticides, and biofilms to deliver nutrients to plants and to protect food products against degradation. Moreover, plants can be used as models to study the toxicity of nanoparticles. Indeed, phytotoxicity assays are required to identify possible negative effects of nanostructured systems, prior to their implementation in agriculture. Nitric oxide (NO) plays a key role in plant growth and defense, and recently, several papers described the beneficial effects due to application of exogenous NO donors in plants. The tripeptide glutathione (GSH) is an important anti-oxidant molecule and is the precursor of the NO donor, S-nitrosoglutathione (GSNO). In this context, the present work investigates the effects of different concentrations of alginate/chitosan nanoparticles, containing either GSH or GSNO, on the development of two test species (Zea mays and Glycine sp.). The results showed that the alginate/chitosan nanoparticles present a size average range from 300 to 550 nm with a polydispersity index of 0.35, and encapsulation efficiency of GSH between 45 - 56%. The NO release kinetics from the alginate/chitosan nanoparticles containing GSNO showed sustained and controlled NO release over several hours. Plant assays showed that at the concentrations tested (1, 5 and 10 mM of GSH or GSNO), polymeric nanoparticles showed no significant inhibitory effects on the development of the species Zea mays and Glycine sp., considering the variables shoot height, root length, and

  11. Controlled drug release and hydrolysis mechanism of polymer-magnetic nanoparticle composite.

    PubMed

    Yang, Fang; Zhang, Xiaoxian; Song, Lina; Cui, Huating; Myers, John N; Bai, Tingting; Zhou, Ying; Chen, Zhan; Gu, Ning

    2015-05-13

    Uniform and multifunctional poly(lactic acid) (PLA)-nanoparticle composite has enormous potential for applications in biomedical and materials science. A detailed understanding of the surface and interface chemistry of these composites is essential to design such materials with optimized function. Herein, we designed and investigated a simple PLA-magnetic nanoparticle composite system to elucidate the impact of nanoparticles on the degradation of polymer-nanoparticle composites. In order to have an in-depth understanding of the mechanisms of hydrolysis in PLA-nanoparticle composites, degradation processes were monitored by several surface sensitive techniques, including scanning electron microscopy, contact angle goniometry, atomic force microscopy, and sum frequency generation spectroscopy. As a second-order nonlinear optical technique, SFG spectroscopy was introduced to directly probe in situ chemical nature at the PLA-magnetic nanoparticle composite/aqueous interface, which allowed for the delineation of molecular mechanisms of various hydrolysis processes for degradation at the molecular level. The best PLA-NP material, with a concentration of 20% MNP in the composite, was found to enhance the drug release rate greater than 200 times while maintaining excellent controlled drug release characteristics. It was also found that during hydrolysis, various crystalline-like PLA domains on the surfaces of PLA-nanoparticle composites influenced various hydrolysis behaviors of PLA. Results from this study provide new insight into the design of nanomaterials with controlled degradation and drug release properties, and the underlined molecular mechanisms. The methodology developed in this study to characterize the polymer-nanoparticle composites is general and widely applicable.

  12. Controlled drug release and hydrolysis mechanism of polymer-magnetic nanoparticle composite.

    PubMed

    Yang, Fang; Zhang, Xiaoxian; Song, Lina; Cui, Huating; Myers, John N; Bai, Tingting; Zhou, Ying; Chen, Zhan; Gu, Ning

    2015-05-13

    Uniform and multifunctional poly(lactic acid) (PLA)-nanoparticle composite has enormous potential for applications in biomedical and materials science. A detailed understanding of the surface and interface chemistry of these composites is essential to design such materials with optimized function. Herein, we designed and investigated a simple PLA-magnetic nanoparticle composite system to elucidate the impact of nanoparticles on the degradation of polymer-nanoparticle composites. In order to have an in-depth understanding of the mechanisms of hydrolysis in PLA-nanoparticle composites, degradation processes were monitored by several surface sensitive techniques, including scanning electron microscopy, contact angle goniometry, atomic force microscopy, and sum frequency generation spectroscopy. As a second-order nonlinear optical technique, SFG spectroscopy was introduced to directly probe in situ chemical nature at the PLA-magnetic nanoparticle composite/aqueous interface, which allowed for the delineation of molecular mechanisms of various hydrolysis processes for degradation at the molecular level. The best PLA-NP material, with a concentration of 20% MNP in the composite, was found to enhance the drug release rate greater than 200 times while maintaining excellent controlled drug release characteristics. It was also found that during hydrolysis, various crystalline-like PLA domains on the surfaces of PLA-nanoparticle composites influenced various hydrolysis behaviors of PLA. Results from this study provide new insight into the design of nanomaterials with controlled degradation and drug release properties, and the underlined molecular mechanisms. The methodology developed in this study to characterize the polymer-nanoparticle composites is general and widely applicable. PMID:25881356

  13. Modulating in vitro release and solubility of griseofulvin using functionalized mesoporous silica nanoparticles.

    PubMed

    Jambhrunkar, Siddharth; Qu, Zhi; Popat, Amirali; Karmakar, Surajit; Xu, Chun; Yu, Chengzhong

    2014-11-15

    Mesoporous silica nanoparticles (MCM-41) were used as a carrier system to study the influence of surface charge and hydrophobicity on solubility and in-vitro drug release behavior of Griseofulvin, a potent antifungal drug with low water solubility. Bare MCM-41 with a pure silica composition, MCM-41 after amino functionalization (MCM-41-NH2) and methyl functionalization (MCM-41-CH3) were used in this study followed by encapsulation of griseofulvin. Various characterization techniques have been employed to confirm the successful drug loading inside the nanopores. The surface functionalization on MCM-41 is found to have significant effect on griseofulvin's in vitro release and solubility. Both negatively and positively charged surface showed enhancement in solubility and drug release of griseofulvin. However, the hydrophobic modification led to a retarded drug release, which is caused by the poor wetting effect in the case of MCM-41-CH3 nanoparticles.

  14. Antimicrobial and wound healing properties of nitric oxide-releasing xerogels and silica nanoparticles

    NASA Astrophysics Data System (ADS)

    Hetrick, Evan M.

    Indwelling medical devices continue to be plagued by the body's response to foreign materials and the ever-present threat of microbial infection. Endogenously-produced nitric oxide (NO) has been shown to play beneficial roles in both wound healing and the body's defense against infection. To exploit NO's favorable properties for biomaterials applications, previous studies have detailed the synthesis of xerogel polymers and silica nanoparticles capable of storing and releasing NO via diazeniumdiolate NO-donors. Here, the ability of NO-releasing materials to reduce bacterial adhesion under flow conditions, modulate the foreign body response, and kill microbial pathogens is described. To more thoroughly characterize the antibacterial properties of NO-releasing xerogels, studies were conducted with Pseudomonas aeruginosa in a parallel plate flow cell. Xerogels modified to release NO reduced bacterial adhesion in a flux-dependent manner, with a NO flux of ˜21 pmol·cm -2·s-1 inhibiting P. aeruginosa adhesion by 65% compared to controls. Fluorescent viability probes indicated that bacteria adhered to NO-releasing xerogels were killed within 7 h of adhesion. In terms of tissue biocompatibility, the foreign body response was studied in an animal model at the site of subcutaneous implants coated with NO-releasing xerogels. Implant-derived NO reduced capsule thickness and the chronic inflammatory response by 50 and 30%, respectively, compared to controls. Additionally, 77% more blood vessels were observed in proximity to NO-releasing implants after 1 week compared to controls. Along with their ability to reduce bacterial adhesion and mitigate the foreign body response, NO-releasing materials may prove useful for treating infections due to the broad-spectrum antimicrobial properties of NO. Recently, silica nanoparticles have been developed that release micromolar quantities of NO, and here the efficacy of such nanoparticles was examined against both planktonic and biofilm

  15. NMR cryoporometry characterisation studies of the relation between drug release profile and pore structural evolution of polymeric nanoparticles.

    PubMed

    Gopinathan, Navin; Yang, Bin; Lowe, John P; Edler, Karen J; Rigby, Sean P

    2014-07-20

    PLGA/PLA polymeric nanoparticles could potentially enhance the effectiveness of convective delivery of drugs, such as carboplatin, to the brain, by enabling a more sustained dosage over a longer time than otherwise possible. However, the link between the controlled release nanoparticle synthesis route, and the subsequent drug release profile obtained, is not well-understood, which hinders design of synthesis routes and availability of suitable nanoparticles. In particular, despite pore structure evolution often forming a key aspect of past theories of the physical mechanism by which a particular drug release profile is obtained, these theories have not been independently tested and validated against pore structural information. Such validation is required for intelligent synthesis design, and NMR cryoporometry can supply the requisite information. Unlike conventional pore characterisation techniques, NMR cryoporometry permits the investigation of porous particles in the wet state. NMR cryoporometry has thus enabled the detailed study of the evolving, nanoscale structure of nanoparticles during drug release, and thus related pore structure to drug release profile in a way not done previously for nanoparticles. Nanoparticles with different types of carboplatin drug release profiles were compared, including burst release, and various forms of delayed release. ESEM and TEM images of these nanoparticles also provided supporting data showing the rapid initial evolution of some nanoparticles. Different stages, within a complex, varying drug release profile, were found to be associated with particular types of changes in the nanostructure which could be distinguished by NMR. For a core-coat nanoparticle formulation, the development of smaller nanopores, following an extended induction period with no structural change, was associated with the onset of substantial drug release. This information could be used to independently validate the rationale for a particular synthesis

  16. NMR cryoporometry characterisation studies of the relation between drug release profile and pore structural evolution of polymeric nanoparticles.

    PubMed

    Gopinathan, Navin; Yang, Bin; Lowe, John P; Edler, Karen J; Rigby, Sean P

    2014-07-20

    PLGA/PLA polymeric nanoparticles could potentially enhance the effectiveness of convective delivery of drugs, such as carboplatin, to the brain, by enabling a more sustained dosage over a longer time than otherwise possible. However, the link between the controlled release nanoparticle synthesis route, and the subsequent drug release profile obtained, is not well-understood, which hinders design of synthesis routes and availability of suitable nanoparticles. In particular, despite pore structure evolution often forming a key aspect of past theories of the physical mechanism by which a particular drug release profile is obtained, these theories have not been independently tested and validated against pore structural information. Such validation is required for intelligent synthesis design, and NMR cryoporometry can supply the requisite information. Unlike conventional pore characterisation techniques, NMR cryoporometry permits the investigation of porous particles in the wet state. NMR cryoporometry has thus enabled the detailed study of the evolving, nanoscale structure of nanoparticles during drug release, and thus related pore structure to drug release profile in a way not done previously for nanoparticles. Nanoparticles with different types of carboplatin drug release profiles were compared, including burst release, and various forms of delayed release. ESEM and TEM images of these nanoparticles also provided supporting data showing the rapid initial evolution of some nanoparticles. Different stages, within a complex, varying drug release profile, were found to be associated with particular types of changes in the nanostructure which could be distinguished by NMR. For a core-coat nanoparticle formulation, the development of smaller nanopores, following an extended induction period with no structural change, was associated with the onset of substantial drug release. This information could be used to independently validate the rationale for a particular synthesis

  17. NMR cryoporometry characterisation studies of the relation between drug release profile and pore structural evolution of polymeric nanoparticles

    PubMed Central

    Gopinathan, Navin; Yang, Bin; Lowe, John P.; Edler, Karen J.; Rigby, Sean P.

    2014-01-01

    PLGA/PLA polymeric nanoparticles could potentially enhance the effectiveness of convective delivery of drugs, such as carboplatin, to the brain, by enabling a more sustained dosage over a longer time than otherwise possible. However, the link between the controlled release nanoparticle synthesis route, and the subsequent drug release profile obtained, is not well-understood, which hinders design of synthesis routes and availability of suitable nanoparticles. In particular, despite pore structure evolution often forming a key aspect of past theories of the physical mechanism by which a particular drug release profile is obtained, these theories have not been independently tested and validated against pore structural information. Such validation is required for intelligent synthesis design, and NMR cryoporometry can supply the requisite information. Unlike conventional pore characterisation techniques, NMR cryoporometry permits the investigation of porous particles in the wet state. NMR cryoporometry has thus enabled the detailed study of the evolving, nanoscale structure of nanoparticles during drug release, and thus related pore structure to drug release profile in a way not done previously for nanoparticles. Nanoparticles with different types of carboplatin drug release profiles were compared, including burst release, and various forms of delayed release. ESEM and TEM images of these nanoparticles also provided supporting data showing the rapid initial evolution of some nanoparticles. Different stages, within a complex, varying drug release profile, were found to be associated with particular types of changes in the nanostructure which could be distinguished by NMR. For a core-coat nanoparticle formulation, the development of smaller nanopores, following an extended induction period with no structural change, was associated with the onset of substantial drug release. This information could be used to independently validate the rationale for a particular synthesis

  18. Polymeric and Solid Lipid Nanoparticles for Sustained Release of Carbendazim and Tebuconazole in Agricultural Applications

    PubMed Central

    Campos, Estefânia Vangelie Ramos; Oliveira, Jhones Luiz de; da Silva, Camila Morais Gonçalves; Pascoli, Mônica; Pasquoto, Tatiane; Lima, Renata; Abhilash, P. C.; Fernandes Fraceto, Leonardo

    2015-01-01

    Carbendazim (MBC) (methyl-2-benzimidazole carbamate) and tebuconazole (TBZ) ((RS)-1-(4-chlorophenyl)-4,4-dimethyl-3-(1H-1,2,4-triazol-1-ylmethyl)pentan-3-ol) are widely used in agriculture for the prevention and control of fungal diseases. Solid lipid nanoparticles and polymeric nanocapsules are carrier systems that offer advantages including changes in the release profiles of bioactive compounds and their transfer to the site of action, reduced losses due to leaching or degradation, and decreased toxicity in the environment and humans. The objective of this study was to prepare these two types of nanoparticle as carrier systems for a combination of TBZ and MBC, and then investigate the release profiles of the fungicides as well as the stabilities and cytotoxicities of the formulations. Both nanoparticle systems presented high association efficiency (>99%), indicating good interaction between the fungicides and the nanoparticles. The release profiles of MBC and TBZ were modified when the compounds were loaded in the nanoparticles, and cytotoxicity assays showed that encapsulation of the fungicides decreased their toxicity. These fungicide systems offer new options for the treatment and prevention of fungal diseases in plants. PMID:26346969

  19. Effect of the microencapsulation of nanoparticles on the reduction of burst release.

    PubMed

    Hasan, A Sheikh; Socha, M; Lamprecht, A; Ghazouani, F El; Sapin, A; Hoffman, M; Maincent, P; Ubrich, N

    2007-11-01

    The initial burst release is one of the major problems in the development of controlled release formulations including drug-loaded micro- and nanoparticles, especially with low molecular weight drugs. The objective of the present work was to encapsulate, by the W/O/W emulsion, polymeric nanoparticles into polymeric microparticles by using non-water soluble polymers and appropriate organic solvents for the preparation of these composite microparticles. They were characterized in vitro (encapsulation efficiency, mean diameter and release kinetics) and compared with nanoparticles and classical microparticles prepared by the same method. Poly-epsilon-caprolactone (PCL) dissolved in methylene chloride was used to make nanoparticles, whereas ethylcellulose and Eudragit RS dissolved in ethyl acetate, a non-solvent of poly-epsilon-caprolactone, were used for the preparation of microparticles. Ibuprofen and triptorelin acetate were chosen as lipophilic and hydrophilic model drugs, respectively. High entrapment efficiencies were obtained with ibuprofen whereas lower amounts of triptorelin acetate were encapsulated, mainly with formulations prepared with poly-epsilon-caprolactone and Eudragit RS used alone or blended with ethylcellulose. The burst was significantly lower with composite microparticles and may be explained by the slower diffusion of the drugs through the double polymeric wall formed by the nanoparticle matrix followed by another diffusion step through the microparticle polymeric wall.

  20. Polymeric and Solid Lipid Nanoparticles for Sustained Release of Carbendazim and Tebuconazole in Agricultural Applications

    NASA Astrophysics Data System (ADS)

    Campos, Estefânia Vangelie Ramos; Oliveira, Jhones Luiz De; da Silva, Camila Morais Gonçalves; Pascoli, Mônica; Pasquoto, Tatiane; Lima, Renata; Abhilash, P. C.; Fernandes Fraceto, Leonardo

    2015-09-01

    Carbendazim (MBC) (methyl-2-benzimidazole carbamate) and tebuconazole (TBZ) ((RS)-1-(4-chlorophenyl)-4,4-dimethyl-3-(1H-1,2,4-triazol-1-ylmethyl)pentan-3-ol) are widely used in agriculture for the prevention and control of fungal diseases. Solid lipid nanoparticles and polymeric nanocapsules are carrier systems that offer advantages including changes in the release profiles of bioactive compounds and their transfer to the site of action, reduced losses due to leaching or degradation, and decreased toxicity in the environment and humans. The objective of this study was to prepare these two types of nanoparticle as carrier systems for a combination of TBZ and MBC, and then investigate the release profiles of the fungicides as well as the stabilities and cytotoxicities of the formulations. Both nanoparticle systems presented high association efficiency (>99%), indicating good interaction between the fungicides and the nanoparticles. The release profiles of MBC and TBZ were modified when the compounds were loaded in the nanoparticles, and cytotoxicity assays showed that encapsulation of the fungicides decreased their toxicity. These fungicide systems offer new options for the treatment and prevention of fungal diseases in plants.

  1. Release of ceria nanoparticles grafted on hybrid organic-inorganic films for biomedical application.

    PubMed

    Pinna, Alessandra; Figus, Cristiana; Lasio, Barbara; Piccinini, Massimo; Malfatti, Luca; Innocenzi, Plinio

    2012-08-01

    The controlled release of nanoparticles from a hybrid organic-inorganic surface allows for developing several applications based on a slow delivery of oxygen scavengers into specific environments. We have successfully grafted ceria nanoparticles on a hybrid film surface and tested their release in a buffer solution; the tests have shown that the particles are continuously delivered within a time scale of hours. The hybrid film has been synthesized using 3-glycidoxypropyltrimethoxysilane as precursor alkoxide; the synthesis has been performed in highly basic conditions to control the polycondensation reactions of both organic and inorganic networks via controlled aging of the solution. Only films prepared from aged solutions are able to graft ceria nanoparticles on their surface. The ceria nanoparticles have been characterized by X-ray diffraction, transmission electron microscopy and UV-vis spectroscopy, the hybrid films have been analyzed by Fourier transform infrared spectroscopy, atomic force microscopy and Raman spectroscopy. Raman imaging has been used for the release test. The hybrid film-ceria nanoparticles system fulfils the requirements of optical transparency and stability in buffer solutions which are necessary for biomedical applications.

  2. A Novel Microbubble Capable of Ultrasound-Triggered Release of Drug-Loaded Nanoparticles.

    PubMed

    Wang, Jiayu; Li, Pan; Tian, Rui; Hu, Wenjing; Zhang, Yuxia; Yuan, Pei; Tang, Yalan; Jia, Yuntao; Zhang, Liangke

    2016-03-01

    Drug-loaded microbubbles have shown attractive potential in disease treatment applications. The present work presents a unique ultrasound (US)-triggered system in which drug-loaded nanoparticles and perfluorocarbon gas are encapsulated within the internal space of microbubbles. The prepared curcumin-loaded albumin nanoparticle payload microbubbles (CcmANP-MB) exhibited a mean diameter of 4895.1 nm ± 421.2 nm and a drug-loading efficiency of 2.23% ± 0.08% (297% increase compared with the drug loading of common drug-loaded microbubbles). US allowed the release of the internal payload. In vitro US-triggered drug release experiments showed that the drug release of CcmANP-MB was delayed by lipid membranes and significantly increased after sonication. In vitro and in vivo US imaging experiments demonstrated that CcmANP-MB evidently enhances US imaging, which indicates that the microbubbles possess good acoustic properties even after encapsulation of nanoparticles. Tumor bearing mice were administered with CcmANP-MB through the tail vein and were then exposed to ultrasound, which resulted in an enhanced drug accumulation in tumor tissues and a significant increase in tumor growth inhibition rate (57.1%) compared with CcmANP-MB alone (28.8%) as well as curcumin-loaded albumin nanoparticle (26.2%). Therefore, the combination of lecithin microbubbles and albumin nanoparticles provides a platform for targeted drug delivery in clinical therapy and disease diagnosis. PMID:27280249

  3. Silk fibroin nanoparticles prepared by electrospray as controlled release carriers of cisplatin.

    PubMed

    Qu, Jing; Liu, Yu; Yu, Yanni; Li, Jing; Luo, Jingwan; Li, Mingzhong

    2014-11-01

    To maintain the anti-tumor activity of cis-dichlorodiamminoplatinum (CDDP) while avoiding its cytotoxicity and negative influence on normal tissue, CDDP-loaded silk fibroin nanoparticles approximately 59 nm in diameter were successfully prepared by electrospray without using organic solvent. CDDP was incorporated into nanoparticles through metal-polymer coordination bond exchange. In vitro release tests showed that the cisplatin in the nanoparticles could be slowly and sustainably released for more than 15 days. In vitro anti-cancer experiments and intracellular Pt content testing indicated that CDDP-loaded silk fibroin nanoparticles were easily internalized by A549 lung cancer cells, transferring CDDP into cancer cells and then triggering their apoptosis. In contrast, the particles were not easily internalized by L929 mouse fibroblast cells and hence showed weaker cell growth inhibition. The CDDP-loaded silk fibroin nanoparticles showed sustained and efficient killing of tumor cells but weaker inhibition of normal cells. In general, this study provides not only a novel method for preparing CDDP-loaded silk fibroin nanoparticles but also a new carrier system for clinical therapeutic drugs against lung cancers and other tumors.

  4. Dual Action Antimicrobials: Nitric Oxide Release from Quaternary Ammonium-Functionalized Silica Nanoparticles

    PubMed Central

    Carpenter, Alexis W.; Worley, Brittany V.; Slomberg, Danielle L.; Schoenfisch, Mark H.

    2012-01-01

    The synthesis of quaternary ammonium (QA)-functionalized silica nanoparticles with and without nitric oxide (NO) release capabilities is described. Glycidyltrialkylammonium chlorides of varied alkyl chain lengths (i.e., methyl, butyl, octyl, and dodecyl) were tethered to the surface of amine-containing silica nanoparticles via a ring-opening reaction. Secondary amines throughout the particle were then functionalized with N-diazeniumdiolates NO donors to yield dual functional nanomaterials with surface QAs and total NO payloads of ca. 0.3 μmol/mg. The bactericidal activities of singly (i.e., only NO-releasing or only QA-functionalized) and dual (i.e., NO-releasing and QA-functionalized) functional nanoparticles were tested against Grampositive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa. Particles with only NO release capabilities alone were found to be more effective against P. aeruginosa, while particles with only QA-functionalities exhibited greater toxicity toward S. aureus. The minimum bactericidal concentrations (MBC) of QA-functionalized particles decreased with increasing alkyl chain length against both microbes tested. Combining NO release and QA-functionalities on the same particle resulted in an increase in bactericidal efficacy against S. aureus; however, no change in activity against P. aeruginosa was observed compared to NO-releasing particles alone. PMID:22998760

  5. Synthesis, characterization, and controlled release of selenium nanoparticles stabilized by chitosan of different molecular weights.

    PubMed

    Zhang, Chunyue; Zhai, Xiaona; Zhao, Guanghua; Ren, Fazheng; Leng, Xiaojing

    2015-12-10

    Chitosan-stabilized selenium nanoparticles (SeNPs) have been reported, but there is no information on the effect of the chitosan molecular weight on the structure, stability, and selenium release properties of the SeNPs. Herein, we compared the uniform Se(0) spherical nanoparticles prepared through the reduction of seleninic acid with ascorbic acid in the presence of chitosan with different molecular weights (Mws). We found that both low and high molecular weight chitosan-stabilized selenium nanoparticles exhibited core-shell microstructures with a size of about 103 nm after 30 days growing through the "bottom-up approach" and "top-down approach," respectively. Moreover, both chitosan SeNPs processed excellent stability towards pH and enzyme treatment. In contrast, selenium was easily released to different extents from these two chitosan SeNPs upon treatment with different free radicals. This makes these materials potentially useful as oral antioxidant supplements. PMID:26428112

  6. Controlled release study of an anti-carcinogenic agent, gallate from the surface of magnetite nanoparticles

    NASA Astrophysics Data System (ADS)

    Ghotbi, Mohammad Yeganeh; bin Hussein, Mohd Zobir

    2012-07-01

    Immobilization of gallate anion, an anti-carcinogenic, anti-mutagenic, and anti-microbial agent on the surface of magnetite nanoparticles was accomplished by adsorption technique for the formation of a core-shell nanocomposite. A simple co-precipitation technique in the presence of poly vinyl pyrrolidone was successfully applied for the preparation of magnetite nanoparticles as core beads with narrow size distribution. The powders were characterized by X-ray diffraction, particle size analysis, magnetic measurements, atomic force microscope and also infrared spectroscopy. FTIR and CHNS results indicated that the gallate anion was actually adsorbed onto the surface of the magnetite nanoparticles. The release of the anion from the surface of the nanocomposite was found to be controllable by the selection of the release media.

  7. Synthesis, characterization, and controlled release of selenium nanoparticles stabilized by chitosan of different molecular weights.

    PubMed

    Zhang, Chunyue; Zhai, Xiaona; Zhao, Guanghua; Ren, Fazheng; Leng, Xiaojing

    2015-12-10

    Chitosan-stabilized selenium nanoparticles (SeNPs) have been reported, but there is no information on the effect of the chitosan molecular weight on the structure, stability, and selenium release properties of the SeNPs. Herein, we compared the uniform Se(0) spherical nanoparticles prepared through the reduction of seleninic acid with ascorbic acid in the presence of chitosan with different molecular weights (Mws). We found that both low and high molecular weight chitosan-stabilized selenium nanoparticles exhibited core-shell microstructures with a size of about 103 nm after 30 days growing through the "bottom-up approach" and "top-down approach," respectively. Moreover, both chitosan SeNPs processed excellent stability towards pH and enzyme treatment. In contrast, selenium was easily released to different extents from these two chitosan SeNPs upon treatment with different free radicals. This makes these materials potentially useful as oral antioxidant supplements.

  8. Cellulose conjugated FITC-labelled mesoporous silica nanoparticles: intracellular accumulation and stimuli responsive doxorubicin release.

    PubMed

    Hakeem, Abdul; Zahid, Fouzia; Duan, Ruixue; Asif, Muhammad; Zhang, Tianchi; Zhang, Zhenyu; Cheng, Yong; Lou, Xiaoding; Xia, Fan

    2016-03-01

    Herein, we design novel cellulose conjugated mesoporous silica nanoparticle (CLS-MSP) based nanotherapeutics for stimuli responsive intracellular doxorubicin (DOX) delivery. DOX molecules are entrapped in pores of the fabricated mesoporous silica nanoparticles (MSPs) while cellulose is used as an encapsulating material through esterification on the outlet of the pores of the MSPs to avoid premature DOX release under physiological conditions. In in vitro studies, stimuli responsive DOX release is successfully achieved from DOX loaded cellulose conjugated mesoporous silica nanoparticles (DOX/CLS-MSPs) by pH and cellulase triggers. Intracellular accumulation of DOX/CLS-MSPs in human liver cancer cells (HepG2 cells) is investigated through confocal microscope magnification. Cell viability of HepG2 cells is determined as the percentage of the cells incubated with DOX/CLS-MSPs compared with that of non-incubated cells through an MTT assay.

  9. Liposome supported metal oxide nanoparticles: interaction mechanism, light controlled content release, and intracellular delivery.

    PubMed

    Wang, Feng; Liu, Juewen

    2014-10-15

    Zwitterionic phosphotydylcholine lipo-somes stably adsorb a number of metal oxide nanoparticles via its phosphate group. This is different from physisorption and fusion with SiO2. The hybrid materials can be internalized by cancer cells and TiO2 allows light controlled liposome content release.

  10. Nanoparticles of lanthanide oxysulfate/oxysulfide for improved oxygen storage/release.

    PubMed

    Zhang, Wuyuan; Arends, Isabel W C E; Djanashvili, Kristina

    2016-09-28

    Lanthanide oxysulfates have the ability to store and release large volumes of oxygen under oxidizing/reducing conditions, rendering them interesting as automotive catalysts. Herein we demonstrate a remarkable improvement of both processes by utilization of nanoparticles compared to the bulk materials. A further improvement of the catalytic activity was achieved by cost-effective doping with 1.9 wt% of Ni.

  11. Preparation and characterization of ketoprofen loaded eudragit RS polymeric nanoparticles for controlled release

    NASA Astrophysics Data System (ADS)

    Anh, Nguyen Tuan; Chi, Nguyen T.; Khai Tran, T.; Tuyen Dao, T. P.; Nhan Le, N. T.; Mau Chien, Dang; Hoai, Nguyen To

    2012-12-01

    Nanospheres containing ketoprofen (Keto) and polymer eudragit RS were prepared using an emulsion solvent evaporation method. The ultrasonic probe (VCX500, vibracell) was used as a tool to disperse oil phase into aqueous phase leading to water/oil emulsion. Nanoparticles were successfully prepared and their morphologies and diameters were confirmed by transmission electron microscope (TEM) and dynamic light scattering (DLS), respectively. The result showed that particles were spherical with submicron size. The particle size was dependent on the RS concentration, emulsification tools and the types of organic solvents. For the encapsulation ability, Keto-loaded RS nanoparticle showed 9.8% of Keto in nanoparticle, which was evaluated by high-performance liquid chromatography (HPLC). Moreover, the drug release behavior of Keto-loaded eudragit RS nanoparticle was also investigated in vitro at pH 7.4 and compared to referential profenid.

  12. Development of a novel antimicrobial-releasing glass ionomer cement functionalized with chlorhexidine hexametaphosphate nanoparticles

    PubMed Central

    2014-01-01

    Background Glass ionomer cements (GICs) are a class of dental biomaterials. They have a wide range of uses including permanent restorations (fillings), cavity linings, fissure sealants and adhesives. One of the most common reasons for replacing a dental restoration is recurrent bacterial tooth decay around the margins of the biomaterial. Therefore, a dental biomaterial which creates a sustained antimicrobial environment around the restoration would be of considerable clinical benefit. In this manuscript, the formulation of a GIC containing novel antimicrobial nanoparticles composed of chlorhexidine hexametaphosphate at 1, 2, 5, 10 and 20% powder substitution by mass is reported. The aim is to create GICs which contain chlorhexidine-hexametaphosphate nanoparticles and characterize the nanoparticle size, morphology and charge and the release of chlorhexidine and fluoride, tensile strength and morphology of the GICs. Results The GICs released chlorhexidine, which is a broad spectrum antimicrobial agent effective against a wide range of oral bacteria, over the duration of the experiment in a dose-dependent manner. This was not at the expense of other properties; fluoride release was not significantly affected by the substitution of antimicrobial nanoparticles in most formulations and internal structure appeared unaffected up to and including 10% substitution. Diametral tensile strength decreased numerically with substitutions of 10 and 20% nanoparticles but this difference was not statistically significant. Conclusion A series of GICs functionalized with chlorhexidine-hexametaphosphate nanoparticles were created for the first time. These released chlorhexidine in a dose-dependent manner. These materials may find application in the development of a new generation of antimicrobial dental nanomaterials. PMID:24456793

  13. Cellulose conjugated FITC-labelled mesoporous silica nanoparticles: intracellular accumulation and stimuli responsive doxorubicin release

    NASA Astrophysics Data System (ADS)

    Hakeem, Abdul; Zahid, Fouzia; Duan, Ruixue; Asif, Muhammad; Zhang, Tianchi; Zhang, Zhenyu; Cheng, Yong; Lou, Xiaoding; Xia, Fan

    2016-02-01

    Herein, we design novel cellulose conjugated mesoporous silica nanoparticle (CLS-MSP) based nanotherapeutics for stimuli responsive intracellular doxorubicin (DOX) delivery. DOX molecules are entrapped in pores of the fabricated mesoporous silica nanoparticles (MSPs) while cellulose is used as an encapsulating material through esterification on the outlet of the pores of the MSPs to avoid premature DOX release under physiological conditions. In in vitro studies, stimuli responsive DOX release is successfully achieved from DOX loaded cellulose conjugated mesoporous silica nanoparticles (DOX/CLS-MSPs) by pH and cellulase triggers. Intracellular accumulation of DOX/CLS-MSPs in human liver cancer cells (HepG2 cells) is investigated through confocal microscope magnification. Cell viability of HepG2 cells is determined as the percentage of the cells incubated with DOX/CLS-MSPs compared with that of non-incubated cells through an MTT assay.Herein, we design novel cellulose conjugated mesoporous silica nanoparticle (CLS-MSP) based nanotherapeutics for stimuli responsive intracellular doxorubicin (DOX) delivery. DOX molecules are entrapped in pores of the fabricated mesoporous silica nanoparticles (MSPs) while cellulose is used as an encapsulating material through esterification on the outlet of the pores of the MSPs to avoid premature DOX release under physiological conditions. In in vitro studies, stimuli responsive DOX release is successfully achieved from DOX loaded cellulose conjugated mesoporous silica nanoparticles (DOX/CLS-MSPs) by pH and cellulase triggers. Intracellular accumulation of DOX/CLS-MSPs in human liver cancer cells (HepG2 cells) is investigated through confocal microscope magnification. Cell viability of HepG2 cells is determined as the percentage of the cells incubated with DOX/CLS-MSPs compared with that of non-incubated cells through an MTT assay. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr08753h

  14. Biosynthesis and the conjugation of magnetite nanoparticles with luteinizing hormone releasing hormone (LHRH).

    PubMed

    Obayemi, J D; Dozie-Nwachukwu, S; Danyuo, Y; Odusanya, O S; Anuku, N; Malatesta, K; Soboyejo, W O

    2015-01-01

    This paper presents the results of an experimental study of the biosynthesis of magnetite nanoparticles (BMNPs) with particle sizes between 10 nm and 60 nm. The biocompatible magnetic nanoparticles are produced from Magnetospirillum magneticum (M.M.) bacteria that respond to magnetic fields. M.M. bacteria were cultured and used to synthesize magnetite nanoparticles. This was done in an enriched magnetic spirillum growth medium (EMSGM) at different pH levels. The nanoparticle concentrations were characterized with UV-Visible (UV-Vis) spectroscopy, while the particle shapes were elucidated via transmission electron microscopy (TEM). The structure of the particles was studied using X-ray diffraction (XRD), while the hydrodynamic radii, particle size distributions and polydispersity of the nanoparticles were characterized using dynamic light scattering (DLS). Carbodiimide reduction was also used to functionalize the BMNPs with a molecular recognition unit (luteinizing hormone releasing hormone, LHRH) that attaches specifically to receptors that are over-expressed on the surfaces of most breast cancer cell types. The resulting nanoparticles were examined using Fourier Transform Infrared (FTIR) spectroscopy and quantitative image analysis. The implications of the results are then discussed for the potential development of magnetic nanoparticles for the specific targeting and treatment of breast cancer.

  15. Overcoming limitations in nanoparticle drug delivery: triggered, intravascular release to improve drug penetration into tumors.

    PubMed

    Manzoor, Ashley A; Lindner, Lars H; Landon, Chelsea D; Park, Ji-Young; Simnick, Andrew J; Dreher, Matthew R; Das, Shiva; Hanna, Gabi; Park, Won; Chilkoti, Ashutosh; Koning, Gerben A; ten Hagen, Timo L M; Needham, David; Dewhirst, Mark W

    2012-11-01

    Traditionally, the goal of nanoparticle-based chemotherapy has been to decrease normal tissue toxicity by improving drug specificity to tumors. The enhanced permeability and retention effect can permit passive accumulation into tumor interstitium. However, suboptimal delivery is achieved with most nanoparticles because of heterogeneities of vascular permeability, which limits nanoparticle penetration. Furthermore, slow drug release limits bioavailability. We developed a fast drug-releasing liposome triggered by local heat that has already shown substantial antitumor efficacy and is in human trials. Here, we show that thermally sensitive liposomes (Dox-TSL) release doxorubicin inside the tumor vasculature. Real-time confocal imaging of doxorubicin delivery to murine tumors in window chambers and histologic analysis of flank tumors illustrates that intravascular drug release increases free drug in the interstitial space. This increases both the time that tumor cells are exposed to maximum drug levels and the drug penetration distance, compared with free drug or traditional pegylated liposomes. These improvements in drug bioavailability establish a new paradigm in drug delivery: rapidly triggered drug release in the tumor bloodstream.

  16. Double loaded self-decomposable SiO2 nanoparticles for sustained drug release

    NASA Astrophysics Data System (ADS)

    Zhao, Saisai; Zhang, Silu; Ma, Jiang; Fan, Li; Yin, Chun; Lin, Ge; Li, Quan

    2015-10-01

    Sustained drug release for a long duration is a desired feature of modern drugs. Using double-loaded self-decomposable SiO2 nanoparticles, we demonstrated sustained drug release in a controllable manner. The double loading of the drugs was achieved using two different mechanisms--the first one via a co-growth mechanism, and the second one by absorption. A two-phase sustained drug release was firstly revealed in an in vitro system, and then further demonstrated in mice. After a single intravenous injection, the drug was controllably released from the nanoparticles into blood circulation with a Tmax of about 8 h, afterwards a long lasting release pattern was achieved to maintain drug systemic exposure with a plasma elimination half-life of approximately 28 h. We disclosed that the absorbed drug molecules contributed to the initial fast release for quickly reaching the therapeutic level with relatively higher plasma concentrations, while the ``grown-in'' drugs were responsible for maintaining the therapeutic level via the later controlled slow and sustained release. The present nanoparticle carrier drug configuration and the loading/maintenance release mechanisms provide a promising platform that ensures a prolonged therapeutic effect by controlling drug concentrations within the therapeutic window--a sustained drug delivery system with a great impact on improving the management of chronic diseases.Sustained drug release for a long duration is a desired feature of modern drugs. Using double-loaded self-decomposable SiO2 nanoparticles, we demonstrated sustained drug release in a controllable manner. The double loading of the drugs was achieved using two different mechanisms--the first one via a co-growth mechanism, and the second one by absorption. A two-phase sustained drug release was firstly revealed in an in vitro system, and then further demonstrated in mice. After a single intravenous injection, the drug was controllably released from the nanoparticles into blood

  17. Fracturing fluid cleanup by controlled release of enzymes from polyelectrolyte complex nanoparticles

    NASA Astrophysics Data System (ADS)

    Barati Ghahfarokhi, Reza

    Guar-based polymer gels are used in the oil and gas industry to viscosify fluids used in hydraulic fracturing of production wells, in order to reduce leak-off of fluids and pressure, and improve the transport of proppants. After fracturing, the gel and associated filter cake must be degraded to very low viscosities using breakers to recover the hydraulic conductivity of the well. Enzymes are widely used to achieve this but injecting high concentrations of enzyme may result in premature degradation, or failure to gel; denaturation of enzymes at alkaline pH and high temperature conditions can also limit their applicability. In this study, application of polyelectrolyte nanoparticles for entrapping, carrying, releasing and protecting enzymes for fracturing fluids was examined. The objective of this research is to develop nano-sized carriers capable of carrying the enzymes to the filter cake, delaying the release of enzyme and protecting the enzyme against pH and temperature conditions inhospitable to native enzyme. Polyethylenimine-dextran sulfate (PEI-DS) polyelectrolyte complexes (PECs) were used to entrap two enzymes commonly used in the oil industry in order to obtain delayed release and to protect the enzyme from conditions inhospitable to native enzyme. Stability and reproducibility of PEC nanoparticles was assured over time. An activity measurement method was used to measure the entrapment efficiency of enzyme using PEC nanoparticles. This method was confirmed using a concentration measurement method (SDS-PAGE). Entrapment efficiencies of pectinase and a commercial high-temperature enzyme mixture in polyelectrolyte complex nanoparticles were maximized. Degradation, as revealed by reduction in viscoelastic moduli of borate-crosslinked hydroxypropyl guar (HPG) gel by commercial enzyme loaded in polyelectrolyte nanoparticles, was delayed, compared to equivalent systems where the enzyme mixture was not entrapped. This indicates that PEC nanoparticles delay the

  18. Preparation of photoreactive phospholipid polymer nanoparticles to immobilize and release protein by photoirradiation.

    PubMed

    Chen, Weixin; Inoue, Yuuki; Ishihara, Kazuhiko

    2015-11-01

    Photoreactive and cytocompatible polymer nanoparticles for immobilizing and releasing proteins were prepared. A water-soluble and amphiphilic phospholipid polymer, poly(2-methacryloyloxyethyl phosphorylcholine (MPC)-co-n-butyl methacrylate (BMA)-co-4-(4-(1-methacryloyloxyethyl)-2-methoxy-5-nitrophenoxy) butyric acid (PL)) (PMB-PL) was synthesized. The PMB-PL underwent a cleavage reaction at the PL unit with photoirradiation at a wavelength of 365 nm. Additionally, the PMB-PL took polymer aggregate in aqueous medium and was used to modify the surface of biodegradable poly(L-lactic acid) (PLA) nanoparticle as an emulsifier. The morphology of the PMB-PL/PLA nanoparticle was spherical and approximately 130 nm in diameter. The carboxylic acid group in the PL unit could immobilize proteins by covalent bonding. The bound proteins were released by a photoinduced cleavage reaction. Within 60s, up to 90% of the immobilized proteins was released by photoirradiation. From these results and with an understanding of the fundamental properties of MPC polymers, we concluded that PMB-PL/PLA nanoparticles have the potential to be used as smart carriers to deliver proteins to biological systems, such as the inside of living cells.

  19. Synthesis, characterization, release kinetics and toxicity profile of drug-loaded starch nanoparticles.

    PubMed

    El-Naggar, Mehrez E; El-Rafie, M H; El-sheikh, M A; El-Feky, Gina S; Hebeish, A

    2015-11-01

    The current research work focuses on the medical application of the cost-effective cross-linked starch nanoparticles, for the transdermal delivery using Diclofenac sodium (DS) as a model drug. The prepared DS-cross-linked starch nanoparticles were synthesized using nanoprecipitation technique at different concentrations of sodium tripolyphosphate (STPP) in the presence of Tween 80 as a surfactant. The resultant cross-linked starch nanoparticles loaded with DS were characterized using world-class facilities such as TEM, DLS, FT-IR, XRD, and DSc. The efficiency of DS loading was also evaluated via entrapment efficiency as well as in vitro release and histopathological study on rat skin. The optimum nanoparticles formulation selected by the JMP(®) software was the formula that composed of 5% maize starch, 57.7mg DS and 0.5% STPP and 0.4% Tween 80, with particle diameter of about 21.04nm, polydispersity index of 0.2 and zeta potential of -35.3mV. It is also worth noting that this selected formula shows an average entrapment efficiency of 95.01 and sustained DS release up to 6h. The histophathological studies using the best formula on rat skin advocate the use of designed transdermal DS loaded cross-linked starch nanoparticles as it is safe and non-irritant to rat skin. The overall results indicate that, the starch nanoparticles could be considered as a good carrier for DS drug regarding the enhancement in its controlled release and successful permeation, thus, offering a promising nanoparticulate system for the transdermal delivery non-steroidal anti-inflammatory drug (NSAID).

  20. Assessment of nanoparticle release and associated health effect of polymer-silicon composites

    NASA Astrophysics Data System (ADS)

    Zhu, H.; Irfan, A.; Sachse, S.; Njuguna, J.

    2012-09-01

    Little information is currently available on possible release of nanomaterials or/and nanoparticles (NP) from conventional and novel products and associated health effect. This study aimed to assess the possible release of NP during the application stage of conventional and nanoproducts. NP release was monitored during physical processing of polymer-silicon composites, and the toxicity of both the released NP and the raw silica nanomaterials that were used as fillers in the nanocomposites was assessed in vitro using human lung epithelial A549 cells. This study suggests that 1) NP can be released from the conventional and novel polymer-silicon composites under certain application scenario; 2) the level of NP release from polymer composites could be altered by different reinforcement materials; e.g. nanostructured MMT could reduce the release while SiO2 NP could increase the release; 3) working with polymer composites under certain conditions could risk inhalation of high level of polymer NP; 4) raw nanomaterials appeared to be toxic in the chosen in vitro system. Further study of the effect of novel filler materials on NP release from final polymer products and the effect of released NP on environment and human health will inform design of safe materials and minimization of negative impact on the environment and human health.

  1. Comparative study on the uptake and bioimpact of metal nanoparticles released into environment

    NASA Astrophysics Data System (ADS)

    Andries, Maria; Pricop, Daniela; Grigoras, Marian; Lupu, Nicoleta; Sacarescu, Liviu; Creanga, Dorina; Iacomi, Felicia

    2015-12-01

    Metallic particles of very small size are ubiquitously released in the air, water and soil from various natural and artificial sources - the last ones with enhanced extent since nanotechnology development accelerated exponentially. In this study we focused on the impact of metal nanoparticles in vegetal species of agroindustrial interest namely the maize (Zea mais L.). Laboratory simulation of environmental pollution was carried out by using engineered nanoparticles of two types: iron oxides with magnetic properties and gold nanoparticles supplied in the form of dilutes stable suspensions in the culture medium of maize seedlings. Magnetic nanoparticle (MNPs) preparation was performed by applying chemical route from iron ferric and ferrous precursor salts in alkali reaction medium at relatively high temperature (over 80 °C). Gold nanoparticles (GNPs) synthesis was accomplished from auric hydrochloride acid in alkali reaction medium in similar temperature conditions. In both types of metallic nanoparticles citrate ions were used as coating shell with role of suspension stabilization. Plantlet response was assessed at the level of assimilatory pigment contents in green tissue of seedlings in early ontogenetic stages.

  2. Magnetically triggered release of molecular cargo from iron oxide nanoparticle loaded microcapsules

    NASA Astrophysics Data System (ADS)

    Carregal-Romero, Susana; Guardia, Pablo; Yu, Xiang; Hartmann, Raimo; Pellegrino, Teresa; Parak, Wolfgang J.

    2014-12-01

    Photothermal release of cargo molecules has been extensively studied for bioapplications. For instance, microcapsules decorated with plasmonic nanoparticles have been widely used in in vitro assays. However, some concerns about their suitability for some in vivo applications cannot be easily overcome, in particular the limited penetration depth of light (even infrared). Magnetic nanoparticles are alternative heat-mediators for local heating, which can be triggered by applying an alternating magnetic field (AMF). AMFs are much less absorbed by tissue than light and thus can penetrate deeper overcoming the above mentioned limitations. Here we present iron oxide nanocube-modified microcapsules as a platform for magnetically triggered molecular release. Layer-by-layer assembled polyelectrolyte microcapsules with 4.6 μm diameter, which had 18 nm diameter iron oxide nanocubes integrated in their walls, were synthesized. The microcapsules were further loaded with an organic fluorescent polymer (Cascade Blue-labelled dextran), which was used as a model of molecular cargo. Through an AMF the magnetic nanoparticles were able to heat their surroundings and destroy the microcapsule walls, leading to a final release of the embedded cargo to the surrounding solution. The cargo release was monitored in solution by measuring the increase in both absorbance and fluorescence signal after the exposure to an AMF. Our results demonstrate that magnetothermal release of the encapsulated material is possible using magnetic nanoparticles with a high heating performance.Photothermal release of cargo molecules has been extensively studied for bioapplications. For instance, microcapsules decorated with plasmonic nanoparticles have been widely used in in vitro assays. However, some concerns about their suitability for some in vivo applications cannot be easily overcome, in particular the limited penetration depth of light (even infrared). Magnetic nanoparticles are alternative heat

  3. Polypyrrole nanoparticles for tunable, pH-sensitive and sustained drug release

    NASA Astrophysics Data System (ADS)

    Samanta, Devleena; Meiser, Jana L.; Zare, Richard N.

    2015-05-01

    We report the development of a generalized pH-sensitive drug delivery system that can release any charged drug preferentially at the pH range of interest. Our system is based on polypyrrole nanoparticles (PPy NPs), synthesized via a simple one-step microemulsion technique. These nanoparticles are highly monodisperse, stable in solution over the period of a month, and have good drug loading capacity (~15 wt%). We show that PPy NPs can be tuned to release drugs at both acidic and basic pH by varying the pH, the charge of the drug, as well as by adding small amounts of charged amphiphiles. Moreover, these NPs may be delivered locally by immobilizing them in a hydrogel. Our studies show encapsulation within a calcium alginate hydrogel results in sustained release of the incorporated drug for more than 21 days. Such a nanoparticle-hydrogel composite drug delivery system is promising for treatment of long-lasting conditions such as cancer and chronic pain which require controlled, localized, and sustained drug release.

  4. Release of silver and copper nanoparticles from polyethylene nanocomposites and their penetration into Listeria monocytogenes.

    PubMed

    Tamayo, L A; Zapata, P A; Vejar, N D; Azócar, M I; Gulppi, M A; Zhou, X; Thompson, G E; Rabagliati, F M; Páez, M A

    2014-07-01

    Since infection is a major cause of death in a patient whose immune responses have been compromised (immunocompromised patient), considerable attention has been focused on developing materials for the prevention of infections. This has been directed primarily at suppressing or eliminating the host's endogenous microbial burden and decreasing the acquisition of new organisms. In this study, the antibacterial properties of two nanocomposites, polyethylene modified with silver nanoparticles (PE-AgNps) or copper nanoparticles (PE-CuNps), against Listeria monocytogenes have been investigated. In order to elucidate the antibacterial mechanism, specifically whether this mechanism corresponds to bactericidal or bacteriolytic activities, we have determined the extent of release of metal ions (Ag(+) and Cu(2+)) and, also, the morphology of the bacteria. The metal ion release from nanocomposites was followed by inductively coupled plasma spectrometry and the morphology of the bacteria was revealed through examination of ultramicrotomed sections of bacteria in a transmission electron microscope. The study of metal ion release from the nanocomposites shows that for both nanocomposites the amount of ions released varies with time, which initially displays a linear behavior until an asymptotic behavior is reached. Further, TEM images show that silver nanoparticles (AgNps) and copper nanoparticles (CuNps), which are released from the nanocomposites, can penetrate to the cell wall and the plasma membrane of bacteria. Resulting morphological changes involve separation of the cytoplasmic membrane from the cell wall, which is known to be an effect of plasmolysis. It was revealed that the antibacterial abilities of the two nanocomposites against L. monocytogenes are associated with both bactericidal and bacteriolytic effects. PMID:24857461

  5. Sustained release of estrogens from PEGylated nanoparticles for treatment of secondary spinal cord injury

    NASA Astrophysics Data System (ADS)

    Barry, John

    Spinal Cord Injury (SCI) is a debilitating condition which causes neurological damage and can result in paralysis. SCI results in immediate mechanical damage to the spinal cord, but secondary injuries due to inflammation, oxidative damage, and activated biochemical pathways leading to apoptosis exacerbate the injury. The only currently available treatment, methylprednisolone, is controversial because there is no convincing data to support its therapeutic efficacy for SCI treatment. In the absence of an effective SCI treatment option, 17beta-estradiol has gained significant attention for its anti-oxidant, anti-inflammatory, and anti-apoptotic abilities, all events associated with secondary. Sadly, 17beta-estradiol is associated with systemic adverse effects preclude the use of free estrogen even for local administration due to short drug half-life in the body. Biodegradable nanoparticles can be used to increase half-life after local administration and to bestow sustained release. Sustained release using PEGylated biodegradable polymeric nanoparticles constructed from poly(lactic-co-glycolic acid) (PLGA) will endow a consistent, low, but effective dose to be delivered locally. This will limit systemic effects due to local administration and low dose, sustained release. PLGA was chosen because it has been used extensively for sustained release, and has a record of safety in humans. Here, we show the in vitro efficacy of PEGylated nanoparticles loaded with 17beta-estradiol for treatment of secondary SCI. We achieved a high loading efficiency and controlled release from the particles over a several day therapeutic window. The particles also show neuroprotection in two in vitro cell culture models. Both the dose and pretreatment time with nanoparticles was evaluated in an effort to translate the treatment into an animal model for further study.

  6. Synthesis of hybrid inorganic/organic nitric oxide-releasing silica nanoparticles for biomedical applications

    NASA Astrophysics Data System (ADS)

    Carpenter, Alexis Wells

    Nitric oxide (NO) is an endogenously produced free radical involved in a number of physiological processes. Thus, much research has focused on developing scaffolds that store and deliver exogenous NO. Herein, the synthesis of N-diazeniumdiolate-modified silica nanoparticles of various physical and chemical properties for biomedical applications is presented. To further develop NO-releasing silica particles for antimicrobial applications, a reverse microemulsion synthesis was designed to achieve nanoparticles of distinct sizes and similar NO release characteristics. Decreasing scaffold size resulted in improved bactericidal activity against Pseudomonas aeruginosa. Confocal microscopy revealed that the improved efficacy resulted from faster particle-bacterium association kinetics. To broaden the therapeutic potential of NO-releasing silica particles, strategies to tune NO release characteristics were evaluated. Initially, surface hydrophobicity and NO release kinetics were tuned by grafting hydrocarbon- and fluorocarbon-based silanes onto the surface of N-diazeniumdiolate-modified particles. The addition of fluorocarbons resulted in a 10x increase in the NO release half-life. The addition of short-chained hydrocarbons to the particle surface increased their stability in hydrophobic electrospun polyurethanes. Although NO release kinetics were longer than that of unmodified particles, durations were still limited to <7 days. An alternative strategy for increasing NO release duration involved directly stabilizing the N-diazeniumdiolate using O2-protecting groups. O2-Methoxymethyl 1-(4-(3-(trimethoxysilyl)propyl))piperazin-1-yl)diazen-1-ium-1,2-diolate (MOM-Pip/NO) was grafted onto mesoporous silica nanoparticles to yield scaffolds with an NO payload of 2.5 μmol NO/mg and an NO release half-life of 23 d. Doping the MOM-Pip/NO-modified particles into resin composites yielded antibacterial NO-releasing dental restorative materials. A 3-log reduction in viable adhered

  7. Nitric oxide releasing iron oxide magnetic nanoparticles for biomedical applications: cell viability, apoptosis and cell death evaluations

    NASA Astrophysics Data System (ADS)

    de Lima, R.; de Oliveira, J. L.; Ludescher, A.; Molina, M. M.; Itri, R.; Seabra, A. B.; Haddad, P. S.

    2013-04-01

    Nitric oxide (NO) is involved in several physiological and pathophysiological processes, such as control of vascular tone and immune responses against microbes. Thus, there is great interest in the development of NO-releasing materials to carry and deliver NO for biomedical applications. Magnetic iron oxide nanoparticles have been used in important pharmacological applications, including drug-delivery. In this work, magnetic iron oxide nanoparticles were coated with thiol-containing hydrophilic ligands: mercaptosuccinic acid (MSA) and dimercaptosuccinic acid (DMSA). Free thiol groups on the surface of MSA- or DMSA- coated nanoparticles were nitrosated, leading to the formation of NO-releasing iron oxide nanoparticles. The cytotoxicity of MSA- or DMSA-coated magnetic nanoparticles (MNP) (thiolated nanoparticles) and nitrosated MSA- or nitrosated DMSA- coated MNPs (NO-releasing nanoparticles) were evaluated towards human lymphocytes. The results showed that MNP-MSA and MNP-DMSA have low cytotoxicity effects. On the other hand, NO-releasing MNPs were found to increase apoptosis and cell death compared to free NO-nanoparticles. Therefore, the cytotoxicity effects observed for NO-releasing MNPs may result in important biomedical applications, such as the treatment of tumors cells.

  8. Process-generated nanoparticles from ceramic tile sintering: Emissions, exposure and environmental release.

    PubMed

    Fonseca, A S; Maragkidou, A; Viana, M; Querol, X; Hämeri, K; de Francisco, I; Estepa, C; Borrell, C; Lennikov, V; de la Fuente, G F

    2016-09-15

    The ceramic industry is an industrial sector in need of significant process changes, which may benefit from innovative technologies such as laser sintering of ceramic tiles. Such innovations result in a considerable research gap within exposure assessment studies for process-generated ultrafine and nanoparticles. This study addresses this issue aiming to characterise particle formation, release mechanisms and their impact on personal exposure during a tile sintering activity in an industrial-scale pilot plant, as a follow-up of a previous study in a laboratory-scale plant. In addition, possible particle transformations in the exhaust system, the potential for particle release to the outdoor environment, and the effectiveness of the filtration system were also assessed. For this purpose, a tiered measurement strategy was conducted. The main findings evidence that nanoparticle emission patterns were strongly linked to temperature and tile chemical composition, and mainly independent of the laser treatment. Also, new particle formation (from gaseous precursors) events were detected, with nanoparticles <30nm in diameter being formed during the thermal treatment. In addition, ultrafine and nano-sized airborne particles were generated and emitted into workplace air during sintering process on a statistically significant level. These results evidence the risk of occupational exposure to ultrafine and nanoparticles during tile sintering activity since workers would be exposed to concentrations above the nano reference value (NRV; 4×10(4)cm(-3)), with 8-hour time weighted average concentrations in the range of 1.4×10(5)cm(-3) and 5.3×10(5)cm(-3). A potential risk for nanoparticle and ultrafine particle release to the environment was also identified, despite the fact that the efficiency of the filtration system was successfully tested and evidenced a >87% efficiency in particle number concentrations removal.

  9. Dual Stimuli-Responsive Poly(β-amino ester) Nanoparticles for On-Demand Burst Release.

    PubMed

    Lee, Jung Seok; Deng, Xiaojian; Han, Patrick; Cheng, Jianjun

    2015-09-01

    We designed poly(β-amino esters) (PBAEs) bearing both UV light- and pH-sensitive groups and used PBAEs to prepare nanoparticles (NPs) that can be utilized for on-demand burst release of guest molecules in response to multiple triggers. Due to the presence of the photo-cleavable group in each repeating unit of PBAE, rapid release of encapsulated model drug could be achieved even with exposures to low intensity UV (10 mW · cm(-2) ). Especially, the burst release was further accelerated by additional UV treatments in the acidic condition showing the combinatory effect of dual stimuli. We believe these PBAE-based NPs can potentially be used to design intelligent controlled release device and nanomedicines.

  10. Plasmon excitation of supported gold nanoparticles can control molecular release from supramolecular systems.

    PubMed

    Marquez, Daniela T; Carrillo, Adela I; Scaiano, Juan C

    2013-08-20

    Hybrid mesoporous silica materials containing gold nanoparticles (AuNPs) have been investigated as potential molecular delivery systems. The photophysical properties of AuNPs, particularly their plasmon band transitions, have been used to control the rate of the release of naproxen from the pores of mesoporous silica matrices. Two different approaches were employed to incorporate AuNPs into the silica network: that is, grafting (using 3-aminopropyltriethoxisilane) and direct absorption. In this research, the anti-inflamatory drug naproxen serves as a test molecule, showing how localized plasmon heating could be used to modify diffusion kinetics within mesoporous materials. Beyond naproxen release, the methodology developed could be employed to release other drugs, sensors, or active molecules, not just in medicine, but in many other fields where nanotechnology is leading to many innovative applications. The hybrid materials developed show a new simple system to efficiently control the release of active cargo from mesoporous silica matrices.

  11. Hollow polymer nanoparticles with S-nitrosothiols as scaffolds for nitric oxide release.

    PubMed

    Liu, Tuanwei; Zhang, Wei; Yang, Xinlin; Li, Chenxi

    2015-12-01

    This work reported the design, preparation and characterization of functional hollow polymer nanoparticles with S-nitrosothiol (SNO) as scaffolds for nitric oxide (NO) release in PBS buffer and bovine serum. The thiolated hollow polymer nanoparticles were prepared by distillation precipitation polymerization of ethyleneglycol dimethacrylate (EGDMA) and 2-hydroxyethyl methacrylate (HEMA) in presence of 3-(methacryloxy)propyltrimethoxysilane (MPS)-modified silica as seeds and the selective removal of silica core in hydrofluoric acid (HF) aqueous solution together with the subsequent surface esterification of hydroxyl groups with acryloyl chloride to introduce high density of vinyl groups and further Michael addition of carbon-carbon double bonds with hydrosulfide (HS(-)) anions. S-Nitrosothiol (SNO) functionalized hollow polymer nanoparticles were prepared via nitrosation of the surface thiol groups with acidified nitrite. The releasing characters of SNO-functionalized hollow polymer nanoparticles as NO scaffolds with capacity of 1.55 μmol/mg were investigated in different media, including PBS buffer exposure to trace copper cations and in real bovine serum. PMID:26275504

  12. Chloroaluminium phthalocyanine polymeric nanoparticles as photosensitisers: photophysical and physicochemical characterisation, release and phototoxicity in vitro.

    PubMed

    de Paula, Carina Silva; Tedesco, Antonio Cláudio; Primo, Fernando Lucas; Vilela, José Mário Carneiro; Andrade, Margareth Spangler; Mosqueira, Vanessa Carla Furtado

    2013-06-14

    Nanoparticles of poly(d,l-lactide-co-glycolide), poly(d,l-lactide) and polyethylene glycol-block-poly(d,l-lactide) were developed to encapsulate chloroaluminium phthalocyanine (AlClPc), a new hydrophobic photosensitiser used in photodynamic therapy (PDT). The mean nanoparticle size varied from 115 to 274 nm, and the encapsulation efficiency ranged from 57% to 96% due to drug precipitation induced by different types of polymer. All nanoparticle formulations presented negative zeta potential values (-37 mV to -59 mV), explaining their colloidal stability. The characteristic photophysical parameters were analysed: the absorption spectrum profile, fluorescence quantum yield and transient absorbance decay, with similar values for free and nanoparticles of AlClPc. The time-resolved spectroscopy measurements for AlClPc triplet excited state lifetimes indicate that encapsulation in nanocapsules increases triplet lifetime, which is advantageous for PDT efficiency. A sustained release profile over 168 h was obtained using external sink method. An in vitro phototoxic effect higher than 80% was observed in human fibroblasts at low laser light doses (3 J/cm(2)) with 10 μM of AlClPc. The AlClPc loaded within polymeric nanocapsules presented suitable physical stability, improved photophysical properties, sustained released profile and suitable activity in vitro to be considered a promising formulation for PDT.

  13. Polymer nanoparticles for controlled release stimulated by visible light and pH.

    PubMed

    Dong, Jie; Zhang, Ruichen; Wu, Hao; Zhan, Xiaowei; Yang, Huai; Zhu, Siquan; Wang, Guojie

    2014-07-01

    Polymer nanoparticles are prepared by self-assembly of visible light and pH sensitive perylene-functionalized copolymers which are synthesized by quaternization between 1-(bromomethyl)perylene and the dimethylaminoethyl units of poly(dimethylaminoethyl methacrylate) (PDMAEMA). The perylene-containing polymethacrylate segments afford the system visible light responsiveness and the unquaternized PDMAEMA segments afford the system pH responsiveness. The self-assembled nanoparticles exhibit a unique dual stimuli response. They can be photocleaved under visible light irradiation, shrunken to smaller nanoparticles at high pH, and swollen at low pH. The structural change endows the nanoparticle with great potential as a sensitive nanocarrier for controlled release of Nile Red and lysozyme under this stimulation. The visible light responsiveness and synergistic effect on the release of loaded molecules with the dual stimulation may obviate the need for harsh conditions such as UV light or extreme pH stimulation, rendering the system more applicable under mild conditions. PMID:24719021

  14. Direct interaction of hydrophilic gold nanoparticles with dexamethasone drug: loading and release study.

    PubMed

    Venditti, Iole; Fontana, Laura; Fratoddi, Ilaria; Battocchio, Chiara; Cametti, Cesare; Sennato, Simona; Mura, Francesco; Sciubba, Fabio; Delfini, Maurizio; Russo, Maria Vittoria

    2014-03-15

    Water-soluble gold nanoparticles functionalized by sodium 3-mercapto-1-propansulfonate (Au-3MPS) were synthesized with different Au/thiol molar ratios for their ability to interact with biomolecules. In particular, a synthetic glucocorticoid steroid, i.e. dexamethasone (DXM) was selected. Herein, the formation of the Au-3MPS/DXM bioconjugate is reported. Au-3MPS nanoparticles show a plasmon resonance at 520 nm, have a spherical morphology and average size of 7-10 nm. The total number of gold atoms was estimated to be about 10600, with a surface component of 8800 atoms and a number of thiol ligands of about 720, roughly one anchored thiol every 10 surface gold atoms. The drug-nanoparticle interaction occurs through the fluorine atom of DXM and Au(I) atoms on the gold nanoparticle surface. The 3MPS ligands closely pack apart each other to leave room for the DXM, that lies at the gold surface in an unusual, almost parallel feature. The loading efficiency of DXM on Au-3MPS was assessed in the range 70-80%, depending on the thiol content. Moreover, our studies confirmed the drug release of about 70% in 5 days. Thanks to their unique properties, i.e. high water solubility, small size and almost monodispersity, Au-3MPS display high potential in biotechnological and biomedical applications, mainly for the loading and release of water insoluble drugs. PMID:24461817

  15. Nanoparticles of lanthanide oxysulfate/oxysulfide for improved oxygen storage/release.

    PubMed

    Zhang, Wuyuan; Arends, Isabel W C E; Djanashvili, Kristina

    2016-09-28

    Lanthanide oxysulfates have the ability to store and release large volumes of oxygen under oxidizing/reducing conditions, rendering them interesting as automotive catalysts. Herein we demonstrate a remarkable improvement of both processes by utilization of nanoparticles compared to the bulk materials. A further improvement of the catalytic activity was achieved by cost-effective doping with 1.9 wt% of Ni. PMID:27515224

  16. Intracellular accumulation of indium ions released from nanoparticles induces oxidative stress, proinflammatory response and DNA damage.

    PubMed

    Tabei, Yosuke; Sonoda, Akinari; Nakajima, Yoshihiro; Biju, Vasudevanpillai; Makita, Yoji; Yoshida, Yasukazu; Horie, Masanori

    2016-02-01

    Due to the widespread use of indium tin oxide (ITO), it is important to investigate its effect on human health. In this study, we evaluated the cellular effects of ITO nanoparticles (NPs), indium chloride (InCl3) and tin chloride (SnCl3) using human lung epithelial A549 cells. Transmission electron microscopy and inductively coupled plasma mass spectrometry were employed to study cellular ITO NP uptake. Interestingly, greater uptake of ITO NPs was observed, as compared with soluble salts. ITO NP species released could be divided into two types: 'indium release ITO' or 'tin release ITO'. We incubated A549 cells with indium release ITO, tin release ITO, InCl3 or SnCl2 and investigated oxidative stress, proinflammatory response, cytotoxicity and DNA damage. We found that intracellular reactive oxygen species were increased in cells incubated with indium release ITO, but not tin release ITO, InCl3 or SnCl2. Messenger RNA and protein levels of the inflammatory marker, interleukin-8, also increased following exposure to indium release ITO. Furthermore, the alkaline comet assay revealed that intracellular accumulation of indium ions induced DNA damage. Our results demonstrate that the accumulation of ionic indium, but not ionic tin, from ITO NPs in the intracellular matrix has extensive cellular effects.

  17. Copper release from copper nanoparticles in the presence of natural organic matter.

    PubMed

    Wang, Long-Fei; Habibul, Nuzahat; He, Dong-Qin; Li, Wen-Wei; Zhang, Xing; Jiang, Hong; Yu, Han-Qing

    2015-01-01

    Copper nanoparticles (CuNPs) are widely used and inevitably released into aqueous environments, causing ecological and health risks. Ubiquitous natural organic matter (NOM) might affect the copper release behaviors from CuNPs and their toxicity. This work aims to elucidate how NOM affects copper release from CuNPs, with a focus on the impacts of NOM properties and the NOM-CuNPs interaction mechanism. The copper release kinetics and different copper fractions induced by representative NOMs were characterized. The presence of NOM led to a more dispersive state of CuNPs clusters. Copper release mainly resulted from complexation reactions between CuNPs and functional groups of NOM. Humic substances were more effective in releasing copper than sodium alginate and bovine serum albumin, due to a higher amount of functional groups and lower molecular weight, which facilitated the contact and complexion reactions. Chlorination treatment of NOM significantly decelerated copper release due to the destruction of functional groups and less attachment of NOM. However, the copper releasing ability of humic acid was not substantially affected by Ca²⁺-induced coagulation. This study provides better understanding about the persistence and transformation of CuNPs in aquatic environments. PMID:25462713

  18. Light-Triggered Release of DNA from Plasmon-Resonant Nanoparticles

    NASA Astrophysics Data System (ADS)

    Huschka, Ryan

    Plasmon-resonant nanoparticle complexes show promising potential for lighttriggered, controllable delivery of deoxyribonucleic acids (DNA) for research and therapeutic purposes. For example, the approach of RNA interference (RNAi) . using antisense DNA or RNA oligonucleotides to silence activity of a specific pathogenic gene transcript and reduce expression of the encoded protein . is very useful in dissecting genetic function and holds promise as a molecular therapeutic. Herein, we investigate the mechanism and probe the in vitro therapeutic potential of DNA light-triggered release from plasmonic nanoparticles. First, we investigate the mechanism of light-triggered release by dehybridizing double-stranded (dsDNA) via laser illumination from two types of nanoparticle substrates: gold (Au) nanoshells and Au nanorods. Both light-triggered and thermally induced releases are distinctly observable from nanoshell-based complexes. Surprisingly, no analogous measurable light-triggered release was observable from nanorod-based complexes below the DNA melting temperature. These results suggest that a nonthermal mechanism may play a role in light-triggered DNA release. Second, we demonstrate the in vitro light-triggered release of molecules noncovalently attached within dsDNA bound to the Au nanoshell surface. DAPI (4',6- diamidino-2-phenylindole), a bright blue fluorescent molecule that binds reversibly to double-stranded DNA, was chosen to visualize this intracellular light-induced release process. Illumination through the cell membrane of the nanoshell-dsDNA-DAPI complexes dehybridizes the DNA and releases the DAPI molecules within living cells. The DAPI molecules diffuse to the nucleus and associate with the cell's endogenous DNA. This work could have future applications towards drug delivery of molecules that associate with dsDNA. Finally, we demonstrate an engineered Au nanoshell (AuNS)-based therapeutic oligonucleotide delivery vehicle, designed to release its cargo on

  19. Photo, pH, and thermo triple-responsive spiropyran-based copolymer nanoparticles for controlled release.

    PubMed

    Chen, Shuo; Jiang, Fengjuan; Cao, Ziquan; Wang, Guojie; Dang, Zhi-Min

    2015-08-14

    A spiropyran-based amphiphilic random copolymer was synthesized and self-assembled into photo-, pH-, and thermo-responsive micellar nanoparticles. The triple-stimuli triggered morphological changes of the nanoparticles were revealed by TEM and DLS. Highly efficient controlled release of encapsulated molecules, coumarin 102, from the nanoparticles under stimulation of UV light, acid and the combined stimuli could be realized. PMID:26160558

  20. Controlled release of drugs in electrosprayed nanoparticles for bone tissue engineering.

    PubMed

    Jayaraman, Praveena; Gandhimathi, Chinnasamy; Venugopal, Jayarama Reddy; Becker, David Laurence; Ramakrishna, Seeram; Srinivasan, Dinesh Kumar

    2015-11-01

    Generating porous topographic substrates, by mimicking the native extracellular matrix (ECM) to promote the regeneration of damaged bone tissues, is a challenging process. Generally, scaffolds developed for bone tissue regeneration support bone cell growth and induce bone-forming cells by natural proteins and growth factors. Limitations are often associated with these approaches such as improper scaffold stability, and insufficient cell adhesion, proliferation, differentiation, and mineralization with less growth factor expression. Therefore, the use of engineered nanoparticles has been rapidly increasing in bone tissue engineering (BTE) applications. The electrospray technique is advantageous over other conventional methods as it generates nanomaterials of particle sizes in the micro/nanoscale range. The size and charge of the particles are controlled by regulating the polymer solution flow rate and electric voltage. The unique properties of nanoparticles such as large surface area-to-volume ratio, small size, and higher reactivity make them promising candidates in the field of biomedical engineering. These nanomaterials are extensively used as therapeutic agents and for drug delivery, mimicking ECM, and restoring and improving the functions of damaged organs. The controlled and sustained release of encapsulated drugs, proteins, vaccines, growth factors, cells, and nucleotides from nanoparticles has been well developed in nanomedicine. This review provides an insight into the preparation of nanoparticles by electrospraying technique and illustrates the use of nanoparticles in drug delivery for promoting bone tissue regeneration. PMID:26415888

  1. High-Density Protein Loading on Hierarchically Porous Layered Double Hydroxide Composites with a Rational Mesostructure.

    PubMed

    Tokudome, Yasuaki; Fukui, Megu; Tarutani, Naoki; Nishimura, Sari; Prevot, Vanessa; Forano, Claude; Poologasundarampillai, Gowsihan; Lee, Peter D; Takahashi, Masahide

    2016-09-01

    Hierarchically porous biocompatible Mg-Al-Cl-type layered double hydroxide (LDH) composites containing aluminum hydroxide (Alhy) have been prepared using a phase-separation process. The sol-gel synthesis allows for the hierarchical pores of the LDH-Alhy composites to be tuned, leading to a high specific solid surface area per unit volume available for high-molecular-weight protein adsorptions. A linear relationship between the effective surface area, SEFF, and loading capacity of a model protein, bovine serum albumin (BSA), is established following successful control of the structure of the LDH-Alhy composite. The threshold of the mean pore diameter, Dpm, above which BSA is effectively adsorbed on the surface of LDH-Alhy composites, is deduced as 20 nm. In particular, LDH-Alhy composite aerogels obtained via supercritical drying exhibit an extremely high capacity for protein loading (996 mg/g) as a result of a large mean mesopore diameter (>30 nm). The protein loading on LDH-Alhy is >14 times that of a reference LDH material (70 mg/g) prepared via a standard procedure. Importantly, BSA molecules pre-adsorbed on porous composites were successfully released on soaking in ionic solutions (HPO4(2-) and Cl(-) aqueous). The superior capability of the biocompatible LDH materials for loading, encapsulation, and releasing large quantities of proteins was clearly demonstrated. PMID:27501777

  2. High-Density Protein Loading on Hierarchically Porous Layered Double Hydroxide Composites with a Rational Mesostructure.

    PubMed

    Tokudome, Yasuaki; Fukui, Megu; Tarutani, Naoki; Nishimura, Sari; Prevot, Vanessa; Forano, Claude; Poologasundarampillai, Gowsihan; Lee, Peter D; Takahashi, Masahide

    2016-09-01

    Hierarchically porous biocompatible Mg-Al-Cl-type layered double hydroxide (LDH) composites containing aluminum hydroxide (Alhy) have been prepared using a phase-separation process. The sol-gel synthesis allows for the hierarchical pores of the LDH-Alhy composites to be tuned, leading to a high specific solid surface area per unit volume available for high-molecular-weight protein adsorptions. A linear relationship between the effective surface area, SEFF, and loading capacity of a model protein, bovine serum albumin (BSA), is established following successful control of the structure of the LDH-Alhy composite. The threshold of the mean pore diameter, Dpm, above which BSA is effectively adsorbed on the surface of LDH-Alhy composites, is deduced as 20 nm. In particular, LDH-Alhy composite aerogels obtained via supercritical drying exhibit an extremely high capacity for protein loading (996 mg/g) as a result of a large mean mesopore diameter (>30 nm). The protein loading on LDH-Alhy is >14 times that of a reference LDH material (70 mg/g) prepared via a standard procedure. Importantly, BSA molecules pre-adsorbed on porous composites were successfully released on soaking in ionic solutions (HPO4(2-) and Cl(-) aqueous). The superior capability of the biocompatible LDH materials for loading, encapsulation, and releasing large quantities of proteins was clearly demonstrated.

  3. Quantification of nanoparticle release from polymer nanocomposite coatings due to environmental stressing.

    PubMed

    Kim, Yeon Seok; Davis, Rick; Uddin, Nasir; Nyden, Marc; Rabb, Savelas A

    2016-01-01

    Certain engineered nanoparticles (ENP) reduce the flammability of components used in soft furnishings (mattresses and upholstered furniture). However, because of the ENP's small size and ability to interact with biological molecules, these fire retardant ENPs may pose a health and environmental risks, if they are released sometime during the life cycle of the soft furnishing. Quantifying the released amount of these ENPs under normal end-use circumstances provides a basis for assessing their potential health and environmental impact. In this article, we report on efforts to identify suitable methodologies for quantifying the release of carbon nanofibers, carbon nanotubes, and sodium montmorillonites from coatings applied to the surfaces of barrier fabric and polyurethane foam. The ENPs released in simulated chewing and mechanical stressing experiments were collected in aqueous solution and quantified using Ultraviolet-Visible and inductively coupled plasma-optical emission spectroscopy. The microstructures of the released ENPs were characterized using scanning electron microscopy. The reported methodology and results provide important milestones to estimate the impact and toxicity of the ENP release during the life cycle of the nanocomposites. To our knowledge, this is the first study of ENP release from the soft furnishing coating, something that can be important application area for fire safety.

  4. Quantification of nanoparticle release from polymer nanocomposite coatings due to environmental stressing.

    PubMed

    Kim, Yeon Seok; Davis, Rick; Uddin, Nasir; Nyden, Marc; Rabb, Savelas A

    2016-01-01

    Certain engineered nanoparticles (ENP) reduce the flammability of components used in soft furnishings (mattresses and upholstered furniture). However, because of the ENP's small size and ability to interact with biological molecules, these fire retardant ENPs may pose a health and environmental risks, if they are released sometime during the life cycle of the soft furnishing. Quantifying the released amount of these ENPs under normal end-use circumstances provides a basis for assessing their potential health and environmental impact. In this article, we report on efforts to identify suitable methodologies for quantifying the release of carbon nanofibers, carbon nanotubes, and sodium montmorillonites from coatings applied to the surfaces of barrier fabric and polyurethane foam. The ENPs released in simulated chewing and mechanical stressing experiments were collected in aqueous solution and quantified using Ultraviolet-Visible and inductively coupled plasma-optical emission spectroscopy. The microstructures of the released ENPs were characterized using scanning electron microscopy. The reported methodology and results provide important milestones to estimate the impact and toxicity of the ENP release during the life cycle of the nanocomposites. To our knowledge, this is the first study of ENP release from the soft furnishing coating, something that can be important application area for fire safety. PMID:26647208

  5. Preparation of polyelectrolyte complex nanoparticles of chitosan and poly(2-acry1amido-2-methylpropanesulfonic acid) for doxorubicin release.

    PubMed

    Zhang, Liping; Wang, Jie; Ni, Caihua; Zhang, Yanan; Shi, Gang

    2016-01-01

    A new kind of polyelectrolyte complex (PEC) based on cationic chitosan (CS) and anionic poly(2-acry1amido-2-methylpropanesulfonic acid) (PAMPS) was prepared using a polymer-monomer pair reaction system. Chitosan was mixed with 2-acry1amido-2-methylpropanesulfonic acid) (AMPS) in an aqueous solution, followed by polymerization of AMPS. The complex was formed by electrostatic interaction of NH3(+) groups of CS and SO3(-) groups of AMPS, leading to a formation of complex nanoparticles of CS-PAMPS. A series of nanoparticles were obtained by changing the weight ratio of CS to AMPS, the structure and properties of nanoparticles were investigated. It was observed that the nanoparticles possessed spherical morphologies with average diameters from 255 nm to 390 nm varied with compositions of the nanoparticles. The nanoparticles were used as drug vehicles for doxorubicin, displaying relative high drug loading rate and encapsulation rate. The vitro release profiles revealed that the drug release could be controlled by adjusting pH of the release media. The nanoparticles demonstrated apparent advantages such as simple preparation process, free of organic solvents, size controllable, good biodegradability and biocompatibility, and they could be potentially used in drug controlled release field.

  6. Characterization of temperature and pH-responsive poly-N-isopropylacrylamide-co-polymer nanoparticles for the release of antimicrobials

    NASA Astrophysics Data System (ADS)

    Hill, Laura E.; Gomes, Carmen L.

    2014-09-01

    Chitosan and alginate are both pH-responsive biopolymers extracted from crustacean exoskeletons and brown algae, respectively. Poly-N-isopropylacrylamide (PNIPAAM) is a hydrogel that becomes hydrophobic at a lower-critical solution temperature. This study sought to combine pH- and temperature-responsive polymers via crosslinking, in order to create a dual-stimuli responsive polymer for hydrophobic antimicrobial compounds delivery, improving their antimicrobial effects. Cinnamon bark extract (CBE) was used as a model for hydrophobic antimicrobial. Two co-polymers were synthesized to create two nanoparticles types: chitosan-co-PNIPAAM and alginate-co-PNIPAAM. Nanoparticles were formed from the resulting co-polymers using a self-assembly top-down process followed by glutaraldehyde or calcium chloride crosslinking. These nanoparticles were then used as controlled delivery vehicles for CBE, whose rapid release could be triggered by specific external stimuli. For the same pH and temperature conditions, the chitosan-co-PNIPAAM nanoparticles were significantly more potent bacterial inhibitors against both pathogens and also exhibited a faster CBE release over time as well as slightly higher entrapment efficiency. The alginate-co-PNIPAAM nanoparticles were significantly smaller and exhibited a slow, gradual release over a long time period. Although both nanoparticles were able to effectively inhibit pathogen growth at lower (P < 0.05) concentration than free CBE, the chitosan-co-PNIPAAM nanoparticles were more effective in delivering a natural antimicrobial with controlled release against foodborne pathogens.

  7. Preparation of polyelectrolyte complex nanoparticles of chitosan and poly(2-acry1amido-2-methylpropanesulfonic acid) for doxorubicin release.

    PubMed

    Zhang, Liping; Wang, Jie; Ni, Caihua; Zhang, Yanan; Shi, Gang

    2016-01-01

    A new kind of polyelectrolyte complex (PEC) based on cationic chitosan (CS) and anionic poly(2-acry1amido-2-methylpropanesulfonic acid) (PAMPS) was prepared using a polymer-monomer pair reaction system. Chitosan was mixed with 2-acry1amido-2-methylpropanesulfonic acid) (AMPS) in an aqueous solution, followed by polymerization of AMPS. The complex was formed by electrostatic interaction of NH3(+) groups of CS and SO3(-) groups of AMPS, leading to a formation of complex nanoparticles of CS-PAMPS. A series of nanoparticles were obtained by changing the weight ratio of CS to AMPS, the structure and properties of nanoparticles were investigated. It was observed that the nanoparticles possessed spherical morphologies with average diameters from 255 nm to 390 nm varied with compositions of the nanoparticles. The nanoparticles were used as drug vehicles for doxorubicin, displaying relative high drug loading rate and encapsulation rate. The vitro release profiles revealed that the drug release could be controlled by adjusting pH of the release media. The nanoparticles demonstrated apparent advantages such as simple preparation process, free of organic solvents, size controllable, good biodegradability and biocompatibility, and they could be potentially used in drug controlled release field. PMID:26478364

  8. Preparation, in vitro release, and pharmacokinetics in rabbits of lyophilized injection of sorafenib solid lipid nanoparticles

    PubMed Central

    Zhang, Hong; Zhang, Fu-Ming; Yan, Shi-Jun

    2012-01-01

    Sorafenib solid lipid nanoparticles (S-SLN) were prepared by emulsion evaporation–solidification at low temperature. Morphology was examined by transmission electron microscope. Particle size and zeta potential were determined by laser granularity equipment. Encapsulation efficiency (EE) was detected by Sephadex gel chromatography and high-performance liquid chromatography (HPLC). The in vitro release profile of S-SLN was studied with dialysis technology. The lyophilized injection of S-SLN was prepared by freeze drying and analyzed by differential scanning calorimetry. The plasma concentration of sorafenib in blood was determined by HPLC. The solid lipid nanoparticles assumed a spherical shape with an even distribution of diameter and particle size 108.23 ± 7.01 nm (n = 3). The polydispersity index, zeta potential, and EE were determined to be 0.25 ± 0.02, −16.37 ± 0.65 mV, and 93.49% ± 1.87%, respectively (n = 3). The in vitro release accorded with the Weibull distribution model. An equal volume of 15% (w/v) mannitol performed better as the protective agent for a lyophilized injection of S-SLN with a new material phase formation. The pharmacokinetic processes of sorafenib solution and lyophilized injection of S-SLN in vivo were in accordance with the two-compartment and one-compartment models, respectively. S-SLN nanoparticles are thus considered a promising drug-delivery system. PMID:22787390

  9. Development of mesoporous silica-based nanoparticles with controlled release capability for cancer therapy.

    PubMed

    Mekaru, Harutaka; Lu, Jie; Tamanoi, Fuyuhiko

    2015-12-01

    Nanoparticles that respond to internal and external stimuli to carry out controlled release of anticancer drugs have been developed. In this review, we focus on the development of mesoporous silica based nanoparticles, as this type of materials provides a relatively stable material that is amenable to various chemical modifications. We first provide an overview of various designs employed to construct MSN-based controlled release systems. These systems respond to internal stimuli such as pH, redox state and the presence of biomolecules as well as to external stimuli such as light and magnetic field. They are at a different stage of development; depending on the system, their operation has been demonstrated in aqueous solution, in cancer cells or in animal models. Efforts to develop MSNs with multi-functionality will be discussed. Safety and biodegradation of MSNs, issues that need to be overcome for clinical development of MSNs, will be discussed. Advances in the synthesis of mechanized theranostic nanoparticles open up the possibility to start envisioning future needs for medical equipment.

  10. Effect of basic fibroblast growth factor released from chitosan-fucoidan nanoparticles on neurite extension.

    PubMed

    Huang, Yi-Cheng; Yang, Ya-Ting

    2016-05-01

    Exogenous growth factors are an integral part of an effective nerve tissue-engineering strategy. Basic fibroblast growth factor (bFGF) has a marked positive effect on angiogenesis and neuronal cell survival. However, bFGF is limited by its short half-life and easy degradation by enzymes. Therefore, in this study novel biodegradable chitosan-fucoidan nanoparticles (CS-F NPs) were designed to carry bFGFs and maintain their activities. The experimental results indicated that chitosan and fucoidan form stable nanoparticles approximately 200 nm in size via electrostatic interactions. Additionally, the effectiveness of nanoparticles is related to their chitosan:fucoidan weight ratio. The CS-F NPs control the release of bFGFs and protect bFGF from deactivation by heat and enzymes. In vitro cell studies demonstrate that CS-F NPs have no cytotoxicity to PC12 cells, as the concentration of NPs is 125 ng/ml. Moreover, the CS-F NPs significantly decrease the amount of bFGF needed for neurite extension. The cumulative release of bFGF from CS-F NPs at 24 h is 0.168 ng/ml, markedly lower than that in solution (4.2 ng/ml). Importantly, CS-F NPs are potential carriers for delivering bFGFs for nerve tissue engineering. Copyright © 2013 John Wiley & Sons, Ltd.

  11. Well-dispersed lithium amidoborane nanoparticles through nanoreactor engineering for improved hydrogen release.

    PubMed

    Xia, Guanglin; Chen, Jie; Sun, Weiwei; Tan, Yingbin; Guo, Zaiping; Liu, Huakun; Yu, Xuebin

    2014-11-01

    Well-distributed lithium amidoborane (LiAB) nanoparticles were successfully fabricated via adopting carbon nanofibers (CNFs) with homogenous pores uniformly containing Li3N as the nanoreactor and reactant, simply prepared by a single-nozzle electrospinning technique, for the subsequent interaction with AB. The hierarchical porous structure consists of various macropores, mesopores and micropores in situ produced during the formation of Li3N simultaneously serving as the reaction initiator, which not only controllably realizes the well-distribution of LiAB nanoparticles but also provides favorable channels for hydrogen release. Because of the hierarchical porous architecture and nanoscale size effects, the LiAB nanoparticles start to release hydrogen at only 40 °C, which is 30 °C lower than that of pure LiAB, and dehydrogenate completely within only 15 min at 100 °C (10.6 wt%). This work provides a new perspective to the controllable fabrication of nanosized hydrogen storage materials.

  12. Light- and pH-activated intracellular drug release from polymeric mesoporous silica nanoparticles.

    PubMed

    Tian, Ye; Kong, Yi; Li, Xiaojian; Wu, Jun; Ko, Alex C-T; Xing, Malcolm

    2015-10-01

    Surface modified mesoporous silica nanoparticles (MSNs) with reduced toxicity were prepared for light and pH dual triggerable drug delivery system. Both 413 nm light and acidic environment can activate the drug release process, improving the pharmacological action. By applying rhodamine B (RhB) as a model drug, the accumulative RhB release is as high as 95% in pH 5.0 and in irradiation of 413 nm light, compared to only 55% in pH 7.4 and in dark. The anti-cancer drug camptothecin (CPT) loaded nanoparticles can kill cancer cells with IC₅₀ value of 0.02 μg mL(-1) in exposure of 413 nm light, which is much lower than free CPT (about 0.1 μg mL(-1)). Multimodal nonlinear optical imaging microscopy (NLOM) was employed to acquire in vitro coherent anti-Stokes Raman (CARS) and two-photon excited fluorescence (TPEF) images of live MCF-7 cells and showed that the nanoparticles can be taken up by breast tumor cell MCF-7 with high efficiency, indicating its great potential for anti-cancer drug delivery system. PMID:26188470

  13. Anoxia-induced release of colloid- and nanoparticle-bound phosphorus in grassland soils.

    PubMed

    Henderson, R; Kabengi, N; Mantripragada, N; Cabrera, M; Hassan, S; Thompson, A

    2012-11-01

    Particle-facilitated transport is a key mechanism of phosphorus (P) loss in agroecosystems. We assessed contributions of colloid- and nanoparticle-bound P (nPP; 1-415 nm) to total P released from grassland soils receiving biannual poultry litter applications since 1995. In laboratory incubations, soils were subjected to 7 days of anoxic conditions or equilibrated at pH 6 and 8 under oxic conditions and then the extract was size fractionated by differential centrifugation/ultrafiltration for analysis of P, Al, Fe, Si, Ti, and Ca. Selected samples were characterized by transmission electron microscopy-energy dispersive spectroscopy (TEM-EDS) and field flow fractionation (FFF-ICP-MS). Particles released were present as nanoaggregates with a mean diameter of 200-250 nm, composed of ~50-nm aluminosilicate flakes studded with Fe and Ti-rich clusters (<10 nm) that contained most of the P detected by EDS. Anoxic incubation of stimulated nPP release with seasonally saturated soils released more nPP and Fe(2+)(aq) than well-drained soils; whereas, nonreductive particle dispersion, accomplished by raising the pH, yielded no increase in nPP release. This suggests Fe acts as a cementing agent, binding to the bulk soil P-bearing colloids that can be released during reducing conditions. Furthermore, it suggests prior periodic exposure to anoxic conditions increases susceptibility to redox-induced P mobilization. PMID:23017121

  14. Development of Nanoparticles Incorporating a Novel Liposomal Membrane Destabilization Peptide for Efficient Release of Cargos into Cancer Cells

    PubMed Central

    Ohgita, Takashi; Kogure, Kentaro

    2014-01-01

    In anti-cancer therapy mediated by a nanoparticle-based drug delivery system (DDS), overall efficacy depends on the release efficiency of cargos from the nanoparticles in the cancer cells as well as the specificity of delivery to tumor tissue. However, conventional liposome-based DDS have no mechanism for specifically releasing the encapsulated cargos inside the cancer cells. To overcome this barrier, we developed nanoparticles containing a novel liposomal membrane destabilization peptide (LMDP) that can destabilize membranes by cleavage with intramembranous proteases on/in cancer cells. Calcein encapsulated in liposomes modified with LMDP (LMDP-lipo) was effectively released in the presence of a membrane fraction containing an LMDP-cleavable protease. The release was inhibited by a protease inhibitor, suggesting that LMDP-lipo could effectively release its cargo into cells in response to a cancer-specific protease. Moreover, when LMDP-lipo contained fusogenic lipids, the release of cargo was accelerated, suggesting that the fusion of LMDP-lipo with cellular membranes was the initial step in the intracellular delivery. Time-lapse microscopic observations showed that the release of cargo from LMDP-lipo occurred immediately after association of LMDP-lipo with target cells. Consequently, LMDP-lipo could be a useful nanoparticle capable of effective release of cargos specifically into targeted cancer cells. PMID:25343714

  15. Silicon Impurity Release and Surface Transformation of TiO2 Anatase and Rutile Nanoparticles in Water Environments

    EPA Science Inventory

    Surface transformation can affect the stability, reactivity, and toxicity of titanium dioxide (TiO2) nanoparticles (NPs) when released to water environments. Herein, we investigated the release kinetics of Si impurity frequently introduced during NP synthesis and the resulting ef...

  16. Targeted and controlled anticancer drug delivery and release with magnetoelectric nanoparticles

    NASA Astrophysics Data System (ADS)

    Rodzinski, Alexandra; Guduru, Rakesh; Liang, Ping; Hadjikhani, Ali; Stewart, Tiffanie; Stimphil, Emmanuel; Runowicz, Carolyn; Cote, Richard; Altman, Norman; Datar, Ram; Khizroev, Sakhrat

    2016-02-01

    It is a challenge to eradicate tumor cells while sparing normal cells. We used magnetoelectric nanoparticles (MENs) to control drug delivery and release. The physics is due to electric-field interactions (i) between MENs and a drug and (ii) between drug-loaded MENs and cells. MENs distinguish cancer cells from normal cells through the membrane’s electric properties; cancer cells have a significantly smaller threshold field to induce electroporation. In vitro and in vivo studies (nude mice with SKOV-3 xenografts) showed that (i) drug (paclitaxel (PTX)) could be attached to MENs (30-nm CoFe2O4@BaTiO3 nanostructures) through surface functionalization to avoid its premature release, (ii) drug-loaded MENs could be delivered into cancer cells via application of a d.c. field (~100 Oe), and (iii) the drug could be released off MENs on demand via application of an a.c. field (~50 Oe, 100 Hz). The cell lysate content was measured with scanning probe microscopy and spectrophotometry. MENs and control ferromagnetic and polymer nanoparticles conjugated with HER2-neu antibodies, all loaded with PTX were weekly administrated intravenously. Only the mice treated with PTX-loaded MENs (15/200 μg) in a field for three months were completely cured, as confirmed through infrared imaging and post-euthanasia histology studies via energy-dispersive spectroscopy and immunohistochemistry.

  17. Targeted and controlled anticancer drug delivery and release with magnetoelectric nanoparticles

    PubMed Central

    Rodzinski, Alexandra; Guduru, Rakesh; Liang, Ping; Hadjikhani, Ali; Stewart, Tiffanie; Stimphil, Emmanuel; Runowicz, Carolyn; Cote, Richard; Altman, Norman; Datar, Ram; Khizroev, Sakhrat

    2016-01-01

    It is a challenge to eradicate tumor cells while sparing normal cells. We used magnetoelectric nanoparticles (MENs) to control drug delivery and release. The physics is due to electric-field interactions (i) between MENs and a drug and (ii) between drug-loaded MENs and cells. MENs distinguish cancer cells from normal cells through the membrane’s electric properties; cancer cells have a significantly smaller threshold field to induce electroporation. In vitro and in vivo studies (nude mice with SKOV-3 xenografts) showed that (i) drug (paclitaxel (PTX)) could be attached to MENs (30-nm CoFe2O4@BaTiO3 nanostructures) through surface functionalization to avoid its premature release, (ii) drug-loaded MENs could be delivered into cancer cells via application of a d.c. field (~100 Oe), and (iii) the drug could be released off MENs on demand via application of an a.c. field (~50 Oe, 100 Hz). The cell lysate content was measured with scanning probe microscopy and spectrophotometry. MENs and control ferromagnetic and polymer nanoparticles conjugated with HER2-neu antibodies, all loaded with PTX were weekly administrated intravenously. Only the mice treated with PTX-loaded MENs (15/200 μg) in a field for three months were completely cured, as confirmed through infrared imaging and post-euthanasia histology studies via energy-dispersive spectroscopy and immunohistochemistry. PMID:26875783

  18. Optimization of caseinate-coated simvastatin-zein nanoparticles: improved bioavailability and modified release characteristics

    PubMed Central

    Ahmed, Osama AA; Hosny, Khaled M; Al-Sawahli, Majid M; Fahmy, Usama A

    2015-01-01

    The current study focuses on utilization of the natural biocompatible polymer zein to formulate simvastatin (SMV) nanoparticles coated with caseinate, to improve solubility and hence bioavailability, and in addition, to modify SMV-release characteristics. This formulation can be utilized for oral or possible depot parenteral applications. Fifteen formulations were prepared by liquid–liquid phase separation method, according to the Box–Behnken design, to optimize formulation variables. Sodium caseinate was used as an electrosteric stabilizer. The factors studied were: percentage of SMV in the SMV-zein mixture (X1), ethanol concentration (X2), and caseinate concentration (X3). The selected dependent variables were mean particle size (Y1), SMV encapsulation efficiency (Y2), and cumulative percentage of drug permeated after 1 hour (Y3). The diffusion of SMV from the prepared nanoparticles specified by the design was carried out using an automated Franz diffusion cell apparatus. The optimized SMV-zein formula was investigated for in vivo pharmacokinetic parameters compared with an oral SMV suspension. The optimized nanosized SMV-zein formula showed a 131 nm mean particle size and 89% encapsulation efficiency. In vitro permeation studies displayed delayed permeation characteristics, with about 42% and 85% of SMV cumulative amount released after 12 and 48 hours, respectively. Bioavailability estimation in rats revealed an augmentation in SMV bioavailability from the optimized SMV-zein formulation, by fourfold relative to SMV suspension. Formulation of caseinate-coated SMV-zein nanoparticles improves the pharmacokinetic profile and bioavailability of SMV. Accordingly, improved hypolipidemic activities for longer duration could be achieved. In addition, the reduced dosage rate of SMV-zein nanoparticles improves patient tolerability and compliance. PMID:25670883

  19. Water state effect on drug release from an antibiotic loaded polyurethane matrix containing albumin nanoparticles.

    PubMed

    Martinelli, Andrea; D'Ilario, Lucio; Francolini, Iolanda; Piozzi, Antonella

    2011-04-01

    Water mobility plays a crucial role in determining transport properties of small molecules in polymer matrices. In particular, in drug delivery systems, water state affects the pharmacokinetics, especially drug absorption, diffusion and release. In the present study, the state of water in an antibiotic-loaded composite consisting of albumin nanoparticles (BSA(np)) dispersed into a carboxylated polyurethane (PEUA) has been investigated and compared with that of the single drug-loaded components. The antibiotic cefamandole nafate was used as a model drug. DSC analysis, used to evaluate the freezing and non-freezing water fractions in the hydrated samples, showed that in BSA(np) water can adsorb both in the inter-particles regions and inside the particles. With increasing of total adsorbed water amount, the contribution of the freezing water fraction was higher than the non-freezing one. As for PEUA, the majority of water molecules absorbed is in a mobile freezing state (about 60% of the W(tot)). As for the PEUA/BSA(np) composite, the higher polyurethane phase segregation induced by the nanoparticles as well as the higher non-freezing water fraction significantly enhanced drug uptake with respect to PEUA. Moreover, the greater non-freezing water fraction allowed the drug to penetrate within BSA nanoparticles and to give rise then to a controlled drug release. Indeed, the diffusion barrier exerted by nanoparticles and the matrix prolonged the antimicrobial activity from 4 to 9 days. Finally, the higher polyurethane phase segregation also improved composite mechanical properties, as evidenced in stress-strain experiments and dynamic mechanical analysis.

  20. Temperature-tunable iron oxide nanoparticles for remote-controlled drug release.

    PubMed

    Dani, Raj K; Schumann, Canan; Taratula, Olena; Taratula, Oleh

    2014-08-01

    Herein, we report the successful development of a novel nanosystem capable of an efficient delivery and temperature-triggered drug release specifically aimed at cancer. The water-soluble 130.1 ± 0.2 nm iron oxide nanoparticles (IONPs) were obtained via synthesis of a monodispersed iron oxide core stabilized with tetramethylammonium hydroxide pentahydrate (TMAOH), followed by coating with the thermoresponsive copolymer poly-(NIPAM-stat-AAm)-block-PEI (PNAP). The PNAP layer on the surface of the IONP undergoes reversible temperature-dependent structural changes from a swollen to a collapsed state resulting in the controlled release of anticancer drugs loaded in the delivery vehicle. We demonstrated that the phase transition temperature of the prepared copolymer can be precisely tuned to the desired value in the range of 36°C-44°C by changing the monomers ratio during the preparation of the nanoparticles. Evidence of modification of the IONPs with the thermoresponsive copolymer is proven by ATR-FTIR and a quantitative analysis of the polymeric and iron oxide content obtained by thermogravimetric analysis. When loaded with doxorubicin (DOX), the IONPs-PNAP revealed a triggered drug release at a temperature that is a few degrees higher than the phase transition temperature of a copolymer. Furthermore, an in vitro study demonstrated an efficient internalization of the nanoparticles into the cancer cells and showed that the drug-free IONPs-PNAP were nontoxic toward the cells. In contrast, sufficient therapeutic effect was observed for the DOX-loaded nanosystem as a function of temperature. Thus, the developed temperature-tunable IONPs-based delivery system showed high potential for remotely triggered drug delivery and the eradication of cancer cells. PMID:24821220

  1. Solid lipid nanoparticles as carrier for sunscreens: in vitro release and in vivo skin penetration.

    PubMed

    Wissing, S A; Müller, R H

    2002-06-17

    The aim of this study was the comparison of two different formulations (solid lipid nanoparticles (SLN) and conventional o/w emulsion) as carrier systems for the molecular sunscreen oxybenzone. The influence of the carrier on the rate of release was studied in vitro with a membrane-free model. The release rate could be decreased by up to 50% with the SLN formulation. Further in vitro measurements with static Franz diffusion cells were performed. In vivo, penetration of oxybenzone into stratum corneum on the forearm was investigated by the tape stripping method. It was shown that the rate of release is strongly dependent upon the formulation and could be decreased by 30-60% in SLN formulations. In all test models, oxybenzone was released and penetrated into human skin more quickly and to a greater extent from the emulsions. The rate of release also depends upon the total concentration of oxybenzone in the formulation. In vitro-in vivo correlations could be made qualitatively.

  2. Silver nanoparticles embedded in zeolite membranes: release of silver ions and mechanism of antibacterial action

    PubMed Central

    Nagy, Amber; Harrison, Alistair; Sabbani, Supriya; Munson, Robert S; Dutta, Prabir K; Waldman, W James

    2011-01-01

    Background The focus of this study is on the antibacterial properties of silver nanoparticles embedded within a zeolite membrane (AgNP-ZM). Methods and Results These membranes were effective in killing Escherichia coli and were bacteriostatic against methicillin-resistant Staphylococcus aureus. E. coli suspended in Luria Bertani (LB) broth and isolated from physical contact with the membrane were also killed. Elemental analysis indicated slow release of Ag+ from the AgNP-ZM into the LB broth. The E. coli killing efficiency of AgNP-ZM was found to decrease with repeated use, and this was correlated with decreased release of silver ions with each use of the support. Gene expression microarrays revealed upregulation of several antioxidant genes as well as genes coding for metal transport, metal reduction, and ATPase pumps in response to silver ions released from AgNP-ZM. Gene expression of iron transporters was reduced, and increased expression of ferrochelatase was observed. In addition, upregulation of multiple antibiotic resistance genes was demonstrated. The expression levels of multicopper oxidase, glutaredoxin, and thioredoxin decreased with each support use, reflecting the lower amounts of Ag+ released from the membrane. The antibacterial mechanism of AgNP-ZM is proposed to be related to the exhaustion of antioxidant capacity. Conclusion These results indicate that AgNP-ZM provide a novel matrix for gradual release of Ag+. PMID:21931480

  3. Development of oral sustained release rifampicin loaded chitosan nanoparticles by design of experiment.

    PubMed

    Patel, Bhavin K; Parikh, Rajesh H; Aboti, Pooja S

    2013-01-01

    Objective. The main objective of the present investigation was to develop and optimize oral sustained release Chitosan nanoparticles (CNs) of rifampicin by design of experiment (DOE). Methodology. CNs were prepared by modified emulsion ionic gelation technique. Here, inclusion of hydrophobic drug moiety in the hydrophilic matrix of polymer is applied for rifampicin delivery using CN. The 2(3) full-factorial design was employed by selecting the independent variables such as Chitosan concentration (X 1), concentration of tripolyphosphate (X 2), and homogenization speed (X 3) in order to achieve desired particle size with maximum percent entrapment efficiency and drug loading. The design was validated by checkpoint analysis, and formulation was optimized using the desirability function. Results. Particle size, drug entrapment efficiency, and drug loading for the optimized batch were found to be 221.9 nm, 44.17 ± 1.98% W/W, and 42.96 ± 2.91% W/W, respectively. In vitro release data of optimized formulation showed an initial burst followed by slow sustained drug release. Kinetic drug release from CNs was best fitted to Higuchi model. Conclusion. Design of Experiment is an important tool for obtaining desired characteristics of rifampicin loaded CNs. In vitro study suggests that oral sustained release CNs might be an effective drug delivery system for tuberculosis.

  4. Utilizing the protein corona around silica nanoparticles for dual drug loading and release

    NASA Astrophysics Data System (ADS)

    Shahabi, Shakiba; Treccani, Laura; Dringen, Ralf; Rezwan, Kurosch

    2015-10-01

    A protein corona forms spontaneously around silica nanoparticles (SNPs) in serum-containing media. To test whether this protein corona can be utilized for the loading and release of anticancer drugs we incorporated the hydrophilic doxorubicin, the hydrophobic meloxicam as well as their combination in the corona around SNPs. The application of corona-covered SNPs to osteosarcoma cells revealed that drug-free particles did not affect the cell viability. In contrast, SNPs carrying a protein corona with doxorubicin or meloxicam lowered the cell proliferation in a concentration-dependent manner. In addition, these particles had an even greater antiproliferative potential than the respective concentrations of free drugs. The best antiproliferative effects were observed for SNPs containing both doxorubicin and meloxicam in their corona. Co-localization studies revealed the presence of doxorubicin fluorescence in the nucleus and lysosomes of cells exposed to doxorubicin-containing coated SNPs, suggesting that endocytotic uptake of the SNPs facilitates the cellular accumulation of the drug. Our data demonstrate that the protein corona, which spontaneously forms around nanoparticles, can be efficiently exploited for loading the particles with multiple drugs for therapeutic purposes. As drugs are efficiently released from such particles they may have a great potential for nanomedical applications.A protein corona forms spontaneously around silica nanoparticles (SNPs) in serum-containing media. To test whether this protein corona can be utilized for the loading and release of anticancer drugs we incorporated the hydrophilic doxorubicin, the hydrophobic meloxicam as well as their combination in the corona around SNPs. The application of corona-covered SNPs to osteosarcoma cells revealed that drug-free particles did not affect the cell viability. In contrast, SNPs carrying a protein corona with doxorubicin or meloxicam lowered the cell proliferation in a concentration

  5. A tumor mRNA-dependent gold nanoparticle-molecular beacon carrier for controlled drug release and intracellular imaging.

    PubMed

    Qiao, Guangming; Zhuo, Linhai; Gao, Yuan; Yu, Lijuan; Li, Na; Tang, Bo

    2011-07-14

    We demonstrate a tumor mRNA-dependent drug carrier for controlled release of doxorubicin (Dox) and intracellular imaging based on gold nanoparticle-molecular beacon. Fluorescent Dox is released effectively and induces apoptosis in breast cancer cells but not in normal cells. Significantly, the release of Dox is correlated positively with the quantities of tumor mRNA, which is according to various stages of tumor progression, and so can decrease effectively side effects of Dox.

  6. Development of thermosensitive poly(n-isopropylacrylamide-co-((2-dimethylamino) ethyl methacrylate))-based nanoparticles for controlled drug release

    NASA Astrophysics Data System (ADS)

    Peng, Cheng-Liang; Tsai, Han-Min; Yang, Shu-Jyuan; Luo, Tsai-Yueh; Lin, Chia-Fu; Lin, Wuu-Jyh; Shieh, Ming-Jium

    2011-07-01

    Thermosensitive nanoparticles based on poly(N-isopropylacrylamide-co-((2-dimethylamino)ethylmethacrylate)) (poly(NIPA-co-DMAEMA)) copolymers were successfully fabricated by free radical polymerization. The lower critical solution temperature (LCST) of the synthesized nanoparticles was 41 °C and a temperature above which would cause the nanoparticles to undergo a volume phase transition from 140 to 100 nm, which could result in the expulsion of encapsulated drugs. Therefore, we used the poly(NIPA-co-DMAEMA) nanoparticles as a carrier for the controlled release of a hydrophobic anticancer agent, 7-ethyl-10-hydroxy-camptothecin (SN-38). The encapsulation efficiency and loading content of SN-38-loaded nanoparticles at an SN-38/poly(NIPA-co-DMAEMA) ratio of 1/10 (D/P = 1/10) were about 80% and 6.293%, respectively. Moreover, the release profile of SN-38-loaded nanoparticles revealed that the release rate at 42 °C (above LCST) was higher than that at 37 °C (below LCST), which demonstrated that the release of SN-38 could be controlled by increasing the temperature. The cytotoxicity of the SN-38-loaded poly(NIPA-co-DMAEMA) nanoparticles was investigated in human colon cancer cells (HT-29) to compare with the treatment of an anticancer drug, Irinotecan® (CPT-11). The antitumor efficacy evaluated in a C26 murine colon tumor model showed that the SN-38-loaded nanoparticles in combination with hyperthermia therapy efficiently suppressed tumor growth. The results indicate that these thermo-responsive nanoparticles are potential carriers for controlled drug delivery.

  7. Entrapment of basic fibroblast growth factor (bFGF) in a succinylated chitosan nanoparticle delivery system and release profile.

    PubMed

    Butko, Alison; Bonat Celli, Giovana; Paulson, Allan; Ghanem, Amyl

    2016-07-01

    Basic fibroblast growth factor (bFGF) helps to regulate the proliferation and migration of fibroblasts, the proliferation of endothelial cells, and aids the development of angiogenesis. Its in vivo half-life is on the order of minutes due to extensive degradation and inactivation, which could be potentially reduced by controlled release vehicles. In this study, bFGF was entrapped into chitosan (CS) and N-succinyl-chitosan (SC) nanoparticles, with and without heparin, at two levels of initial loading, followed by further characterization of the particles. Release studies were conducted using radiolabeled bFGF-loaded nanoparticles. Both types of nanoparticles loaded similar amounts of bFGF (60.2 and 68.6% for CS and SC, respectively). The release profile varied greatly among the samples, and a burst release was observed in most cases, with the release amount approaching its final value in the first 6 h. The final amount released varied from 1.5 to 18% of the amount of bFGF-entrapped. The concomitant encapsulation of heparin and the use of SC as a nanoparticle matrix contributed to the largest amount of bFGF release (18%) over the time investigated.

  8. Biocompatible zwitterionic sulfobetaine copolymer-coated mesoporous silica nanoparticles for temperature-responsive drug release.

    PubMed

    Sun, Jiao-Tong; Yu, Zhi-Qiang; Hong, Chun-Yan; Pan, Cai-Yuan

    2012-05-14

    A novel nanocontainer, which could regulate the release of payloads, has been successfully fabricated by attaching zwitterionic sulfobetaine copolymer onto the mesoporous silica nanoparticles (MSNs). RAFT polymerization is employed to prepare the hybrid poly(2-(dimethylamino)ethyl methacrylate)-coated MSNs (MSN-PDMAEMA). Subsequently, the tertiary amine groups in PDMAEMA are quaternized with 1,3-propanesultone to get poly(DMAEMA-co-3-dimethyl(methacryloyloxyethyl)ammonium propanesulfonate)-coated MSNs [MSN-Poly(DMAEMA-co-DMAPS)]. The zwitterionic PDMAPS component endows the nanocarrier with biocompatibility, and the PDMAEMA component makes the copolymer shell temperature-responsive. Controlled release of loaded rhodamine B has been achieved in the saline solutions. PMID:22488562

  9. Influence of Parathyroid Hormone-Loaded PLGA Nanoparticles in Porous Scaffolds for Bone Regeneration

    PubMed Central

    Gentile, Piergiorgio; Nandagiri, Vijay Kumar; Pabari, Ritesh; Daly, Jacqueline; Tonda-Turo, Chiara; Ciardelli, Gianluca; Ramtoola, Zebunnissa

    2015-01-01

    Biodegradable poly(lactide-co-glycolide) (PLGA) nanoparticles, containing human parathyroid hormone (PTH (1–34)), prepared by a modified double emulsion-solvent diffusion-evaporation method, were incorporated in porous freeze-dried chitosan-gelatin (CH-G) scaffolds. The PTH-loaded nanoparticles (NPTH) were characterised in terms of morphology, size, protein loading, release kinetics and in vitro assessment of biological activity of released PTH and cytocompatibility studies against clonal human osteoblast (hFOB) cells. Structural integrity of incorporated and released PTH from nanoparticles was found to be intact by using Tris-tricine SDS-PAGE. In vitro PTH release kinetics from PLGA nanoparticles were characterised by a burst release followed by a slow release phase for 3–4 weeks. The released PTH was biologically active as evidenced by the stimulated release of cyclic AMP from hFOB cells as well as increased mineralisation studies. Both in vitro and cell studies demonstrated that the PTH bioactivity was maintained during the fabrication of PLGA nanoparticles and upon release. Finally, a content of 33.3% w/w NPTHs was incorporated in CH-G scaffolds, showing an intermittent release during the first 10 days and, followed by a controlled release over 28 days of observation time. The increased expression of Alkaline Phosphatase levels on hFOB cells further confirmed the activity of intermittently released PTH from scaffolds. PMID:26343649

  10. Influence of Parathyroid Hormone-Loaded PLGA Nanoparticles in Porous Scaffolds for Bone Regeneration.

    PubMed

    Gentile, Piergiorgio; Nandagiri, Vijay Kumar; Pabari, Ritesh; Daly, Jacqueline; Tonda-Turo, Chiara; Ciardelli, Gianluca; Ramtoola, Zebunnissa

    2015-08-28

    Biodegradable poly(lactide-co-glycolide) (PLGA) nanoparticles, containing human parathyroid hormone (PTH (1-34)), prepared by a modified double emulsion-solvent diffusion-evaporation method, were incorporated in porous freeze-dried chitosan-gelatin (CH-G) scaffolds. The PTH-loaded nanoparticles (NPTH) were characterised in terms of morphology, size, protein loading, release kinetics and in vitro assessment of biological activity of released PTH and cytocompatibility studies against clonal human osteoblast (hFOB) cells. Structural integrity of incorporated and released PTH from nanoparticles was found to be intact by using Tris-tricine SDS-PAGE. In vitro PTH release kinetics from PLGA nanoparticles were characterised by a burst release followed by a slow release phase for 3-4 weeks. The released PTH was biologically active as evidenced by the stimulated release of cyclic AMP from hFOB cells as well as increased mineralisation studies. in vitro and cell studies demonstrated that the PTH bioactivity was maintained during the fabrication of PLGA nanoparticles and upon release. Finally, a content of 33.3% w/w NPTHs was incorporated in CH-G scaffolds, showing an intermittent release during the first 10 days and, followed by a controlled release over 28 days of observation time. The increased expression of Alkaline Phosphatase levels on hFOB cells further confirmed the activity of intermittently released PTH from scaffolds.

  11. Controlled release of a sparingly water-soluble anticancer drug through pH-responsive functionalized gold-nanoparticle-decorated liposomes.

    PubMed

    Adhikari, Chandan; Das, Anupam; Chakraborty, Anjan

    2015-03-16

    The binding and detachment of carboxyl-modified gold nanoparticles from liposomes is used for controlled drug delivery. This study reveals that the binding and detachment of nanoparticles from liposomes depends on the degree of hydration of the liposomes. Liposomes with a lower hydration level undergo stronger electrostatic interactions with negatively charged gold nanoparticles, thus leading to a slower detachment of the carboxyl-modified gold nanoparticles under gastric conditions. Therefore, under gastric conditions, gold-nanoparticle-decorated dipalmitoylphosphatidylcholine (DPPC) liposomes exhibit an at least ten-times-slower drug release compared to gold-nanoparticle-decorated 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) liposomes, although both liposomes in the bare state fail to pursue controlled release. Our study also reveals that one can modulate the drug-release rate by simply varying the concentration of nanoparticles. This study highlights a novel strategy for the controlled release of drug molecules from liposomes.

  12. Synthesis of oxime-based CO-releasing molecules, CORMs and their immobilization on maghemite nanoparticles for magnetic-field induced CO release.

    PubMed

    Meyer, Hajo; Brenner, Markus; Höfert, Simon-P; Knedel, Tim-O; Kunz, Peter C; Schmidt, Annette M; Hamacher, Alexandra; Kassack, Matthias U; Janiak, Christoph

    2016-05-01

    Oxime-based CO-releasing molecules (oximeCORMs) were immobilized with a catechol-modified backbone on maghemite iron oxide nanoparticles (IONPs) to give oximeCORM@IONP. The CO release from the free and immobilized oximeCORMs was measured using the standard myoglobin assay. The oximeCORM-nanoparticles were coated with dextran for improved water solubility and confined into an alginate shell for protection and separation from the surrounding myoglobin assay to allow for CO release studies by UV/Vis absorption without interference from highly-absorptive oximeCORM@IONP. Half-lifes of the oxime-based polymer-confined alginate@dextran@oximeCORM@IONPs were estimated at 20 °C to 814 ± 23 min, at 37 °C to 346 ± 83 min and at 50 °C to 73 ± 1 min. The alginate@dextran@oximeCORM@IONP composite showed a further decrease of the half-life of CO release to 153 ± 27 min at 37 °C through local magnetic heating of the susceptible iron oxide nanoparticles with application of an external alternating magnetic field (31.7 kA m(-1), 247 kHz, 39.9 mTesla). The activation energy for the CO release from molecular dicarbonylchlorido(imidazole-2-carbaldehydeoxime)(alkoxycarbonyl)ruthenium(ii) complexes is determined to be ∼100 kJ mol(-1) for five different imidazole-oxime derivatives. PMID:27048982

  13. Multifunctional yolk-in-shell nanoparticles for pH-triggered drug release and imaging

    PubMed Central

    Chen, Hongyu; Qi, Bin; Moore, Thomas; Wang, Fenglin; Colvin, Daniel C.; Sanjeewa, Liurukara D.; Gore, John C.; Hwu, Shiou-Jyh; Mefford, O. Thompson; Alexis, Frank; Anker, Jeffrey N.

    2015-01-01

    Multifunctional nanoparticles are synthesized for both pH-triggered drug release and imaging with radioluminescence, upconversion luminescent, and magnetic resonance imaging (MRI). The particles have a yolk-in-shell morphology, with a radioluminescent core, an upconverting shell, and a hollow region between the core and shell for loading drugs. They are synthesized by controlled encapsulation of a radioluminescent nanophosphor yolk in a silica shell, partial etching of the yolk in acid, and encapsulation of the silica with an upconverting luminescent shell. Metroxantrone, a chemotherapy drug, was loaded into the hollow space between X-ray phosphor yolk and up-conversion phosphor shell through pores in the shell. To encapsulate the drug and control the release rate, the nanoparticles are coated with pH-responsive biocompatible polyelectrolyte layers of charged hyaluronic acid sodium salt and chitosan. The nanophosphors display bright luminescence under X-ray, blue light (480 nm), and infrared light (980 nm). They also served as T1 and T2 MRI contrast agents with relaxivities of 3.5 mM−1 s−1 (r1) and 64 mM−1s−1 (r2). These multifunctional nanocapsules have applications in controlled drug delivery and multimodal imaging. PMID:24753264

  14. Utilizing the protein corona around silica nanoparticles for dual drug loading and release.

    PubMed

    Shahabi, Shakiba; Treccani, Laura; Dringen, Ralf; Rezwan, Kurosch

    2015-10-21

    A protein corona forms spontaneously around silica nanoparticles (SNPs) in serum-containing media. To test whether this protein corona can be utilized for the loading and release of anticancer drugs we incorporated the hydrophilic doxorubicin, the hydrophobic meloxicam as well as their combination in the corona around SNPs. The application of corona-covered SNPs to osteosarcoma cells revealed that drug-free particles did not affect the cell viability. In contrast, SNPs carrying a protein corona with doxorubicin or meloxicam lowered the cell proliferation in a concentration-dependent manner. In addition, these particles had an even greater antiproliferative potential than the respective concentrations of free drugs. The best antiproliferative effects were observed for SNPs containing both doxorubicin and meloxicam in their corona. Co-localization studies revealed the presence of doxorubicin fluorescence in the nucleus and lysosomes of cells exposed to doxorubicin-containing coated SNPs, suggesting that endocytotic uptake of the SNPs facilitates the cellular accumulation of the drug. Our data demonstrate that the protein corona, which spontaneously forms around nanoparticles, can be efficiently exploited for loading the particles with multiple drugs for therapeutic purposes. As drugs are efficiently released from such particles they may have a great potential for nanomedical applications.

  15. Improving Cancer Chemoradiotherapy Treatment by Dual Controlled Release of Wortmannin and Docetaxel in Polymeric Nanoparticles.

    PubMed

    Au, Kin Man; Min, Yuanzeng; Tian, Xi; Zhang, Longzhen; Perello, Virginia; Caster, Joseph M; Wang, Andrew Z

    2015-09-22

    Combining molecularly targeted agents and chemotherapeutics is an emerging strategy in cancer treatment. We engineered sub-50 nm diameter diblock copolymer nanoparticles (NPs) that can sequentially release wortmannin (Wtmn, a cell signaling inhibitor) and docetaxel (Dtxl, genotoxic anticancer agent) to cancer cells. These NPs were studied in chemoradiotherapy, an important cancer treatment paradigm, in the preclinical setting. We demonstrated that Wtmn enhanced the therapeutic efficacy of Dtxl and increased the efficiency of radiotherapy (XRT) in H460 lung cancer and PC3 prostate cells in culture. Importantly, we showed that NPs containing both Wtmn and Dtxl release the drugs in a desirable sequential fashion to maximize therapeutic efficacy in comparison to administering each drug alone. An in vivo toxicity study in a murine model validated that NPs containing both Dtxl and Wtmn do not have a high toxicity profile. Lastly, we demonstrated that Dtxl/Wtmn-coencapsulated NPs are more efficient than each single-drug-loaded NPs or a combination of both single-drug-loaded NPs in chemoradiotherapy using xenograft models. Histopathological studies and correlative studies support that the improved therapeutic efficacy is through changes in signaling pathways and increased tumor cell apoptosis. Our findings suggest that our nanoparticle system led to a dynamic rewiring of cellular apoptotic pathways and thus improve the therapeutic efficiency.

  16. Biocompatible thermoresponsive PEGMA nanoparticles crosslinked with cleavable disulfide-based crosslinker for dual drug release.

    PubMed

    Ulasan, Mehmet; Yavuz, Emine; Bagriacik, Emin Umit; Cengeloglu, Yunus; Yavuz, Mustafa Selman

    2015-01-01

    Smart materials have been attracting much attention because of their stimuli responsive nature. We have synthesized biocompatible thermoresponsive crosslinked poly(ethylene glycol) methyl ether methacrylate (PEGMA)-co-vinyl pyrrolidone nanoparticles (PEGMA NPs) using disulfide-based crosslinker by surfactant-free emulsion polymerization method. Particle characterization studies were carried out by dynamic light scattering, and scanning electron microscopy. Polymerization kinetics, effect of crosslinker and initiator concentrations on both average hydrodynamic diameter and polydispersity index were investigated. Hydrodynamic diameters of thermoresponsive PEGMA NPs were decreased from 210 nm to 90 nm upon heating over the lowest critical solution temperature (LCST). Disulfide crosslinked PEGMA NPs were demonstrated as a dual delivery system. Rhodamine B, a model of small-sized drug molecule, and poly(ethylene glycol) (PEG)-alizarin yellow, a model of large drug molecule, were loaded into PEGMA NPs where LCST of these NPs was tuned to 37°C, the body temperature. The rhodamine B was released from PEGMA NPs upon heating to 39°C. Then, PEG-alizarin content was released by subsequent degradation of nanoparticles using dithiothreitol (DTT), which reduces disulfide bonds to thiols. Furthermore, cytotoxicity studies of PEGMA NPs were carried out in 3T3 cells, which resulted in no toxic effect on the cells.

  17. Chitosan magnetic nanoparticles for pH responsive Bortezomib release in cancer therapy.

    PubMed

    Unsoy, Gozde; Yalcin, Serap; Khodadust, Rouhollah; Mutlu, Pelin; Onguru, Onder; Gunduz, Ufuk

    2014-06-01

    The use of nanotechnology in cancer treatment offers exciting opportunities, including the possibility of destroying tumors with minimal damage to healthy tissue by novel targeted drug delivery systems. pH differences between healthy and tumor microenvironment provide pH responsive release of drugs at tumor site via smart nanoparticles. In this study, chitosan coated superparamagnetic iron oxide nanoparticles (CS MNPs) were in situ synthesized by ionic crosslinking method as nanocarrier systems and loaded with the drug Bortezomib (Velcade(®)). The drug loading capacity, drug release and stability of CS MNPs were analyzed. CS MNPs were visualized inside the cells by fluorescence microscopy. The cytotoxicity of Bortezomib, CS MNPs and Bortezomib loaded CS MNPs were tested by XTT analyses in vitro. Gene expression analyses revealed that pro-apoptotic PUMA and NOXA genes were upregulated while anti-apoptotic BCL-2, SURVIVIN and cIAP-2 genes were downregulated at Bortezomib loaded CS MNP treated cells. Immunocytochemical analyses demonstrated an increase in p53 tumor suppressor protein levels at treated cells, which supports the upregulation of PUMA and NOXA genes, while Survivin protein level did not significantly change. This study points out that the pH responsive magnetic targeting of Bortezomib is more efficacious than free drug treatment. Moreover, targeted delivery of Bortezomib would reduce the frequency of drug administration by lowering the required amount of drug dose.

  18. Development and physical characterization of chloramphenicol loaded biodegradable nanoparticles for prolonged release.

    PubMed

    Mandal, B; Halder, K K; Dey, S K; Bhoumik, M; Debnath, M C; Ghosh, L K

    2009-07-01

    The objectives of our study were to prepare a biodegradable nanoparticulate system of chloramphenicol (CHL) and to evaluate its ability to prolong in vitro release of CHL compared to free drug suspension (FDS). CHL-loaded polylactide-co-glycolide nanoparticles (CHL-PLGA-NPs) were prepared by an emulsion/solvent evaporation method using ethyl acetate and polyvinyl alcohol. CHL-PLGA-NPs were characterized by particle size, zeta potential, infrared spectra, drug entrapment efficiency and in vitro release kinetics measurement. Sonication was done with an ultrasound pulse sonicator at 70 W, 30 kHz for 60 s to produce stable NPs of mean size range from 277 nm to 433 nm. Drug to polymer ratio (D:P) was selected as formulation variable and significantly influenced entrapment efficiency (approximately 30% to 66%) and release (p < 0.05). Entrapment of CHL in biodegradable NPs significantly prolonged drug release compared to FDS and thus implies potential antibiotic delivery system for ocular application.

  19. Textile Functionalization and Its Effects on the Release of Silver Nanoparticles into Artificial Sweat.

    PubMed

    Wagener, Sandra; Dommershausen, Nils; Jungnickel, Harald; Laux, Peter; Mitrano, Denise; Nowack, Bernd; Schneider, Gregor; Luch, Andreas

    2016-06-01

    This study addresses the release of total silver (Ag) and silver nanoparticles (Ag-NPs) from textiles into artificial sweat, particularly considering the functionalization technology used in textile finishing. Migration experiments were conducted for four commercially available textiles and for six laboratory-prepared textiles. Two among these lab-prepared textiles represent materials in which Ag-NPs were embedded within the textile fibers (composites), whereas the other lab-prepared textiles contain Ag particles on the respective fiber surfaces (coatings). The results indicate a smaller release of total Ag from composites in comparison to surface-coated textiles. The particulate fraction determined within the artificial sweat was negligible for most textiles, meaning that the majority of the released Ag is present as dissolved Ag. It is also relevant to note that nanotextiles do not release more particulate Ag than conventional Ag textiles. The results rather indicate that the functionalization type is the most important parameter affecting the migration. Furthermore, after measuring different Ag-NP types in their pristine form with inductively coupled plasma mass spectrometry in the single particle mode, there is evidence that particle modifications, like surface coating, may also influence the dissolution behavior of the Ag-NPs in the sweat solutions. These factors are important when discussing the likelihood of consumer exposure.

  20. Magnetically stimulated ciprofloxacin release from polymeric microspheres entrapping iron oxide nanoparticles

    PubMed Central

    Sirivisoot, Sirinrath; Harrison, Benjamin S

    2015-01-01

    To extend the external control capability of drug release, iron oxide nanoparticles (NPs) encapsulated into polymeric microspheres were used as magnetic media to stimulate drug release using an alternating magnetic field. Chemically synthesized iron oxide NPs, maghemite or hematite, and the antibiotic ciprofloxacin were encapsulated together within polycaprolactone microspheres. The polycaprolactone microspheres entrapping ciprofloxacin and magnetic NPs could be triggered for immediate drug release by magnetic stimulation at a maximum value of 40%. Moreover, the microspheres were cytocompatible with fibroblasts in vitro with a cell viability percentage of more than 100% relative to a nontreated control after 24 hours of culture. Macrophage cell cultures showed no signs of increased inflammatory responses after in vitro incubation for 56 hours. Treatment of Staphylococcus aureus with the magnetic microspheres under an alternating (isolating) magnetic field increased bacterial inhibition further after 2 days and 5 days in a broth inhibition assay. The findings of the present study indicate that iron oxide NPs, maghemite and hematite, can be used as media for stimulation by an external magnetic energy to activate immediate drug release. PMID:26185446

  1. Sustained PDGF-BB release from PHBHHx loaded nanoparticles in 3D hydrogel/stem cell model.

    PubMed

    Dong, Cui-Ling; Webb, William R; Peng, Qiang; Tang, James Z; Forsyth, Nicholas R; Chen, Guo-Qiang; El Haj, Alicia J

    2015-01-01

    This study aimed to design a growth factor loaded copolyester of 3-hydroxybutyrate and 3-hydroxyhexanoate (PHBHHx) nanoparticles containing 3D collagen matrix to achieve growth factor sustained release for long-term stimulation of human mesenchymal stem cells (hMSCs) proliferation/differentiation for tissue engineer application. Platelet-derived growth factor-BB (PDGF-BB), which is known to enhance hMSCs proliferation in human serum, was selected as a model growth factor, and biodegradable copolyester of PHBHHx was chosen to be the sustained release vehicle. PDGF-BB phospholipid complex encapsulated PHBHHx nanoparticles were fabricated, and their effect on hMSCs proliferation was investigated via assays of CCK-8 and live-dead staining to cells inoculated in 2D tissue culture plates and 3D collagen gel scaffolds, respectively. The resulting spherical PHBHHx nanoparticles were stable in terms of their mean particle size, polydispersity index and zeta potential before and after lyophilization. In vitro study revealed a sustained release of PDGF-BB with a low burst release. Furthermore, sustained released PDGF-BB was revealed to significantly promote hMSCs proliferation in both cell monolayer and cell seeded 3D collagen scaffolds inoculated in serum-free media. Therefore, the 3D collagen matrices with locally sustained release growth factor nanoparticles hold promise to be used for stem cell tissue engineering.

  2. Tunable Controlled Release of Bioactive SDF-1α via Protein Specific Interactions within Fibrin/Nanoparticle Composites

    PubMed Central

    Dutta, D.; Fauer, C.; Mulleneux, H.L.; Stabenfeldt, S. E.

    2015-01-01

    The chemokine, stromal cell-derived factor 1α (SDF-1α), is a key regulator of the endogenous neural progenitor/stem cell-mediated regenerative response after neural injury. Increased and sustained bioavailability of SDF-1α in the peri-injury region is hypothesized to modulate this endogenous repair response. Here, we describe poly(lactic-co-glycolic) acid (PLGA) nanoparticles capable of releasing bioactive SDF-1α in a sustained manner over 60days after a burst of 23%. Moreover, we report a biphasic cellular response to SDF-1α concentrations thus the large initial burst release in an in vivo setting may result in supratherapeutic concentrations of SDF-1α. Specific protein-protein interactions between SDF-1α and fibrin (as well as its monomer, fibrinogen) were exploited to control the magnitude of the burst release. Nanoparticles embedded in fibrin significantly reduced the amount of SDF-1α released after 72 hrs as a function of fibrin density. Therefore, the nanoparticle/fibrin composites represented a means to independently tune the magnitude of the burst phase release from the nanoparticles while perserving a bioactive depot of SDF-1α for release over 60days. PMID:26660666

  3. Light-Triggered Release from Pickering Emulsions Stabilized by TiO2 Nanoparticles with Tailored Wettability.

    PubMed

    Bai, Rui-Xue; Xue, Long-Hui; Dou, Rong-Kun; Meng, Shi-Xin; Xie, Chun-Yan; Zhang, Qing; Guo, Ting; Meng, Tao

    2016-09-13

    In this work, a new strategy for developing light-triggered Pickering emulsions as smart soft vehicles for on-demand release is proposed. Initially, UV-induced tailored wettability allows anchoring of TiO2 nanoparticles at the interface to prepare stable water in oil emulsions. Such emulsions show the efficacy of microencapsulation and controlled release by demulsification due to the hydrophilic conversion of the TiO2 nanoparticles using a noninvasive light irradiation trigger. A molecule of interest is selected as a model cargo to quantitatively evaluate the as-prepared Pickering emulsions for their encapsulation and release behaviors. Moreover, light-responsive emulsion destabilization mechanism is studied as a function of particle concentration, light wavelength, and light intensity, respectively, determined by drop diameter evolution and droplet coalescence kinetics plots. For consideration of application in life sciences, Pickering emulsions sensitive to visible light are also established based on nitrogen doping of TiO2 nanoparticle emulsifiers. PMID:27505101

  4. Light-Triggered Release from Pickering Emulsions Stabilized by TiO2 Nanoparticles with Tailored Wettability.

    PubMed

    Bai, Rui-Xue; Xue, Long-Hui; Dou, Rong-Kun; Meng, Shi-Xin; Xie, Chun-Yan; Zhang, Qing; Guo, Ting; Meng, Tao

    2016-09-13

    In this work, a new strategy for developing light-triggered Pickering emulsions as smart soft vehicles for on-demand release is proposed. Initially, UV-induced tailored wettability allows anchoring of TiO2 nanoparticles at the interface to prepare stable water in oil emulsions. Such emulsions show the efficacy of microencapsulation and controlled release by demulsification due to the hydrophilic conversion of the TiO2 nanoparticles using a noninvasive light irradiation trigger. A molecule of interest is selected as a model cargo to quantitatively evaluate the as-prepared Pickering emulsions for their encapsulation and release behaviors. Moreover, light-responsive emulsion destabilization mechanism is studied as a function of particle concentration, light wavelength, and light intensity, respectively, determined by drop diameter evolution and droplet coalescence kinetics plots. For consideration of application in life sciences, Pickering emulsions sensitive to visible light are also established based on nitrogen doping of TiO2 nanoparticle emulsifiers.

  5. Release of anti-inflammatory peptides from thermosensitive nanoparticles with degradable cross-links suppresses pro-inflammatory cytokine production.

    PubMed

    Poh, Scott; Lin, Jenny B; Panitch, Alyssa

    2015-04-13

    Pro-inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) are mediators in the development of many inflammatory diseases. To demonstrate that macrophages take up and respond to thermosensitive nanoparticle drug carriers, we synthesized PEGylated poly(N-isopropylacrylamide-2-acrylamido-2-methyl-1-propanesulfonate) particles cross-linked with degradable disulfide (N,N'-bis(acryloyl)cystamine) (NGPEGSS). An anti-inflammatory peptide (KAFAK) was loaded and released from the thermosensitive nanoparticles and shown to suppress levels of TNF-α and IL-6 production in macrophages. Cellular uptake of fluorescent, thermosensitive, and degradable nanoparticles and therapeutic efficacy of free KAFAK peptide compared to that of KAFAK loaded in PEGylated degradable thermosensitive nanoparticles were examined. The data suggests that the degradable, thermosensitive nanoparticles loaded with KAFAK may be an effective tool to treat inflammatory diseases.

  6. MgAl- Layered Double Hydroxide Nanoparticles for controlled release of Salicylate.

    PubMed

    Mondal, Soumini; Dasgupta, Sudip; Maji, Kanchan

    2016-11-01

    Layered double hydroxides (LDHs), have been known for many decades as catalyst and ceramic precursors, traps for anionic pollutants, and additives for polymers. Recently, their successful synthesis on the nanometer scale opened up a whole new field for their application in nanomedicine. Here we report the efficacy of Mg1-xAlx (NO3)x (OH)2 LDH nanoparticles as a carrier and for controlled release of one of the non-steroidal anti-inflammatory drugs (NSAID), sodium salicylate. Mg1-xAlx (NO3)x (OH)2.nH2O nanoparticles were synthesized using co-precipitation method from an aqueous solution of Mg(NO3)2.6H2O and Al(NO3)3.9H2O. Salicylate was intercalated in the interlayer space of Mg-Al LDH after suspending nanoparticles in 0.0025(M) HNO3 and 0.75 (M) NaNO3 solution and using anion exchange method under N2 atmosphere. The shift in the basal planes like (003) and (006) to lower 2θ value in the XRD plot of intercalated sample confirmed the increase in basal spacing in LDH because of intercalation of salicylate into the interlayer space of LDH. FTIR spectroscopy of SA-LDH nano hybrid revealed a red shift in the frequency band of carboxylate group in salicylate indicating an electrostatic interaction between cationic LDH sheet and anionic drug. Differential thermal analysis of LDH-SA nanohybrid indicated higher thermal stability of salicylate in the intercalated form into LDH as compared to its free state. DLS studies showed a particle size distribution between 30-60 nm for pristine LDH whereas salicylate intercalated LDH exhibited a particle size distribution between 40-80nm which is ideal for its efficacy as a superior carrier for drugs and biomolecules. The cumulative release kinetic of salicylate from MgAl-LDH-SA hybrids in phosphate buffer saline (PBS) at pH7.4 showed a sustained release of salicylate up to 72h that closely resembled first order release kinetics through a combination of drug diffusion and dissolution of LDH under physiological conditions. Also the

  7. Fine-tuning in mineral cross-linking of biopolymer nanoparticle for incorporation and release of cargo.

    PubMed

    Fukui, Yuuka; Kabayama, Narumi; Fujimoto, Keiji

    2015-12-01

    We developed a mineral cross-linking strategy to prepare a biopolymer-based nanoparticle using calcium phosphate (CaP) as a cross-linker. Nanoparticles were first formed by mixing deoxyribonucleic acid (DNA) with cationic surfactants, and were cross-linked by CaP precipitation. After removal of the surfactants, we carried out the alternative dialysis of nanoparticles against CaCl2 aqueous solution and phosphate buffered solution for further mineral cross-linking. XRD and FT-IR studies revealed that the resultant nanoparticles were produced by mineral cross-linkages of hydroxyapatite (HAp) and the crystal amount and properties such as morphology and crystallinity could be well-controlled by the reaction conditions. Chemical dyes could be incorporated into nanoparticles via their affinities with crystal faces of HAp and DNA. Their release was tunable by crystal amount and properties of mineral cross-linkages. Also, the release could be triggered by mineral dissolution in response to pH. Such a mineral cross-linking will open up a potential way to provide a nanoparticle with versatile functions such as cleavable cross-linking, binding affinity for cargos, and pH-responsive release. PMID:26387068

  8. Nanoparticles based on star polymers as theranostic vectors: endosomal-triggered drug release combined with MRI sensitivity.

    PubMed

    Li, Yang; Duong, Hien T T; Laurent, Sophie; MacMillan, Alexandre; Whan, Renee Megan; Elst, Luce Vander; Muller, Robert N; Hu, Jinming; Lowe, Andrew; Boyer, Cyrille; Davis, Thomas P

    2015-01-01

    Dual-functional star polymers (diameters 15 nm) are synthesized producing nanoparticles with excellent colloidal stability in both water and serum. The nanoparticles are built with aldehyde groups in the core and activated esters in the arms. The different reactivity of the two functional groups to sequentially react with different amino compounds is exploited; doxorubicin (DOX) and 1-(5-amino-3-aza-2-oxypentyl)-4,7,10-tris(tert-butoxycarbonylmethyl)-1,4,7,10-tetraazacyclododecane (DO3A-tBu-NH2 )-a chelating agent effective for the complexation of Gadolinium ions (Gd). The activated ester group is employed to attach the DO3A chelating agent, while the aldehyde groups are exploited for DOX conjugation, providing a controlled release mechanism for DOX in acidic environments. DOX/Gd-loaded nanoparticles are rapidly taken up by MCF-7 breast cancer cells, subsequently releasing DOX as demonstrated using in vitro fluorescence lifetime imaging microscopy (FLIM). Endosomal, DOX release is observed, using a phasor plot representation of the fluorescence lifetime data, showing an increase of native DOX with time. The MRI properties of the stars are assessed and the relaxivity of Gd loaded in stars is three times higher than conventional organic Gd/DO3A complexes. The DOX/Gd-conjugated nanoparticles yield a similar IC50 to native DOX for breast cancer cell lines, confirming that DOX integrity is conserved during nanoparticle attachment and release.

  9. Extended release of ketotifen from silica shell nanoparticle-laden hydrogel contact lenses: in vitro and in vivo evaluation.

    PubMed

    Maulvi, Furqan A; Mangukiya, Mayurkumar A; Patel, Prachi A; Vaidya, Rutvi J; Koli, Akshay R; Ranch, Ketan M; Shah, Dinesh O

    2016-06-01

    Ketotifen an anti-allergic drug delivered via eye drops has major limitations, including poor ocular bioavailability and poor patient compliance. The objective of the research work was to fabricate ketotifen loaded microemulsion laden hydrogels and silica shell nanoparticle-laden (prepared from microemulsion using octyltrimethoxysilane) hydrogels to achieve extended ocular drug delivery. The porous silica shell membrane was synthesized at the liquid interface of microemulsion, which facilitates the prolongation of drug release duration from hydrogels. Drug encapsulated microemulsion and silica shell nanoparticles were dispersed separately in pre-monomer mixture, and fabricated to hydrogel. For comparison, hydrogel with direct drug entrapment was also fabricated. Significant loss in transmittance and physical properties was observed in hydrogels with direct drug entrapment. While, microemulsion and silica shell nanoparticle-laden hydrogels did not show significant effect on transmittance and physical properties. The in vitro drug release data showed extended release of ketotifen from hydrogels in following order: direct loadingnanoparticles. The results of cytotoxicity and animal study confirmed the safety of hydrogels. The in vivo pharmacokinetic study showed extended ketotifen release for more than 10 days. The results demonstrated the translational potential of silica shell nanoparticles for extended drug delivery without compromising the critical lens properties. PMID:27178036

  10. Construction and evaluation of controlled-release delivery system of Abamectin using porous silica nanoparticles as carriers

    NASA Astrophysics Data System (ADS)

    Wang, Yan; Cui, Haixin; Sun, Changjiao; Zhao, Xiang; Cui, Bo

    2014-12-01

    Photolysis and poor solubility in water of Abamectin are key issues to be addressed, which causes low bioavailability and residual pollution. In this study, a novel hydrophilic delivery system through loading Abamectin with porous silica nanoparticles (Abam-PSNs) was developed in order to improve the chemical stability, dispersity, and the controlled release of Abamectin. These results suggest that Abam-PSNs can significantly improve the performance of controllable release, photostability, and water solubility of Abamectin by changing the porous structure of silica nanoparticles, which is favorable to improve the bioavailability and reduce the residues of pesticides.

  11. Intelligent Janus nanoparticles for intracellular real-time monitoring of dual drug release

    NASA Astrophysics Data System (ADS)

    Cao, Han; Yang, Yuhong; Chen, Xin; Shao, Zhengzhong

    2016-03-01

    Stimuli-responsive nanomaterials have been receiving much attention as drug delivery carriers, however understanding of multi-drug release from the carriers for efficient therapeutics is highly challenging. Here, we report a novel nanosystem, Janus particle Dox-CMR-MS/Au-6MP (Dox: doxorubicin, CMR: 7-hydroxycoumarin-3-carboxylate, MS: mesoporous silica, Au: gold, 6MP: 6-mercaptopurine) with opposing MS and Au faces, which can monitor intracellular dual-drug (Dox and 6MP) controlled release in real time based on fluorescence resonance energy transfer (FRET) and surface-enhanced Raman scattering (SERS). The FRET acceptor Dox is attached to CMR (as a FRET donor) conjugated MS with a pH-responsive linker hydrazone, and 6MP is conjugated to the Au surface through the gold-thiol interaction. As the Janus nanoparticle enters into tumor cells, the breakage of the hydrazone bond in an acidic environment and the substitution of glutathione (GSH) overexpressed in cancer cells give rise to the release of Dox and 6MP, respectively. Thus, the change of the CMR fluorescence signal and the SERS decrease of 6MP can be used to monitor the dual-drug release within living cells in real time. In addition, this work demonstrates the enhanced anticancer effect of the designed dual-drug loaded nanosystem. Therefore, the current study may provide new perspectives for the real-time study of intelligent multi-drug delivery and release, as well as cellular responses to drug treatment.Stimuli-responsive nanomaterials have been receiving much attention as drug delivery carriers, however understanding of multi-drug release from the carriers for efficient therapeutics is highly challenging. Here, we report a novel nanosystem, Janus particle Dox-CMR-MS/Au-6MP (Dox: doxorubicin, CMR: 7-hydroxycoumarin-3-carboxylate, MS: mesoporous silica, Au: gold, 6MP: 6-mercaptopurine) with opposing MS and Au faces, which can monitor intracellular dual-drug (Dox and 6MP) controlled release in real time based on

  12. Cross-linked gelatin/nanoparticles composite coating on micro-arc oxidation film for corrosion and drug release

    NASA Astrophysics Data System (ADS)

    Xu, Xinhua; Lu, Ping; Guo, Meiqing; Fang, Mingzhong

    2010-02-01

    A composite coating which could control drug release and biocorrosion of magnesium alloy stent materials WE42 was prepared. This composite coating was fabricated on the surface of the micro-arc oxidation (MAO) film of the magnesium alloy, WE42, by mixing different degrees of cross-linked gelatin with well-dispersed poly( DL-lactide-co-glycolide) (PLGA) nanoparticles. The PLGA nanoparticles were prepared by emulsion solvent evaporation/extraction technique. Nano ZS laser diffraction particle size analyzer detected that the size of the nanoparticles to be 150-300 nm. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) was used to analyze the morphology of the nanoparticles and the composite coating. Potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) were used to evaluate the corrosion behavior of the composite coating. Drug release was determined by ultraviolet-visible (UV-vis) spectrophotometer. The corrosion resistance of the composite coating was improved by preventing the corrosive ions from diffusing to the MAO films. The drug release rate of paclitaxel (PTX) exhibited a nearly linear sustained-release profile with no significant burst releases.

  13. Control-release microcapsule of famotidine loaded biomimetic synthesized mesoporous silica nanoparticles: Controlled release effect and enhanced stomach adhesion in vitro.

    PubMed

    Li, Jing; Wang, Hongyu; Yang, Baixue; Xu, Lu; Zheng, Nan; Chen, Hongtao; Li, Sanming

    2016-01-01

    In the present work, control-release microcapsule of famotidine (FMT) loaded biomimetic synthesized mesoporous silica nanoparticles (B-MSNs) was developed, and controlled release effect and stomach adhesion of this formulation in vitro were mainly investigated. B-MSN was previously synthesized and it was amorphous mesoporous nanoparticles with helical channels. Cytotoxicity of B-MSN was studied using human breast cancer cells (MCF-7) and the result indicated that cytotoxicity of B-MSN can be neglected. After loading FMT into B-MSN, specific surface area, pore volume and pore diameter of B-MSN were obviously reduced. In vitro dissolution test showed that B-MSN had the ability to slow down FMT release for 15 min. In order to prolong controlled release effect and remained the advantage of B-MSN (improve drug stability due to its rigid silica framework), the combined application of control-release microcapsule (using cellulose and hydroxypropyl methylcellulose K15M as excipients) with B-MSN was designed. It was obvious that newly designed formulation significantly controlled FMT release with Fickian diffusion mechanism and showed enhanced stomach adhesion in vitro, which has significant value in widening the application of B-MSN in formulation design.

  14. Designer nanoparticles: Incorporating size, shape, and triggered release into nanoscale drug carriers

    PubMed Central

    Caldorera-Moore, Mary; Guimard, Nathalie; Shi, Li; Roy, Krishnendu

    2009-01-01

    Importance of the field Although significant progress has been made in delivering therapeutic agents through micro and nanocarriers, precise control over in vivo biodistribution and disease-responsive drug release has been difficult to achieve. This is critical for the success of next generation drug delivery devices, since newer drugs, designed to interfere with cellular functions, must be efficiently and specifically delivered to diseased cells. The major constraint in achieving this has been our limited repertoire of particle synthesis methods, especially at the nanoscale. Recent developments in generating shape-specific nanocarriers and the potential to combine stimuli-responsive release with nanoscale delivery devices show great promise in overcoming these limitations. Areas covered in this review Here we discuss how recent advancements in fabrication technology allow synthesis of highly monodisperse, stimuli-responsive, drug-carrying nanoparticles of precise geometries. We also review how particle properties, specifically shape and stimuli responsiveness, affect biodistribution, cellular uptake, and drug release. What the reader will gain The reader is introduced to recent developments in intelligent drug nanocarriers and new nanofabrication approaches that can be combined with disease-responsive biomaterials. This will provide insight into the importance of controlling particle geometry and incorporating stimuli responsive materials into drug delivery. PMID:20331355

  15. Morphological, physical, antimicrobial and release properties of ZnO nanoparticles-loaded bacterial cellulose films.

    PubMed

    Shahmohammadi Jebel, Fereshteh; Almasi, Hadi

    2016-09-20

    Bacterial cellulose (BC) monolayer and multilayer films, incorporating 5wt.% ZnO nanoparticles (NPs) have been obtained. Ultrasound (US) irradiation (40kHz) was applied during ZnO-BC nanocomposites preparation. X-ray diffraction (XRD) patterns showed that ZnO NPs were crystallized in their pure phase. SEM scanning electron microscopy (SEM) results indicated that US treatment causes to decrease ZnO particle size, forming a stable hybrid nanostructure and evenly distributed ZnO NPs coated BC nanofibers. ZnO NPs enhanced the mechanical properties and diminished water vapor permeability and moisture absorption of BC films. Antibacterial activity of ZnO-BC films against Staphylococcus aureus was more than Escherichia coli. The antibacterial activity was enhanced with the utilization of US irradiation. The ZnO release was influenced by films composition; the multilayer and US treated films being promising in order to achieve controlled release of ZnO. Results suggest that ZnO-BC films may be used as controlled release antimicrobial food active packaging. PMID:27261725

  16. pH-sensitive strontium carbonate nanoparticles as new anticancer vehicles for controlled etoposide release

    PubMed Central

    Qian, Wen-Yu; Sun, Dong-Mei; Zhu, Rong-Rong; Du, Xi-Ling; Liu, Hui; Wang, Shi-Long

    2012-01-01

    Strontium carbonate nanoparticles (SCNs), a novel biodegradable nanosystem for the pH-sensitive release of anticancer drugs, were developed via a facile mixed solvent method aimed at creating smart drug delivery in acidic conditions, particularly in tumor environments. Structural characterization of SCNs revealed that the engineered nanocarriers were uniform in size and presented a dumbbell-shaped morphology with a dense mass of a scale-like spine coating, which could serve as the storage structure for hydrophobic drugs. Chosen as a model anticancer agent, etoposide was effectively loaded into SCNs based on a simultaneous process that allowed for the formation of the nanocarriers and for drug storage to be accomplished in a single step. The etoposide-loaded SCNs (ESCNs) possess both a high loading capacity and efficient encapsulation. It was found that the cumulative release of etoposide from ESCNs is acid-dependent, and that the release rate is slow at a pH of 7.4; this rate increases significantly at low pH levels (5.8, 3.0). Meanwhile, it was also found that the blank SCNs were almost nontoxic to normal cells, and ESCN systems were evidently more potent in antitumor activity compared with free etoposide, as confirmed by a cytotoxicity test using an MTT assay and an apoptosis test with fluorescence-activated cell sorter (FACS) analysis. These findings suggest that SCNs hold tremendous promise in the areas of controlled drug delivery and targeted cancer therapy. PMID:23185118

  17. Imaging-guided photoacoustic drug release and synergistic chemo-photoacoustic therapy with paclitaxel-containing nanoparticles.

    PubMed

    Zhong, Junping; Yang, Sihua; Wen, Liewei; Xing, Da

    2016-03-28

    Here, a novel triggered drug release modality was developed for oncotherapy. Paclitaxel (PTX), perfluorohexane (PFH) and gold nanorods (AuNRs) loaded nanoparticles (PTX-PAnP) were synthesized. Folic acid (FA) conjugated PTX-PAnP (PTX-PAnP-FA) could be selectively taken into folate receptor-overexpressed tumor cells. Upon pulsed laser irradiation, the PTX-PAnP-FA could be rapidly destructed because of the PFH vaporization, resulting in fast drug release, which induced apoptosis of cancer cells efficiently. Stimulated fragmentation of the PTX-PAnP-FA nanoparticles can facilitate multiple mechanisms such as bubble implosion, shockwave generation, and sonoporation that further enhance the therapeutic efficiency. The in vivo therapy study further confirmed this new approach resulted in efficient tumor suppression. The results demonstrate a unique drug release mechanism based on photoacoustic effect. It provides an all-in-one platform for photoacoustic image-guided drug release and synergistic chemo-photoacoustic therapy.

  18. Simultaneous spectroscopic measurements of the interior temperature and induced cargo release from pore-restricted mesoporous silica nanoparticles.

    PubMed

    Dong, Juyao; Zink, Jeffrey I

    2016-05-19

    Temperature changes initiated within nano structures are being increasingly used to externally activate responsive delivery vehicles. Yet, the precise measurement of the nano environment temperature increase and its correlation with the induced macroscopic cargo release are difficult to achieve. In this study, we focus on a photothermally activated drug delivery system based on mesoporous silica nanoparticles, and use an optical nanothermometer - NaYF4:Yb(3+),Er(3+) crystals - for a ratiometric temperature measurement. Using fluorescent dyes as the payload molecule, both the nanoparticle interior temperature change and the macroscopic cargo release amount are monitored simultaneously by fluorescent spectroscopy. We found that the cargo release lags the temperature increase by about 5 min, revealing the threshold temperature that the particles have to reach before a substantial release could happen. Using this spectroscopic method, we are able to directly compare and correlate a nano environment event with its stimulated macroscopic results.

  19. Stability, Intracellular Delivery, and Release of siRNA from Chitosan Nanoparticles Using Different Cross-Linkers

    PubMed Central

    Abdul Ghafoor Raja, Maria; Katas, Haliza; Jing Wen, Thum

    2015-01-01

    Chitosan (CS) nanoparticles have been extensively studied for siRNA delivery; however, their stability and efficacy are highly dependent on the types of cross-linker used. To address this issue, three common cross-linkers; tripolyphosphate (TPP), dextran sulphate (DS) and poly-D-glutamic acid (PGA) were used to prepare siRNA loaded CS-TPP/DS/PGA nanoparticles by ionic gelation method. The resulting nanoparticles were compared with regard to their physicochemical properties including particle size, zeta potential, morphology, binding and encapsulation efficiencies. Among all the formulations prepared with different cross linkers, CS-TPP-siRNA had the smallest particle size (ranged from 127 ± 9.7 to 455 ± 12.9 nm) with zeta potential ranged from +25.1 ± 1.5 to +39.4 ± 0.5 mV, and high entrapment (>95%) and binding efficiencies. Similarly, CS-TPP nanoparticles showed better siRNA protection during storage at 4˚C and as determined by serum protection assay. TEM micrographs revealed the assorted morphology of CS-TPP-siRNA nanoparticles in contrast to irregular morphology displayed by CS-DS-siRNA and CS-PGA-siRNA nanoparticles. All siRNA loaded CS-TPP/DS/PGA nanoparticles showed initial burst release followed by sustained release of siRNA. Moreover, all the formulations showed low and concentration-dependent cytotoxicity with human colorectal cancer cells (DLD-1), in vitro. The cellular uptake studies with CS-TPP-siRNA nanoparticles showed successful delivery of siRNA within cytoplasm of DLD-1 cells. The results demonstrate that ionically cross-linked CS-TPP nanoparticles are biocompatible non-viral gene delivery system and generate a solid ground for further optimization studies, for example with regard to steric stabilization and targeting. PMID:26068222

  20. Stability, Intracellular Delivery, and Release of siRNA from Chitosan Nanoparticles Using Different Cross-Linkers.

    PubMed

    Raja, Maria Abdul Ghafoor; Katas, Haliza; Jing Wen, Thum

    2015-01-01

    Chitosan (CS) nanoparticles have been extensively studied for siRNA delivery; however, their stability and efficacy are highly dependent on the types of cross-linker used. To address this issue, three common cross-linkers; tripolyphosphate (TPP), dextran sulphate (DS) and poly-D-glutamic acid (PGA) were used to prepare siRNA loaded CS-TPP/DS/PGA nanoparticles by ionic gelation method. The resulting nanoparticles were compared with regard to their physicochemical properties including particle size, zeta potential, morphology, binding and encapsulation efficiencies. Among all the formulations prepared with different cross linkers, CS-TPP-siRNA had the smallest particle size (ranged from 127 ± 9.7 to 455 ± 12.9 nm) with zeta potential ranged from +25.1 ± 1.5 to +39.4 ± 0.5 mV, and high entrapment (>95%) and binding efficiencies. Similarly, CS-TPP nanoparticles showed better siRNA protection during storage at 4˚C and as determined by serum protection assay. TEM micrographs revealed the assorted morphology of CS-TPP-siRNA nanoparticles in contrast to irregular morphology displayed by CS-DS-siRNA and CS-PGA-siRNA nanoparticles. All siRNA loaded CS-TPP/DS/PGA nanoparticles showed initial burst release followed by sustained release of siRNA. Moreover, all the formulations showed low and concentration-dependent cytotoxicity with human colorectal cancer cells (DLD-1), in vitro. The cellular uptake studies with CS-TPP-siRNA nanoparticles showed successful delivery of siRNA within cytoplasm of DLD-1 cells. The results demonstrate that ionically cross-linked CS-TPP nanoparticles are biocompatible non-viral gene delivery system and generate a solid ground for further optimization studies, for example with regard to steric stabilization and targeting. PMID:26068222

  1. Simultaneous spectroscopic measurements of the interior temperature and induced cargo release from pore-restricted mesoporous silica nanoparticles

    NASA Astrophysics Data System (ADS)

    Dong, Juyao; Zink, Jeffrey I.

    2016-05-01

    Temperature changes initiated within nano structures are being increasingly used to externally activate responsive delivery vehicles. Yet, the precise measurement of the nano environment temperature increase and its correlation with the induced macroscopic cargo release are difficult to achieve. In this study, we focus on a photothermally activated drug delivery system based on mesoporous silica nanoparticles, and use an optical nanothermometer - NaYF4:Yb3+,Er3+ crystals - for a ratiometric temperature measurement. Using fluorescent dyes as the payload molecule, both the nanoparticle interior temperature change and the macroscopic cargo release amount are monitored simultaneously by fluorescent spectroscopy. We found that the cargo release lags the temperature increase by about 5 min, revealing the threshold temperature that the particles have to reach before a substantial release could happen. Using this spectroscopic method, we are able to directly compare and correlate a nano environment event with its stimulated macroscopic results.Temperature changes initiated within nano structures are being increasingly used to externally activate responsive delivery vehicles. Yet, the precise measurement of the nano environment temperature increase and its correlation with the induced macroscopic cargo release are difficult to achieve. In this study, we focus on a photothermally activated drug delivery system based on mesoporous silica nanoparticles, and use an optical nanothermometer - NaYF4:Yb3+,Er3+ crystals - for a ratiometric temperature measurement. Using fluorescent dyes as the payload molecule, both the nanoparticle interior temperature change and the macroscopic cargo release amount are monitored simultaneously by fluorescent spectroscopy. We found that the cargo release lags the temperature increase by about 5 min, revealing the threshold temperature that the particles have to reach before a substantial release could happen. Using this spectroscopic method, we are

  2. Influence of polymerization technique and experimental variables on the particle properties and release kinetics of methotrexate from poly(butylcyanoacrylate) nanoparticles.

    PubMed

    Reddy, Lakkireddy Harivardhan; Murthy, Rayasa Ramachandra

    2004-06-01

    Poly(butylcyanoacrylate) nanoparticles were prepared by dispersion polymerization (DP) and emulsion polymerization (EP) of n-butyl cyanoacrylate monomer. The particles were characterized by infrared spectroscopy, differential scanning calorimetry, X-ray diffractometry and transmission electron microscopy. Particle properties such as size and zeta potential were determined for nanoparticles prepared by DP and EP techniques and compared. EP technique resulted in a low particle size compared to the DP. A high zeta potential was observed for nanoparticles prepared by the DP method. Incorporation of methotrexate resulted in a decrease in zeta potential in both types of nanoparticles, the decrease being greater in DP nanoparticles. Effect of experimental variables such as monomer concentration, polymerization time and temperature on drug entrapment and particle size was studied. Both types of nanoparticles showed an increase in drug entrapment with increased monomer concentrations. Variable polymerization time did not influence the drug entrapment of EP nanoparticles. Polymerization at 60 +/- 2 degrees C resulted in a decrease of drug entrapment and a great increase in the particle size of both types of nanoparticles. In vitro drug release studies showed a comparatively high release of methotrexate from DP nanoparticles suggesting the channelizing effect of dextran chains incorporated into nanoparticles during polymerization. Though the release profiles of nanoparticles appeared similar, a significant difference in release rates was found for DP and EP nanoparticles in 0.1 mol L(-1) HCl and pH 7.4 phosphate buffer (p < 0.01). Drug release data indicate that the release of methotrexate from DP and EP nanoparticles followed Fickian diffusion in 0.1 mol L(-1) HCl, while the mechanism was found anomalous in pH 7.4 phosphate buffer. An effort was also made to critically correlate the properties of nanoparticles synthesized by the above two techniques, and emphasize the

  3. Tailorable Release of Small Molecules Utilizing Plant Viral Nanoparticles and Fibrous Matrix

    NASA Astrophysics Data System (ADS)

    Cao, Jing

    We have engineered Red clover necrotic mosaic virus (RCNMV) derived plant viral nanoparticles (PVNs) within a fibrous matrix to optimize its application for delivery and controlled release of active ingredients. RCNMV's structure and unique response to divalent cation depletion and re-addition enables the infusion of small molecules into its viral capsid through a pore formation mechanism. While this PVN technology shows a potential use in nano-scale therapeutic drug delivery, its inherent molecular dynamics to environmental stimuli places a constraint on its application and functionality as a vehicle for tailorable release of loading cargo. In this study, we enhance the understanding of the PVN technology by elucidating its mechanism for loading and triggered release of doxorubicin (Dox), a chemotherapeutic drug for breast cancer. Of critical importance is the methodology for manipulation of Dox's loading capacity and its binding location on either the exterior or interior of the virion capsid. The ability to control the active ingredient binding location provides an additional approach of tunable release from the PVN delivery vehicle besides its inherent pH- and ion- responsive release of loading cargo. The efficacious and controlled release strategy for agricultural active ingredients, such as nematicides, is also a large social need right now. Crop infestation of plant parasite nematodes causes in excess of 157 billion in worldwide crop damage annually. If an effective control strategy for these pests could be developed, it is estimated that the current market for effective nematicides is between 700 million and $1 billion each year worldwide. In this study, we report on the utilization of PVN technology to encapsulate the biological nematicide, abamectin (Abm), within the PVN's interior capsid (PVNAbm). Creating PVNAbm addresses Abm's issues of soil immobility while rendering a controlled release strategy for its bioavailability to root knot nematodes (RKNs

  4. Release and bioactivity of PACA nanoparticles containing D-Lys⁶-GnRH for brushtail possum fertility control.

    PubMed

    Kafka, Alexandra P; McLeod, Bernie J; Rades, Thomas; McDowell, Arlene

    2011-02-10

    Poly(ethylcyanoacrylate) (PECA) nanoparticles containing the chemical sterilitant D-Lys⁶-GnRH were prepared by an in situ interfacial polymerization technique. Their potential as a peroral delivery system for biocontrol of the brushtail possum, a major pest species in New Zealand, was evaluated. Peptide release from resulting particles was studied in vitro in artificial gastric juice (AGJ), simulated intestinal fluids (SIF) and brushtail possum plasma. The nanoparticles released a small fraction of bioactive over 6h in AGJ and SIF (<5%), while staying intact and retaining fractions of intact D-Lys⁶-GnRH. In contrast, 60% of D-Lys⁶-GnRH was released after 1h in possum plasma. The nanoparticles were also administered in vivo into the caecum of brushtail possums. A significant biological response, measured as an increase in plasma luteinizing hormone (LH), was evident 10 min after administration. This demonstrates not only that PECA nanoparticles were able to facilitate the uptake of D-Lys⁶-GnRH from the caecum into systemic circulation but also that sufficient bioactive peptide reached the pituitary to exert a significant LH response following GnRH receptor mediated endocytosis. Hence, it can be concluded that PECA nanoparticles comprise a promising formulation strategy for the peroral delivery of the chemical sterilitant D-Lys⁶-GnRH to the brushtail possum in New Zealand.

  5. Comparison of drug release from liquid crystalline monoolein dispersions and solid lipid nanoparticles using a flow cytometric technique

    PubMed Central

    Dawoud, Mohamed Z.; Nasr, Mohamed

    2016-01-01

    Colloidal lipid particles such as solid lipid nanoparticles and liquid crystalline nanoparticles have great opportunities as drug carriers especially for lipophilic drugs intended for intravenous administration. In order to evaluate drug release from these nanoparticles and determine their behavior after administration, emulsion droplets were used as a lipophilic compartment to which the transfer of a model drug was measured. The detection of the model drug transferred from monoolein cubic particles and trimyristin solid lipid nanoparticles into emulsion droplets was performed using a flow cytometric technique. A higher rate and amount of porphyrin transfer from the solid lipid nanoparticles compared to the monoolein cubic particles was observed. This difference might be attributed to the formation of a highly ordered particle which leads to the expulsion of drug to the surface of the crystalline particle. Furthermore, the sponge-like structure of the monoolein cubic particles decreases the rate and amount of drug transferred. In conclusion, the flow cytometric technique is a suitable technique to study drug transfer from these carriers to large lipophilic acceptors. Monoolein cubic particles with their unique structure can be used successfully as a drug carrier with slow drug release compared with trimyristin nanoparticles. PMID:27006901

  6. Mesoporous Silica Nanoparticles as Controlled Release Drug Delivery and Gene Transfection Carriers

    SciTech Connect

    Igor I. Slowing; Juan L. Viveo-Escoto; Chia-Wen Wu; Victor S. Y. Lin

    2008-04-10

    In this review, we highlight the recent research developments of a series of surface-functionalized mesoporous silica nanoparticle (MSN) materials as efficient drug delivery carriers. The synthesis of this type of MSN materials is described along with the current methods for controlling the structural properties and chemical functionalization for biotechnological and biomedical applications. We summarized the advantages of using MSN for several drug delivery applications. The recent investigations of the biocompatibility of MSN in vitro are discussed. We also describe the exciting progress on using MSN to penetrate various cell membranes in animal and plant cells. The novel concept of gatekeeping is introduced and applied to the design of a variety of stimuli-responsive nanodevices. We envision that these MSN-based systems have a great potential for a variety of drug delivery applications, such as the site-specific delivery and intracellular controlled release of drugs, genes, and other therapeutic agents.

  7. Destruction of Opportunistic Pathogens via Polymer Nanoparticle-Mediated Release of Plant-Based Antimicrobial Payloads.

    PubMed

    Amato, Dahlia N; Amato, Douglas V; Mavrodi, Olga V; Braasch, Dwaine A; Walley, Susan E; Douglas, Jessica R; Mavrodi, Dmitri V; Patton, Derek L

    2016-05-01

    The synthesis of antimicrobial thymol/carvacrol-loaded polythioether nanoparticles (NPs) via a one-pot, solvent-free miniemulsion thiol-ene photopolymerization process is reported. The active antimicrobial agents, thymol and carvacrol, are employed as "solvents" for the thiol-ene monomer phase in the miniemulsion to enable facile high capacity loading (≈50% w/w), excellent encapsulation efficiencies (>95%), and elimination of all postpolymerization purification processes. The NPs serve as high capacity reservoirs for slow-release and delivery of thymol/carvacrol-combination payloads that exhibit inhibitory and bactericidal activity (>99.9% kill efficiency at 24 h) against gram-positive and gram-negative bacteria, including both saprophytic (Bacillus subtilis ATCC 6633 and Escherichia coli ATCC 25922) and pathogenic species (E. coli ATCC 43895, Staphylococcus aureus RN6390, and Burkholderia cenocepacia K56-2). This report is among the first to demonstrate antimicrobial efficacy of essential oil-loaded nanoparticles against B. cenocepacia - an innately resistant opportunistic pathogen commonly associated with debilitating respiratory infections in cystic fibrosis. Although a model platform, these results point to promising pathways to particle-based delivery of plant-derived extracts for a range of antimicrobial applications, including active packaging materials, topical antiseptics, and innovative therapeutics. PMID:26946055

  8. Water soluble nanoporous nanoparticle for in vivo targeted drug delivery and controlled release in B cells tumor context

    NASA Astrophysics Data System (ADS)

    de Angelis, F.; Pujia, A.; Falcone, C.; Iaccino, E.; Palmieri, C.; Liberale, C.; Mecarini, F.; Candeloro, P.; Luberto, L.; de Laurentiis, A.; Das, G.; Scala, G.; di Fabrizio, E.

    2010-10-01

    Multitasking nanoparticles are gaining great attention for smart drug delivery systems. The exploration of the nano-scale opens new concrete opportunities for revealing new properties and undiscovered cell-particle interactions. Here we present a biodegradable nanoporous silicon nanoparticle that can be successfully employed for in vivo targeted drug delivery and sustained release. The bare nanoporous nanocarriers can be accurately designed and fabricated with an effective control of porosity, surface chemistry and particle size, up to a few nm. The proposed nanoparticles exhibit several remarkable features including high payload, biodegradability, no toxicity, and multiple loading in water without the need of additional chemical reagents at room temperature. The targeting strategy is based on phage display technology that was successfully used to discover cell surface binding peptide for murine B lymphoma A20 cell line. The peptide used in combination with the nanoporous nanoparticles allows an efficient in vivo targeting, a sustained release and a sensible therapeutic effect.Multitasking nanoparticles are gaining great attention for smart drug delivery systems. The exploration of the nano-scale opens new concrete opportunities for revealing new properties and undiscovered cell-particle interactions. Here we present a biodegradable nanoporous silicon nanoparticle that can be successfully employed for in vivo targeted drug delivery and sustained release. The bare nanoporous nanocarriers can be accurately designed and fabricated with an effective control of porosity, surface chemistry and particle size, up to a few nm. The proposed nanoparticles exhibit several remarkable features including high payload, biodegradability, no toxicity, and multiple loading in water without the need of additional chemical reagents at room temperature. The targeting strategy is based on phage display technology that was successfully used to discover cell surface binding peptide for

  9. Magnetic NGF-releasing PLLA/iron oxide nanoparticles direct extending neurites and preferentially guide neurites along aligned electrospun microfibers.

    PubMed

    Zuidema, Jonathan M; Provenza, Christina; Caliendo, Tyler; Dutz, Silvio; Gilbert, Ryan J

    2015-11-18

    Nerve growth factor releasing composite nanoparticles (NGF-cNPs) were developed to direct the extension of neurite outgrowth from dorsal root ganglia (DRG). Iron oxide magnetic nanoparticles were incorporated into poly-l-lactic acid (PLLA) nanoparticles in order to position the NGF-cNPs in a culture dish. Neurites growing from DRG extended toward the NGF released from the NGF-cNPs. DRG were then cultured on aligned PLLA microfibers in the presence of NGF-cNPs, and these biomaterials combined to align DRG neurite extension along one axis and preferentially toward the NGF-cNPs. This combinatorial biomaterial approach shows promise as a strategy to direct the extension of regenerating neurites. PMID:26322376

  10. Multifunction hexagonal liquid-crystal containing modified surface TiO2 nanoparticles and terpinen-4-ol for controlled release

    PubMed Central

    Manaia, Eloísa Berbel; Kaminski, Renata Cristina Kiatkoski; de Oliveira, Anselmo Gomes; Corrêa, Marcos Antonio; Chiavacci, Leila Aparecida

    2015-01-01

    Multifunctional products have been developed to combine the benefits of functional components and terpinen-4-ol (TP) delivery systems. In this way, p-toluene sulfonic acid modified titanium dioxide (TiO2) nanoparticles and TP, an antioxidant, have been incorporated in liquid-crystalline formulations for photoprotection and controlled release of the TP, respectively. By X-ray powder diffraction and diffuse reflectance spectroscopy, we noted that using p-toluene sulfonic acid as a surface modifier made it possible to obtain smaller and more transparent TiO2 nanoparticles than those commercially available. The liquid-crystalline formulation containing the inorganic ultraviolet filter was classified as broad-spectrum performance by the absorbance spectroscopy measurements. The formulations containing modified TiO2 nanoparticles and TP were determined to be in the hexagonal phase by polarized light microscopy and small-angle X-ray scattering, which makes possible the controlled released of TP following zero-order kinetics. The developed formulations can control the release of TP. Constant concentrations of the substance have been released per time unit, and the modified TiO2 nanoparticles can act as a transparent inorganic sunscreen. PMID:25653523

  11. N,O6-partially acetylated chitosan nanoparticles hydrophobically-modified for controlled release of steroids and vitamin E.

    PubMed

    Quiñones, Javier Pérez; Gothelf, Kurt Vesterager; Kjems, Jørgen; Caballero, Ángeles María Heras; Schmidt, Claudia; Covas, Carlos Peniche

    2013-01-01

    Diosgenin, two synthetic analogs of brassinosteroids, testosterone and dl-α-tocopherol were covalently linked to synthetic water-soluble N,O6-partially acetylated chitosan, for their controlled release. Drug linking was confirmed by FTIR spectroscopy and proton NMR. Conjugates were also characterized by differential scanning calorimetry and wide-angle X-ray diffraction. These conjugates formed self-assembled nanoparticles in aqueous solution with particle sizes ranging from 197 to 358 nm and drug contents between 11.8 and 56.4% (w/w). Spherical 30-60 nm nanoparticles were observed by scanning electron microscopy and transmission electron microscopy upon drying. In vitro release studies performed at acid pH indicated a drug release dependence on substitution degree and particle sizes. Almost constant release rates were observed during the first 6-8h. Brassinosteroids-modified nanoparticles showed good agrochemical activity in radish seeds bioassay at 10(-1) to 10(-4) mg mL(-1). Tocopheryl-modified nanoparticles exhibited radical scavenging activity in DPPH test. PMID:23044115

  12. Remote-Controlled DNA Release from Fe3O4@Au Nanoparticles Using an Alternating Electromagnetic Field.

    PubMed

    Liu, Min; Wang, Zhuyuan; Zong, Shenfei; Chen, Hui; Zhu, Dan; Zhong, Yuan; Cui, Yiping

    2015-06-01

    We demonstrated a remote-controlled DNA release strategy, in which irradiation of nanoparticles with an alternating electromagnetic field (AMF) results in DNA release on demand. The method we developed used 6-carboxyfluorescein (FAM)-labeled diblock DNA to modify Fe3O4@Au nanoparticles (NPs) through the affinity of adenine with the surfaces of the NPs. The DNA release was confirmed by zeta potential measurement, surface-enhanced Raman scattering spectroscopy, gel electrophoresis, and fluorescence spectroscopy. The experimental results showed that the DNA was released into the surrounding medium under irradiation with an AMF at a frequency of 20-25 kHz. The DNA release was efficient (60%-70%), and externally controllable by tuning various parameters, such as the sequences length of the diblock DNA, the pH value of environmental solutions, and the power and the time of AMF irradiation. Furthermore, the AMF-triggered DNA release was successfully performed in human cervical cancer (HeLa) cells, demonstrating the system's ability to maintain the release behavior in vitro. This remote-controlled DNA release method presents a new application for DNA-modified NPs in targeted therapies. PMID:26353587

  13. Remote-Controlled DNA Release from Fe3O4@Au Nanoparticles Using an Alternating Electromagnetic Field.

    PubMed

    Liu, Min; Wang, Zhuyuan; Zong, Shenfei; Chen, Hui; Zhu, Dan; Zhong, Yuan; Cui, Yiping

    2015-06-01

    We demonstrated a remote-controlled DNA release strategy, in which irradiation of nanoparticles with an alternating electromagnetic field (AMF) results in DNA release on demand. The method we developed used 6-carboxyfluorescein (FAM)-labeled diblock DNA to modify Fe3O4@Au nanoparticles (NPs) through the affinity of adenine with the surfaces of the NPs. The DNA release was confirmed by zeta potential measurement, surface-enhanced Raman scattering spectroscopy, gel electrophoresis, and fluorescence spectroscopy. The experimental results showed that the DNA was released into the surrounding medium under irradiation with an AMF at a frequency of 20-25 kHz. The DNA release was efficient (60%-70%), and externally controllable by tuning various parameters, such as the sequences length of the diblock DNA, the pH value of environmental solutions, and the power and the time of AMF irradiation. Furthermore, the AMF-triggered DNA release was successfully performed in human cervical cancer (HeLa) cells, demonstrating the system's ability to maintain the release behavior in vitro. This remote-controlled DNA release method presents a new application for DNA-modified NPs in targeted therapies.

  14. Preparation of starch nanoparticles in a water-in-ionic liquid microemulsion system and their drug loading and releasing properties.

    PubMed

    Zhou, Gang; Luo, Zhigang; Fu, Xiong

    2014-08-13

    An ionic liquid microemulsion consisting of 1-butyl-3-methylimidazolium hexafluorophosphate ([Bmim]PF₆), surfactant TX-100, 1-butanol, and water was prepared. The water-in-[Bmim]PF₆ (W/IL), bicontinuous, and [Bmim]PF₆-in-water (IL/W) microregions of the microemulsion were identified by conductivity measurements. Starch nanoparticles with a mean diameter of 91.4 nm were synthesized with epichlorohydrin as cross-linker through W/IL microemulsion cross-linking reaction at 50 °C for 4 h. Fourier transform infrared spectroscopy (FTIR) data demonstrated the formation of cross-linking bonds in starch molecules. Scanning electron microscopy (SEM) revealed that starch nanoparticles were spherical and that some particles showed aggregation formation. Furthermore, drug loading and releasing properties of starch nanoparticles were investigated with mitoxantrone hydrochloride as a drug model. This work provides an efficient and environmentally friendly approach for the preparation of starch nanoparticles, which is beneficial to their further application. PMID:25069988

  15. The spherical nanoparticle-encapsulated chlorhexidine enhances anti-biofilm efficiency through an effective releasing mode and close microbial interactions.

    PubMed

    Li, Xuan; Wong, Chi-Hin; Ng, Tsz-Wing; Zhang, Cheng-Fei; Leung, Ken Cham-Fai; Jin, Lijian

    2016-01-01

    We reported two forms (sphere and wire) of newly fabricated chlorhexidine (CHX)-loaded mesoporous silica nanoparticles (MSNs), and investigated their releasing capacities and anti-biofilm efficiencies. The interactions of the blank MSNs with planktonic oral microorganisms were assessed by field emission scanning electron microscopy. The anti-biofilm effects of the two forms of nanoparticle-encapsulated CHX were examined by 2,3-bis (2-methoxy- 4-nitro-5-sulfo-phenyl)-2H-tetrazolium-5-carboxanilide. The profiles of biofilm penetration were analyzed by fluorescent-labeled MSNs using confocal microscopy and ImageJ. The spherical MSNs with an average diameter of 265 nm exhibited a larger surface area and faster CHX-releasing rate than the MSN wires. The field emission scanning electron microscopy images showed that both shaped MSNs enabled to attach and further fuse with the surfaces of testing microbes. Meanwhile, the nanoparticle-encapsulated CHX could enhance the anti-biofilm efficiency with reference to its free form. Notably, the spherical nanoparticle-encapsulated CHX presented with a greater anti-biofilm capacity than the wire nanoparticle-encapsulated CHX, partly due to their difference in physical property. Furthermore, the relatively even distribution and homogeneous dispersion of spherical MSNs observed in confocal images may account for the enhanced penetration of spherical nanoparticle-encapsulated CHX into the microbial biofilms and resultant anti-biofilm effects. These findings reveal that the spherical nanoparticle-encapsulated CHX could preferably enhance its anti-biofilm efficiency through an effective releasing mode and close interactions with microbes. PMID:27330290

  16. The spherical nanoparticle-encapsulated chlorhexidine enhances anti-biofilm efficiency through an effective releasing mode and close microbial interactions

    PubMed Central

    Li, Xuan; Wong, Chi-Hin; Ng, Tsz-Wing; Zhang, Cheng-Fei; Leung, Ken Cham-Fai; Jin, Lijian

    2016-01-01

    We reported two forms (sphere and wire) of newly fabricated chlorhexidine (CHX)-loaded mesoporous silica nanoparticles (MSNs), and investigated their releasing capacities and anti-biofilm efficiencies. The interactions of the blank MSNs with planktonic oral microorganisms were assessed by field emission scanning electron microscopy. The anti-biofilm effects of the two forms of nanoparticle-encapsulated CHX were examined by 2,3-bis (2-methoxy- 4-nitro-5-sulfo-phenyl)-2H-tetrazolium-5-carboxanilide. The profiles of biofilm penetration were analyzed by fluorescent-labeled MSNs using confocal microscopy and ImageJ. The spherical MSNs with an average diameter of 265 nm exhibited a larger surface area and faster CHX-releasing rate than the MSN wires. The field emission scanning electron microscopy images showed that both shaped MSNs enabled to attach and further fuse with the surfaces of testing microbes. Meanwhile, the nanoparticle-encapsulated CHX could enhance the anti-biofilm efficiency with reference to its free form. Notably, the spherical nanoparticle-encapsulated CHX presented with a greater anti-biofilm capacity than the wire nanoparticle-encapsulated CHX, partly due to their difference in physical property. Furthermore, the relatively even distribution and homogeneous dispersion of spherical MSNs observed in confocal images may account for the enhanced penetration of spherical nanoparticle-encapsulated CHX into the microbial biofilms and resultant anti-biofilm effects. These findings reveal that the spherical nanoparticle-encapsulated CHX could preferably enhance its anti-biofilm efficiency through an effective releasing mode and close interactions with microbes. PMID:27330290

  17. Optimization of synthesis process of thermally-responsive poly-n-isopropylacrylamide nanoparticles for controlled release of antimicrobial hydrophobic compounds

    NASA Astrophysics Data System (ADS)

    Hill, Laura E.; Gomes, Carmen L.

    2014-12-01

    The goal of this study was to develop an effective method to synthesize poly-n-isopropylacrylamide (PNIPAAM) nanoparticles with entrapped cinnamon bark extract (CBE) to improve its delivery to foodborne pathogens and control its release with temperature stimuli. CBE was used as a model for hydrophobic natural antimicrobials. A top-down procedure using crosslinked PNIPAAM was compared to a bottom-up procedure using NIPAAM monomer. Both processes relied on self-assembly of the molecules into micelles around the CBE at 40 °C. Processing conditions were compared including homogenization time of the polymer, hydration time prior to homogenization, lyophilization, and the effect of particle ultrafiltration. The top-down versus bottom-up synthesis methods yielded particles with significantly different characteristics, especially their release profiles and antimicrobial activities. The synthesis methods affected particle size, with the bottom-up procedure resulting in smaller (P < 0.05) diameters than the top-down procedure. The controlled release profile of CBE from nanoparticles was dependent on the release media temperature. A faster, burst release was observed at 40 °C and a slower, more sustained release was observed at lower temperatures. PNIPAAM particles containing CBE were analyzed for their antimicrobial activity against Salmonella enterica serovar Typhimurium LT2 and Listeria monocytogenes Scott A. The PNIPAAM particles synthesized via the top-down procedure had a much faster release, which led to a greater (P < 0.05) antimicrobial activity. Both of the top-down nanoparticles performed similarly, therefore the 7 min homogenization time nanoparticles would be the best for this application, as the process time is shorter and little improvement was seen by using a slightly longer homogenization.

  18. Antibacterial activity and ion release of bonding agent containing amorphous calcium phosphate nanoparticles

    PubMed Central

    Chen, Chen; Weir, Michael D.; Cheng, Lei; Lin, Nancy; Lin-Gibson, Sheng; Chow, Laurence C.; Zhou, Xuedong; Xu, Hockin H. K.

    2015-01-01

    Objectives Recurrent caries at the margins is a primary reason for restoration failure. The objectives of this study were to develop bonding agent with the double benefits of antibacterial and remineralizing capabilities, to investigate the effects of NACP filler level and solution pH on Ca and P ion release from adhesive, and to examine the antibacterial and dentin bond properties. Methods Nanoparticles of amorphous calcium phosphate (NACP) and a quaternary ammonium monomer (dimethylaminododecyl methacrylate, DMADDM) were synthesized. Scotchbond Multi-Purpose (SBMP) primer and adhesive served as control. DMADDM was incorporated into primer and adhesive at 5% by mass. NACP was incorporated into adhesive at filler mass fractions of 10%, 20%, 30% and 40%. A dental plaque microcosm biofilm model was used to test the antibacterial bonding agents. Calcium (Ca) and phosphate (P) ion releases from the cured adhesive samples were measured vs. filler level and solution pH of 7, 5.5 and 4. Results Adding 5% DMADDM and 10–40% NACP into bonding agent, and water-aging for 28 days, did not affect dentin bond strength, compared to SBMP control at 1 day (p > 0.1). Adding DMADDM into bonding agent substantially decreased the biofilm metabolic activity and lactic acid production. Total microorganisms, total streptococci, and mutans streptococci were greatly reduced for bonding agents containing DMADDM. Increasing NACP filler level from 10% to 40% in adhesive increased the Ca and P ion release by an order of magnitude. Decreasing solution pH from 7 to 4 increased the ion release from adhesive by 6–10 folds. Significance Bonding agents containing antibacterial DMADDM and remineralizer NACP were formulated to have Ca and P ion release, which increased with NACP filler level from 10% to 40% in adhesive. NACP adhesive was “smart” and dramatically increased the ion release at cariogenic pH 4, when these ions would be most-needed to inhibit caries. Therefore, bonding agent

  19. Solid and liquid lipid-based binary solid lipid nanoparticles of diacerein: in vitro evaluation of sustained release, simultaneous loading of gold nanoparticles, and potential thermoresponsive behavior

    PubMed Central

    Rehman, Mubashar; Madni, Asadullah; Ihsan, Ayesha; Khan, Waheed Samraiz; Khan, Muhammad Imran; Mahmood, Muhammad Ahmad; Ashfaq, Muhammad; Bajwa, Sadia Zafar; Shakir, Imran

    2015-01-01

    Binary fatty acid mixture-based solid lipid nanoparticles (SLNs) were prepared for delivery of diacerein, a novel disease-modifying osteoarthritis drug, with and without simultaneously loaded gold nanoparticles (GNPs). In order to optimize SLNs for temperature-responsive release, lipid mixtures were prepared using different ratios of solid (stearic acid or lauric acid) and liquid (oleic acid) fatty acids. SLNs were prepared by microemulsification (53 nm), hot melt encapsulation (10.4 nm), and a solvent emulsification-evaporation technique (7.8 nm). The physicochemical characteristics of SLNs were studied by Zetasizer, Fourier transform infrared, and X-ray diffraction analysis. High encapsulation of diacerein was achieved with diacerein-loaded and simultaneously GNP-diacerein-loaded SLNs. In vitro dissolution studies revealed a sustained release pattern for diacerein over 72 hours for diacerein-loaded SLNs and 12 hours for GNP-diacerein-loaded SLNs. An increase in diacerein payload increased the release time of diacerein while GNPs decreased it. In addition, rapid release of diacerein over 4 hours was observed at 40°C (melting point of optimized fatty acid mixture), demonstrating that these binary SLNs could be used for thermoresponsive drug delivery. Kinetic modeling indicated that drug release followed zero order and Higuchi diffusion models (R10>0.9), while the Korsmeyer-Peppas model predicted a diffusion release mechanism (n<0.5). PMID:25897224

  20. Solid and liquid lipid-based binary solid lipid nanoparticles of diacerein: in vitro evaluation of sustained release, simultaneous loading of gold nanoparticles, and potential thermoresponsive behavior.

    PubMed

    Rehman, Mubashar; Madni, Asadullah; Ihsan, Ayesha; Khan, Waheed Samraiz; Khan, Muhammad Imran; Mahmood, Muhammad Ahmad; Ashfaq, Muhammad; Bajwa, Sadia Zafar; Shakir, Imran

    2015-01-01

    Binary fatty acid mixture-based solid lipid nanoparticles (SLNs) were prepared for delivery of diacerein, a novel disease-modifying osteoarthritis drug, with and without simultaneously loaded gold nanoparticles (GNPs). In order to optimize SLNs for temperature-responsive release, lipid mixtures were prepared using different ratios of solid (stearic acid or lauric acid) and liquid (oleic acid) fatty acids. SLNs were prepared by microemulsification (53 nm), hot melt encapsulation (10.4 nm), and a solvent emulsification-evaporation technique (7.8 nm). The physicochemical characteristics of SLNs were studied by Zetasizer, Fourier transform infrared, and X-ray diffraction analysis. High encapsulation of diacerein was achieved with diacerein-loaded and simultaneously GNP-diacerein-loaded SLNs. In vitro dissolution studies revealed a sustained release pattern for diacerein over 72 hours for diacerein-loaded SLNs and 12 hours for GNP-diacerein-loaded SLNs. An increase in diacerein payload increased the release time of diacerein while GNPs decreased it. In addition, rapid release of diacerein over 4 hours was observed at 40°C (melting point of optimized fatty acid mixture), demonstrating that these binary SLNs could be used for thermoresponsive drug delivery. Kinetic modeling indicated that drug release followed zero order and Higuchi diffusion models (R(2)>0.9), while the Korsmeyer-Peppas model predicted a diffusion release mechanism (n<0.5).

  1. Enhanced Oral Bioavailability of Efavirenz by Solid Lipid Nanoparticles: In Vitro Drug Release and Pharmacokinetics Studies

    PubMed Central

    Gaur, Praveen Kumar; Mishra, Shikha; Bajpai, Meenakshi; Mishra, Anushika

    2014-01-01

    Solid lipid nanoparticle is an efficient lipid based drug delivery system which can enhance the bioavailability of poorly water soluble drugs. Efavirenz is a highly lipophilic drug from nonnucleoside inhibitor category for treatment of HIV. Present work illustrates development of an SLN formulation for Efavirenz with increased bioavailability. At first, suitable lipid component and surfactant were chosen. SLNs were prepared and analyzed for physical parameters, stability, and pharmacokinetic profile. Efavirenz loaded SLNs were formulated using Glyceryl monostearate as main lipid and Tween 80 as surfactant. ESLN-3 has shown mean particle size of 124.5 ± 3.2 nm with a PDI value of 0.234, negative zeta potential, and 86% drug entrapment. In vitro drug release study has shown 60.6–98.22% drug release in 24 h by various SLN formulations. Optimized SLNs have shown good stability at 40°C ± 2°C and 75 ± 5% relative humidity (RH) for 180 days. ESLN-3 exhibited 5.32-fold increase in peak plasma concentration (Cmax⁡) and 10.98-fold increase in AUC in comparison to Efavirenz suspension (ES). PMID:24967360

  2. Characterization of lysosome-destabilizing DOPE/PLGA nanoparticles designed for cytoplasmic drug release.

    PubMed

    Chhabra, Resham; Grabrucker, Andreas M; Veratti, Patrizia; Belletti, Daniela; Boeckers, Tobias M; Vandelli, Maria Angela; Forni, Flavio; Tosi, Giovanni; Ruozi, Barbara

    2014-08-25

    Polymeric nanoparticles (NPs) offer a promising approach for therapeutic intracellular delivery of proteins, conventionally hampered by short half-lives, instability and immunogenicity. Remarkably, NPs uptake occurs via endocytic internalization leading to NPs content's release within lysosomes. To overcome lysosomal degradation and achieve NPs and/or loaded proteins release into cytosol, we propose the formulation of hybrid NPs by adding 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) as pH sensitive component in the formulation of poly-lactide-co-glycolide (PLGA) NPs. Hybrid NPs, featured by different DOPE/PLGA ratios, were characterized in terms of structure, stability and lipid organization within the polymeric matrix. Experiments on NIH cells and rat primary neuronal cultures highlighted the safety profile of hybrid NPs. Moreover, after internalization, NPs are able to transiently destabilize the integrity of lysosomes in which they are taken up, speeding their escape and favoring cytoplasmatic localization. Thus, these DOPE/PLGA-NPs configure themselves as promising carriers for intracellular protein delivery.

  3. Polyacrylic acid modified upconversion nanoparticles for simultaneous pH-triggered drug delivery and release imaging.

    PubMed

    Jia, Xuekun; Yin, Jinjin; He, Dinggeng; He, Xiaoxiao; Wang, Kemin; Chen, Mian; Li, Yuhong

    2013-12-01

    A poly(acrylicacid)-modified NaYF4:Yb, Er upconversion nanoparticles (PAA-UCNPs) with dual functions of drug delivery and release imaging have been successfully developed. The PAA polymer coated on the surface of UCNPs serve as a pH-sensitive nanovalve for loading drug molecules via electrostatic interaction. The drug-loading efficiency of the PAA-UCNPs was investigated by using doxorubicin hydrochloride (DOX) as a model anticancer drug to evaluate their potential as a delivery system. Results showed loading and releasing of DOX from PAA-UCNPs were controlled by varying pH, with high encapsulation rate at weak alkaline conditions and an increased drug dissociation rate in acidic environment, which is favorable for construct a pH-responsive controlled drug delivery system. The in vitro cytotoxicity test using HeLa cell line indicated that the DOX loaded PAA-UCNPs (DOX@PAA-UCNPs) were distinctly cytotoxic to HeLa cells, while the PAA-UCNPs were highly biocompatible and suitable to use as drug carriers. Furthermore, the upconversion fluorescence resonance energy transfer (UFRET) imaging through the two-photon laser scanning microscopy (TLSM) revealed the time course of intracellular delivery of DOX from DOX@PAA-UCNPs. Thus, PAA-UCNPs are effective for constructing pH-responsive controlled drug delivery systems for multi-functional cancer therapy and imaging. PMID:24266261

  4. [Preparation and release behaviour of mPEG-PLA α-asarone nanoparticles designed for nasal administration].

    PubMed

    Ju, Feng; Pan, Lin-mei; Guo, Li-wei; Zhu, Hua-xu; Li, Bo; Qu, Na; Yang, Chen

    2015-12-01

    Taking α-asarone as model drug, mono methoxy polyethylene glycol-polylactic acid copolymer (mPEG-PLA) as the drug carrier material to prepare drug-loading nanoparticles by premix membrane emulsification for nasal administration. The prepared nanoparticles were spherical with smooth surface and average particle size of 360 nm. Polydispersity index (PDI) was 0. 030, average drug loading of (11.5 ± 0.045) % (n = 3), and the encapsulation efficiency of (86.34 ± 0.11) % (n = 3). X-ray diffraction and differential scanning calorimetry results showed that, α-asarone existed in mPEG-PLA carrier in amorphous or molecular state, different from simple physical mixture. In the in vitro release test in simulated human nasal cavity, α-asarone apis can be released quickly at close to 94% at 102 h, in line with the first-order kinetics (R² = 0.981 9). mPEG-PLA drug-loading nanoparticles release only 54%, with slow release effect, in line with Riger-Peppas model (R² = 0.967 9, n = 0.630 2), for non-fick diffusion, released by the spread of drugs and skeleton dissolution dual control. This provided the foundation for nasal drug delivery in vivo pharmacokinetic study.

  5. Nitric oxide-releasing poly(lactic-co-glycolic acid)-polyethylenimine nanoparticles for prolonged nitric oxide release, antibacterial efficacy, and in vivo wound healing activity.

    PubMed

    Nurhasni, Hasan; Cao, Jiafu; Choi, Moonjeong; Kim, Il; Lee, Bok Luel; Jung, Yunjin; Yoo, Jin-Wook

    2015-01-01

    Nitric oxide (NO)-releasing nanoparticles (NPs) have emerged as a wound healing enhancer and a novel antibacterial agent that can circumvent antibiotic resistance. However, the NO release from NPs over extended periods of time is still inadequate for clinical application. In this study, we developed NO-releasing poly(lactic-co-glycolic acid)-polyethylenimine (PEI) NPs (NO/PPNPs) composed of poly(lactic-co-glycolic acid) and PEI/diazeniumdiolate (PEI/NONOate) for prolonged NO release, antibacterial efficacy, and wound healing activity. Successful preparation of PEI/NONOate was confirmed by proton nuclear magnetic resonance, Fourier transform infrared spectroscopy, and ultraviolet/visible spectrophotometry. NO/PPNPs were characterized by particle size, surface charge, and NO loading. The NO/PPNPs showed a prolonged NO release profile over 6 days without any burst release. The NO/PPNPs exhibited potent bactericidal efficacy against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa concentration-dependently and showed the ability to bind on the surface of the bacteria. We also found that the NO released from the NO/PPNPs mediates bactericidal efficacy and is not toxic to healthy fibroblast cells. Furthermore, NO/PPNPs accelerated wound healing and epithelialization in a mouse model of a MRSA-infected wound. Therefore, our results suggest that the NO/PPNPs presented in this study could be a suitable approach for treating wounds and various skin infections.

  6. Nitric oxide-releasing poly(lactic-co-glycolic acid)-polyethylenimine nanoparticles for prolonged nitric oxide release, antibacterial efficacy, and in vivo wound healing activity

    PubMed Central

    Nurhasni, Hasan; Cao, Jiafu; Choi, Moonjeong; Kim, Il; Lee, Bok Luel; Jung, Yunjin; Yoo, Jin-Wook

    2015-01-01

    Nitric oxide (NO)-releasing nanoparticles (NPs) have emerged as a wound healing enhancer and a novel antibacterial agent that can circumvent antibiotic resistance. However, the NO release from NPs over extended periods of time is still inadequate for clinical application. In this study, we developed NO-releasing poly(lactic-co-glycolic acid)-polyethylenimine (PEI) NPs (NO/PPNPs) composed of poly(lactic-co-glycolic acid) and PEI/diazeniumdiolate (PEI/NONOate) for prolonged NO release, antibacterial efficacy, and wound healing activity. Successful preparation of PEI/NONOate was confirmed by proton nuclear magnetic resonance, Fourier transform infrared spectroscopy, and ultraviolet/visible spectrophotometry. NO/PPNPs were characterized by particle size, surface charge, and NO loading. The NO/PPNPs showed a prolonged NO release profile over 6 days without any burst release. The NO/PPNPs exhibited potent bactericidal efficacy against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa concentration-dependently and showed the ability to bind on the surface of the bacteria. We also found that the NO released from the NO/PPNPs mediates bactericidal efficacy and is not toxic to healthy fibroblast cells. Furthermore, NO/PPNPs accelerated wound healing and epithelialization in a mouse model of a MRSA-infected wound. Therefore, our results suggest that the NO/PPNPs presented in this study could be a suitable approach for treating wounds and various skin infections. PMID:25960648

  7. Nitric oxide-releasing poly(lactic-co-glycolic acid)-polyethylenimine nanoparticles for prolonged nitric oxide release, antibacterial efficacy, and in vivo wound healing activity.

    PubMed

    Nurhasni, Hasan; Cao, Jiafu; Choi, Moonjeong; Kim, Il; Lee, Bok Luel; Jung, Yunjin; Yoo, Jin-Wook

    2015-01-01

    Nitric oxide (NO)-releasing nanoparticles (NPs) have emerged as a wound healing enhancer and a novel antibacterial agent that can circumvent antibiotic resistance. However, the NO release from NPs over extended periods of time is still inadequate for clinical application. In this study, we developed NO-releasing poly(lactic-co-glycolic acid)-polyethylenimine (PEI) NPs (NO/PPNPs) composed of poly(lactic-co-glycolic acid) and PEI/diazeniumdiolate (PEI/NONOate) for prolonged NO release, antibacterial efficacy, and wound healing activity. Successful preparation of PEI/NONOate was confirmed by proton nuclear magnetic resonance, Fourier transform infrared spectroscopy, and ultraviolet/visible spectrophotometry. NO/PPNPs were characterized by particle size, surface charge, and NO loading. The NO/PPNPs showed a prolonged NO release profile over 6 days without any burst release. The NO/PPNPs exhibited potent bactericidal efficacy against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa concentration-dependently and showed the ability to bind on the surface of the bacteria. We also found that the NO released from the NO/PPNPs mediates bactericidal efficacy and is not toxic to healthy fibroblast cells. Furthermore, NO/PPNPs accelerated wound healing and epithelialization in a mouse model of a MRSA-infected wound. Therefore, our results suggest that the NO/PPNPs presented in this study could be a suitable approach for treating wounds and various skin infections. PMID:25960648

  8. Glutathione- and pH-responsive nonporous silica prodrug nanoparticles for controlled release and cancer therapy

    NASA Astrophysics Data System (ADS)

    Xu, Zhigang; Liu, Shiying; Kang, Yuejun; Wang, Mingfeng

    2015-03-01

    A myriad of drug delivery systems such as liposomes, micelles, polymers and inorganic nanoparticles (NPs) have been developed for cancer therapy. Very few of them, however, have the ability to integrate multiple functionalities such as specific delivery, high circulation stability, controllable release and good biocompatibility and biodegradability in a single system to improve the therapeutic efficacy. Herein, we report two types of stimuli-responsive nonporous silica prodrug NPs towards this goal for controlled release of anticancer drugs and efficient combinatorial cancer therapy. As a proof of concept, anticancer drugs camptothecin (CPT) and doxorubicin (DOX) were covalently encapsulated into silica matrices through glutathione (GSH)-responsive disulfide and pH-responsive hydrazone bonds, respectively, resulting in NPs with sizes tunable in the range of 50-200 nm. Both silica prodrug NPs showed stimuli-responsive controlled release upon exposure to a GSH-rich or acidic environment, resulting in improved anticancer efficacy. Notably, two prodrug NPs simultaneously taken up by HeLa cells showed a remarkable combinatorial efficacy compared to free drug pairs. These results suggest that the stimuli-responsive silica prodrug NPs are promising anticancer drug carriers for efficient cancer therapy.A myriad of drug delivery systems such as liposomes, micelles, polymers and inorganic nanoparticles (NPs) have been developed for cancer therapy. Very few of them, however, have the ability to integrate multiple functionalities such as specific delivery, high circulation stability, controllable release and good biocompatibility and biodegradability in a single system to improve the therapeutic efficacy. Herein, we report two types of stimuli-responsive nonporous silica prodrug NPs towards this goal for controlled release of anticancer drugs and efficient combinatorial cancer therapy. As a proof of concept, anticancer drugs camptothecin (CPT) and doxorubicin (DOX) were

  9. Formation and Biopharmaceutical Characterization of Electrospun PVP Mats with Propolis and Silver Nanoparticles for Fast Releasing Wound Dressing

    PubMed Central

    Adomavičiūtė, Erika; Stanys, Sigitas; Žilius, Modestas; Juškaitė, Vaida; Pavilonis, Alvydas; Briedis, Vitalis

    2016-01-01

    Antibacterial, antiviral, antifungal, antioxidant, anti-inflammatory, and anticancer activities of propolis and its ability to stimulate the immune system and promote wound healing make it a proper component for wound dressing materials. Silver nanoparticles are recognized to demonstrate strong antiseptic and antimicrobial activity; thus, it also could be considered in the development of products for wound healing. Combining propolis and silver nanoparticles can result in improved characteristics of products designed for wound healing and care. The aim of this study was to formulate electrospun fast dissolving mats for wound dressing containing propolis ethanolic extract and silver nanoparticles. Produced electrospun nano/microfiber mats were evaluated studying their structure, dissolution rate, release of propolis phenolic compounds and silver nanoparticles, and antimicrobial activity. Biopharmaceutical characterization of electrospun mats demonstrated fast release of propolis phenolic compounds and silver nanoparticles. Evaluation of antimicrobial activity on Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris, Bacillus subtilis, Bacillus cereus, and Candida albicans strains confirmed the ability of electrospun mats to inhibit the growth of the tested microorganisms. PMID:26981531

  10. Formation and Biopharmaceutical Characterization of Electrospun PVP Mats with Propolis and Silver Nanoparticles for Fast Releasing Wound Dressing.

    PubMed

    Adomavičiūtė, Erika; Stanys, Sigitas; Žilius, Modestas; Juškaitė, Vaida; Pavilonis, Alvydas; Briedis, Vitalis

    2016-01-01

    Antibacterial, antiviral, antifungal, antioxidant, anti-inflammatory, and anticancer activities of propolis and its ability to stimulate the immune system and promote wound healing make it a proper component for wound dressing materials. Silver nanoparticles are recognized to demonstrate strong antiseptic and antimicrobial activity; thus, it also could be considered in the development of products for wound healing. Combining propolis and silver nanoparticles can result in improved characteristics of products designed for wound healing and care. The aim of this study was to formulate electrospun fast dissolving mats for wound dressing containing propolis ethanolic extract and silver nanoparticles. Produced electrospun nano/microfiber mats were evaluated studying their structure, dissolution rate, release of propolis phenolic compounds and silver nanoparticles, and antimicrobial activity. Biopharmaceutical characterization of electrospun mats demonstrated fast release of propolis phenolic compounds and silver nanoparticles. Evaluation of antimicrobial activity on Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris, Bacillus subtilis, Bacillus cereus, and Candida albicans strains confirmed the ability of electrospun mats to inhibit the growth of the tested microorganisms.

  11. Sequential studies of silver released from silver nanoparticles in aqueous media simulating sweat, laundry detergent solutions and surface water.

    PubMed

    Hedberg, Jonas; Skoglund, Sara; Karlsson, Maria-Elisa; Wold, Susanna; Odnevall Wallinder, Inger; Hedberg, Yolanda

    2014-07-01

    From an increased use of silver nanoparticles (Ag NPs) as an antibacterial in consumer products follows a need to assess the environmental interaction and fate of their possible dispersion and release of silver. This study aims to elucidate an exposure scenario of the Ag NPs potentially released from, for example, impregnated clothing by assessing the release of silver and changes in particle properties in sequential contact with synthetic sweat, laundry detergent solutions, and freshwater, simulating a possible transport path through different aquatic media. The release of ionic silver is addressed from a water chemical perspective, compared with important particle and surface characteristics. Released amounts of silver in the sequential exposures were significantly lower, approximately a factor of 2, than the sum of each separate exposure. Particle characteristics such as speciation (both of Ag ionic species and at the Ag NP surface) influenced the release of soluble silver species present on the surface, thereby increasing the total silver release in the separate exposures compared with sequential immersions. The particle stability had no drastic impact on the silver release as most of the Ag NPs were unstable in solution. The silver release was also influenced by a lower pH (increased release of silver), and cotransported zeolites (reduced silver in solution).

  12. Preparation and evaluation of thiomer nanoparticles via high pressure homogenization.

    PubMed

    Hoyer, Herbert; Schlocker, Wolfgang; Greindl, Melanie; Ostermann, Thomas; Bernkop-Schnürch, Andreas

    2010-01-01

    The aim of this study was to establish and evaluate a high pressure homogenization method for the preparation of thiomer nanoparticles. Particles were formulated by incorporation of the model protein horseradish peroxidase in chitosan-glutathione (Ch-GSH) and poly(acrylic acid)-glutathione (PAA-GSH) via co-precipitation followed by air jet milling. The resulting microparticles were suspended in distilled water using an Ultraturax and subsequently micronized by high pressure homogenization. Finally, resulting particles were evaluated regarding size distribution, shape, zeta potential, drug load, protein activity and release behaviour. The mean particle size after 30 cycles with a pressure of 1500 bar was 538 +/- 94 nm for particles consisting of Ch-GSH and 638 +/- 94 nm for particles consisting of PAA-GSH. Nanoparticles of Ch-GSH had a positive zeta-potential of +1.03 mv, whereas nanoparticles from PAA-GSH had a negative zeta potential of -6.21 mv. The maximum protein load for nanoparticles based on Ch-GSH and based on PAA-GSH was 45 +/- 2% and 37 +/- %, respectively. The release profile of nanoparticles followed a first order release kinetic. Thiolated nanoparticles prepared by a high pressure homogenization technique were shown to be stable and provide controlled drug release characteristics. The preparation method described here might be a useful tool for a more upscaled production of nanoparticulate drug delivery systems. PMID:20367028

  13. Lipid nanoparticles for topical and transdermal application for alopecia treatment: development, physicochemical characterization, and in vitro release and penetration studies.

    PubMed

    Gomes, Maria João; Martins, Susana; Ferreira, Domingos; Segundo, Marcela A; Reis, Salette

    2014-01-01

    Alopecia is a dermatological disorder, commonly known as hair loss, which affects up to half of the Caucasian male population by middle age, and almost all (95%) Caucasian men by old age. Considering that alopecia affects so many people and that there is currently no scientifically proven treatment with few side effects, new drug-delivery systems able to improve alopecia therapy are urgently required. With this purpose in mind, the present study aimed to develop lipid nanoparticles (nanostructured lipid carriers) with the ability to incorporate and deliver anti-alopecia active compounds (minoxidil and finasteride) into the dermis and hair follicles. Lipid nanoparticles, prepared by ultrasonication method, showed mean particle sizes around 200 nm, which is sufficient for reaching the dermis and hair follicles, and zeta potential values around -30 mV, which indicates good physical stability. Over 28 days of storage, no significant variations in these parameters were observed, which indicates that all nanoformulations are stable in storage over that period. Cryo-scanning electron microscope measurements showed that all the lipid nanoparticles exhibited a spherical shape and a smooth surface regardless of their composition. Differential scanning calorimetry studies allowed the determination of phase transition temperatures and confirmed the recrystallization of the lipid nanoparticles (recrystallization index between 11% and 86%). A high loading efficiency was achieved for finasteride (between 70% and 90%), while less than 30% was achieved for minoxidil nanoparticles, over 28 days. Controlled release assays in physiological conditions demonstrated that nanoparticles loaded with minoxidil yielded a prolonged release, as desired. Penetration assays through pig ear skin demonstrated that nanoparticles loaded with minoxidil and finasteride had low levels of penetration. These results suggest that the proposed novel formulation presents several good characteristics

  14. Lipid nanoparticles for topical and transdermal application for alopecia treatment: development, physicochemical characterization, and in vitro release and penetration studies

    PubMed Central

    Gomes, Maria João; Martins, Susana; Ferreira, Domingos; Segundo, Marcela A; Reis, Salette

    2014-01-01

    Alopecia is a dermatological disorder, commonly known as hair loss, which affects up to half of the Caucasian male population by middle age, and almost all (95%) Caucasian men by old age. Considering that alopecia affects so many people and that there is currently no scientifically proven treatment with few side effects, new drug-delivery systems able to improve alopecia therapy are urgently required. With this purpose in mind, the present study aimed to develop lipid nanoparticles (nanostructured lipid carriers) with the ability to incorporate and deliver anti-alopecia active compounds (minoxidil and finasteride) into the dermis and hair follicles. Lipid nanoparticles, prepared by ultrasonication method, showed mean particle sizes around 200 nm, which is sufficient for reaching the dermis and hair follicles, and zeta potential values around −30 mV, which indicates good physical stability. Over 28 days of storage, no significant variations in these parameters were observed, which indicates that all nanoformulations are stable in storage over that period. Cryo-scanning electron microscope measurements showed that all the lipid nanoparticles exhibited a spherical shape and a smooth surface regardless of their composition. Differential scanning calorimetry studies allowed the determination of phase transition temperatures and confirmed the recrystallization of the lipid nanoparticles (recrystallization index between 11% and 86%). A high loading efficiency was achieved for finasteride (between 70% and 90%), while less than 30% was achieved for minoxidil nanoparticles, over 28 days. Controlled release assays in physiological conditions demonstrated that nanoparticles loaded with minoxidil yielded a prolonged release, as desired. Penetration assays through pig ear skin demonstrated that nanoparticles loaded with minoxidil and finasteride had low levels of penetration. These results suggest that the proposed novel formulation presents several good characteristics

  15. Cell membrane damage and protein interaction induced by copper containing nanoparticles--importance of the metal release process.

    PubMed

    Karlsson, Hanna L; Cronholm, Pontus; Hedberg, Yolanda; Tornberg, Malin; De Battice, Laura; Svedhem, Sofia; Wallinder, Inger Odnevall

    2013-11-01

    Cu-containing nanoparticles are used in various applications in order to e.g. achieve antimicrobial activities and to increase the conductivity of fluids and polymers. Several studies have reported on toxic effects of such particles but the mechanisms are not completely clear. The aim of this study was to investigate the interactions between cell membranes and well-characterized nanoparticles of CuO, Cu metal, a binary Cu-Zn alloy and micron-sized Cu metal particles. This was conducted via in vitro investigations of the effects of the nanoparticles on (i) cell membrane damage on lung epithelial cells (A549), (ii) membrane rupture of red blood cells (hemolysis), complemented by (iii) nanoparticle interaction studies with a model lipid membrane using quartz crystal microbalance with dissipation monitoring (QCM-D). The results revealed that nanoparticles of the Cu metal and the Cu-Zn alloy were both highly membrane damaging and caused a rapid (within 1h) increase in membrane damage at a particle mass dose of 20 μg/mL, whereas the CuO nanoparticles and the micron-sized Cu metal particles showed no such effect. At similar nanoparticle surface area doses, the nano and micron-sized Cu particles showed more similar effects. The commonly used LDH (lactate dehydrogenase) assay for analysis of membrane damage was found impossible to use due to nanoparticle-assay interactions. None of the particles induced any hemolytic effects on red blood cells when investigated up to high particle concentrations (1mg/mL). However, both Cu and Cu-Zn nanoparticles caused hemoglobin aggregation/precipitation, a process that would conceal a possible hemolytic effect. Studies on interactions between the nanoparticles and a model membrane using QCM-D indicated a small difference between the investigated particles. Results of this study suggest that the observed membrane damage is caused by the metal release process at the cell membrane surface and highlight differences in reactivity between

  16. Oral delivery of insulin via polyethylene imine-based nanoparticles for colonic release allows glycemic control in diabetic rats.

    PubMed

    Salvioni, Lucia; Fiandra, Luisa; Del Curto, Maria Dorly; Mazzucchelli, Serena; Allevi, Raffaele; Truffi, Marta; Sorrentino, Luca; Santini, Benedetta; Cerea, Matteo; Palugan, Luca; Corsi, Fabio; Colombo, Miriam

    2016-08-01

    In this study, insulin-containing nanoparticles were loaded into pellet cores and orally administered to diabetic rats. Polyethylene imine-based nanoparticles, either placebo or loaded with insulin, were incorporated by extrusion and spheronization technology into cores that were subsequently coated with three overlapping layers and a gastroresistant film. The starting and coated systems were evaluated in vitro for their physico-technololgical characteristics, as well as disintegration and release performance. Nanoparticles-loaded cores showed homogeneous particle size distribution and shape. When a superdisintegrant and a soluble diluent were included in the composition enhanced disintegration and release performance were observed. The selected formulations, coated either with enteric or three-layer films, showed gastroresistant and release delayed behavior in vitro, respectively. The most promising formulations were finally tested for their hypoglycemic effect in diabetic rats. Only the nanoformulations loaded into the three-layer pellets were able to induce a significant hypoglycemic activity in diabetic rats. Our results suggest that this efficient activity could be attributed to a retarded release of insulin into the distal intestine, characterized by relatively low proteolytic activity and optimal absorption. PMID:27181095

  17. Protease-mediated release of chemotherapeutics from mesoporous silica nanoparticles to ex vivo human and mouse lung tumors.

    PubMed

    van Rijt, Sabine H; Bölükbas, Deniz A; Argyo, Christian; Datz, Stefan; Lindner, Michael; Eickelberg, Oliver; Königshoff, Melanie; Bein, Thomas; Meiners, Silke

    2015-03-24

    Nanoparticles allow for controlled and targeted drug delivery to diseased tissues and therefore bypass systemic side effects. Spatiotemporal control of drug release can be achieved by nanocarriers that respond to elevated levels of disease-specific enzymes. For example, matrix metalloproteinase 9 (MMP9) is overexpressed in tumors, is known to enhance the metastatic potency of malignant cells, and has been associated with poor prognosis of lung cancer. Here, we report the synthesis of mesoporous silica nanoparticles (MSNs) tightly capped by avidin molecules via MMP9 sequence-specific linkers to allow for site-selective drug delivery in high-expressing MMP9 tumor areas. We provide proof-of-concept evidence for successful MMP9-triggered drug release from MSNs in human tumor cells and in mouse and human lung tumors using the novel technology of ex vivo 3D lung tissue cultures. This technique allows for translational testing of drug delivery strategies in diseased mouse and human tissue. Using this method we show MMP9-mediated release of cisplatin, which induced apoptotic cell death only in lung tumor regions of Kras mutant mice, without causing toxicity in tumor-free areas or in healthy mice. The MMP9-responsive nanoparticles also allowed for effective combinatorial drug delivery of cisplatin and proteasome inhibitor bortezomib, which had a synergistic effect on the (therapeutic) efficiency. Importantly, we demonstrate the feasibility of MMP9-controlled drug release in human lung tumors.

  18. Protease-mediated release of chemotherapeutics from mesoporous silica nanoparticles to ex vivo human and mouse lung tumors.

    PubMed

    van Rijt, Sabine H; Bölükbas, Deniz A; Argyo, Christian; Datz, Stefan; Lindner, Michael; Eickelberg, Oliver; Königshoff, Melanie; Bein, Thomas; Meiners, Silke

    2015-03-24

    Nanoparticles allow for controlled and targeted drug delivery to diseased tissues and therefore bypass systemic side effects. Spatiotemporal control of drug release can be achieved by nanocarriers that respond to elevated levels of disease-specific enzymes. For example, matrix metalloproteinase 9 (MMP9) is overexpressed in tumors, is known to enhance the metastatic potency of malignant cells, and has been associated with poor prognosis of lung cancer. Here, we report the synthesis of mesoporous silica nanoparticles (MSNs) tightly capped by avidin molecules via MMP9 sequence-specific linkers to allow for site-selective drug delivery in high-expressing MMP9 tumor areas. We provide proof-of-concept evidence for successful MMP9-triggered drug release from MSNs in human tumor cells and in mouse and human lung tumors using the novel technology of ex vivo 3D lung tissue cultures. This technique allows for translational testing of drug delivery strategies in diseased mouse and human tissue. Using this method we show MMP9-mediated release of cisplatin, which induced apoptotic cell death only in lung tumor regions of Kras mutant mice, without causing toxicity in tumor-free areas or in healthy mice. The MMP9-responsive nanoparticles also allowed for effective combinatorial drug delivery of cisplatin and proteasome inhibitor bortezomib, which had a synergistic effect on the (therapeutic) efficiency. Importantly, we demonstrate the feasibility of MMP9-controlled drug release in human lung tumors. PMID:25703655

  19. Oral delivery of insulin via polyethylene imine-based nanoparticles for colonic release allows glycemic control in diabetic rats.

    PubMed

    Salvioni, Lucia; Fiandra, Luisa; Del Curto, Maria Dorly; Mazzucchelli, Serena; Allevi, Raffaele; Truffi, Marta; Sorrentino, Luca; Santini, Benedetta; Cerea, Matteo; Palugan, Luca; Corsi, Fabio; Colombo, Miriam

    2016-08-01

    In this study, insulin-containing nanoparticles were loaded into pellet cores and orally administered to diabetic rats. Polyethylene imine-based nanoparticles, either placebo or loaded with insulin, were incorporated by extrusion and spheronization technology into cores that were subsequently coated with three overlapping layers and a gastroresistant film. The starting and coated systems were evaluated in vitro for their physico-technololgical characteristics, as well as disintegration and release performance. Nanoparticles-loaded cores showed homogeneous particle size distribution and shape. When a superdisintegrant and a soluble diluent were included in the composition enhanced disintegration and release performance were observed. The selected formulations, coated either with enteric or three-layer films, showed gastroresistant and release delayed behavior in vitro, respectively. The most promising formulations were finally tested for their hypoglycemic effect in diabetic rats. Only the nanoformulations loaded into the three-layer pellets were able to induce a significant hypoglycemic activity in diabetic rats. Our results suggest that this efficient activity could be attributed to a retarded release of insulin into the distal intestine, characterized by relatively low proteolytic activity and optimal absorption.

  20. Modeling the transport and retention of nC60 nanoparticles in the subsurface under different release scenarios.

    PubMed

    Bai, Chunmei; Li, Yusong

    2012-08-01

    The escalating production and consumption of engineered nanomaterials may lead to their increased release into groundwater. A number of studies have revealed the potential human health effects and aquatic toxicity of nanomaterials. Understanding the fate and transport of engineered nanomaterials is very important for evaluating their potential risks to human and ecological health. While there has been a great deal of research effort focused on the potential risks of nanomaterials, a limited amount of work has evaluated the transport of engineered nanomaterials under different release scenarios in a typical layered geological field setting. In this work, we simulated the transport of fullerene aggregates (nC(60)), a widely used engineered nanomaterial, in a multi-dimensional environment. A Modular Three-Dimensional Multispecies Transport Model (MT3DMS) was modified to evaluate the transport and retention of nC(60) nanoparticles. Hypothetical scenarios for the introduction of nanomaterials into the subsurface environment were investigated, including the release from an injection well and the release from a waste site. Under the conditions evaluated, the mobility of nC(60) nanoparticles was found to be very sensitive to the release scenario, release concentration, aggregate size, collision efficiency factor, and dispersivity of the nanomaterial. PMID:22683828

  1. Association of the physical and chemical properties and the cytotoxicity of metal oxide nanoparticles: metal ion release, adsorption ability and specific surface area.

    PubMed

    Horie, Masanori; Fujita, Katsuhide; Kato, Haruhisa; Endoh, Shigehisa; Nishio, Keiko; Komaba, Lilian Kaede; Nakamura, Ayako; Miyauchi, Arisa; Kinugasa, Shinichi; Hagihara, Yoshihisa; Niki, Etsuo; Yoshida, Yasukazu; Iwahashi, Hitoshi

    2012-04-01

    Association of cellular influences and physical and chemical properties were examined for 24 kinds of industrial metal oxide nanoparticles: ZnO, CuO, NiO, Sb(2)O(3), CoO, MoO(3), Y(2)O(3), MgO, Gd(2)O(3), SnO(2), WO(3), ZrO(2), Fe(2)O(3), TiO(2), CeO(2), Al(2)O(3), Bi(2)O(3), La(2)O(3), ITO, and cobalt blue pigments. We prepared a stable medium dispersion for each nanoparticle and examined the influence on cell viability and oxidative stress together with physical and chemical characterizations. ZnO, CuO, NiO, MgO, and WO(3) showed a large amount of metal ion release in the culture medium. The cellular influences of these soluble nanoparticles were larger than insoluble nanoparticles. TiO(2), SnO(2), and CeO(2) nanoparticles showed strong protein adsorption ability; however, cellular influences of these nanoparticles were small. The primary particle size and the specific surface area seemed unrelated to cellular influences. Cellular influences of metal oxide nanoparticles depended on the kind and concentrations of released metals in the solution. For insoluble nanoparticles, the adsorption property was involved in cellular influences. The primary particle size and specific surface area of metal oxide nanoparticles did not affect directly cellular influences. In conclusion the most important cytotoxic factor of metal oxide nanoparticles was metal ion release.

  2. Hyaluronidase-sensitive nanoparticle templates for triggered release of HIV/AIDS microbicide in vitro.

    PubMed

    Agrahari, Vivek; Zhang, Chi; Zhang, Tao; Li, Wenjing; Gounev, Todor K; Oyler, Nathan A; Youan, Bi-Botti C

    2014-03-01

    This study was designed to test the hypothesis that a triggered release of a topical microbicide (tenofovir) from hyaluronic acid nanoparticles (HA-NPs) can be achieved under the influence of hyaluronidase (HAase) enzyme. A fractional factorial experimental design was used to examine the factors [molar concentrations of adipic acid dihydrazide (X1) and 1-ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride (X2), volume of acetone (X3) and reaction time (X4)] influencing the responses, Y1; particle mean diameter: PMD (nanometers: nm), Y2; polydispersity index: PDI and Y3; zeta (ζ) potential: (millivolts). The amide bond formation between HA and ADH after cross-linking was confirmed by FT-IR and (13)C-NMR analyses. These NPs were also characterized for cytotoxicity on a human vaginal epithelial cell line and L. crispatus. When formulated with factors X1; 2.49 mM, X2; 9.96 mM, X3; 60 mL, X4; 6 h, HA-NPs exhibited a spherical shape with PMD, PDI, ζ potential, encapsulation efficiency, and drug loading of 70.6 ± 4.1 nm, 0.07 ± 0.02, -38.2 ± 2.8 mV, 51.8 ± 2.4% w/w and 26.1 ± 1.2% w/w, respectively, (n = 3). Unlike for HA based gel, HAase significantly triggered the drug release and HA degradation from the NPs after 24 h (~90% w/w and 65% w/w, respectively); whereas, in its absence, these values were ~39% w/w and 26% w/w, respectively. The NPs were non-cytotoxic to human vaginal VK2/E6E7, End1/E6E7 cells and Lactobacillus crispatus. These data highlight the potential of HAase-sensitive HA-NPs templates for the controlled and vaginal delivery of anti-HIV/AIDS microbicides. PMID:24343770

  3. Poly(ε-caprolactone)/triclosan loaded polylactic acid nanoparticles composite: A long-term antibacterial bionanocomposite with sustained release.

    PubMed

    Kaffashi, Babak; Davoodi, Saeed; Oliaei, Erfan

    2016-07-11

    In this study, the antibacterial bionanocomposites of poly(ε-caprolactone) (PCL) with different concentrations of triclosan (TC) loaded polylactic acid (PLA) nanoparticles (30wt% triclosan) (LATC30) were fabricated via a melt mixing process in order to lower the burst release of PCL and to extend the antibacterial activity during its performance. Due to the PLA's higher glass transition temperature (Tg) and less flexibility compared with PCL; the PLA nanoparticles efficiently trapped the TC particles, reduced the burst release of TC from the bionanocomposites; and extended the antibacterial property of the samples up to two years. The melt mixing temperature was adjusted to a temperature lower than the melting point of LATC30 nanoparticles; therefore, these nanoparticles were dispersed in the PCL matrix without any chemical reaction and/or drug extraction. The sustained release behavior of TC from PCL remained unchanged since no significant changes occurred in the samples' crystallinity compared with that in the neat PCL. The elastic moduli of samples were enhanced once LATC30 is included. This is necessary since the elastic modulus is decreased with water absorption. The rheological behaviors of samples showed appropriate properties for melt electro-spinning. A stable process was established as the relaxation time of the bionanocomposites was increased. The hydrophilic properties of samples were increased with increasing LATC30. The proliferation rate of the fibroblast (L929) cells was enhanced as the content of nanoparticles was increased. A system similar to this could be implemented to prepare long-term antibacterial and drug delivery systems based on PCL and various low molecular weight drugs. The prepared bionanocomposites are considered as candidates for the soft connective tissue engineering and long-term drug delivery.

  4. pH-responsive deoxyribonucleic acid capture/release by polydopamine functionalized magnetic nanoparticles.

    PubMed

    Wang, Yu; Ma, Xiangdong; Ding, Chun; Jia, Li

    2015-03-01

    Polydopamine functionalized magnetic nanoparticles (PDA@Fe3O4) were prepared and characterized by transmission electron microscopy, scanning electron microscopy, zeta potential and vibrating sample magnetometry. They were found to enable highly efficient capture of genomic deoxyribonucleic acid (DNA). The adsorption capacity of PDA@Fe3O4 for genomic DNA can reach 161 mg g(-1). The extraction protocol used aqueous solutions for DNA binding to and releasing from the surface of the magnetic particles based on the pH inducing the charge switch of amino and phenolic hydroxyl groups on PDA@Fe3O4. The extracted DNA with high quality (A260/A280=1.80) can be directly used as templates for polymerase chain reaction (PCR) followed by capillary electrophoresis (CE) analysis. None of the toxic chemical reagents and PCR inhibitors was used throughout the whole procedure. PDA@Fe3O4 based magnetic solid phase extraction (MSPE) method was superior to those using commercial kit and traditional phenol-chloroform extraction methods in yield of DNA. The developed PDA@Fe3O4 based MSPE-PCR-CE method was applied for simultaneous and fast detection of Listeria monocytogenes and Escherichia coli O157:H7 in milk. PMID:25682426

  5. Thyrotropin-Releasing Hormone Loaded and Chitosan Engineered Polymeric Nanoparticles: Towards Effective Delivery of Neuropeptides.

    PubMed

    Kaur, Sarabjit; Bhararia, Avani; Sharma, Krishna; Mittal, Sherry; Jain, Rahul; Wangoo, Nishima; Sharma, Rohit K

    2016-05-01

    Thyrotropin-Releasing Hormone (TRH), a tripeptide amide with molecular formula L-pGlu-L-His-L- Pro-NH2, is used in the treatment of brain/spinal injury and certain central nervous system (CNS) disorders, including schizophrenia, Alzheimer's disease, epilepsy, depression, shock and ischemia due to its profound effects on the CNS. However, TRH's therapeutic activity is severely hampered because of instability and hydrophilicity owing to its peptidic nature which results into ineffective penetration into the blood brain barrier. In the present study, we report the synthesis and stability studies of novel chitosan engineered TRH encapsulated poly(lactide-co-glycolide) (PLGA) based nanoformulation. The aim of such an encapsulation is to allow effective delivery of TRH in biological systems as the peptidase degrade naked TRH. The synthesis of TRH was carried out manually in solution phase followed by its encapsulation using PLGA to form polymeric nanoparticles (NPs) via nanoprecipitation technique. Different parameters such as type of organic phase, concentration of stabilizer, ratio of organic phase and aqueous phase, rate of addition of organic phase were optimized, tested and evaluated for particle size, encapsulation efficiency, and stability of NPs. The TRH-PLGA NPs were then surface modified with chitosan to achieve positive surface charge rendering them potential membrane penetrating agents. PLGA, PLGA-TRH, Chitosan-PLGA and Chitosan-PLGA-TRH NPs were characterized and analyzed using Dynamic Light Scattering (DLS), Transmissiom Electron Microscopy (TEM) and Infra-red spectroscopic techniques. PMID:27483926

  6. Oral fast-release solid dispersion-paradigm shift to nanoparticles.

    PubMed

    Wong, Tin W

    2011-09-01

    Design of oral fast-release solid dispersion of poorly water-soluble drugs has been a great challenge over past decades on issues of drug recrystallization, drug polymorphism, formulation limited to low drug-to-carrier ratio and drug particle aggregation in matrix. The complexity in solid dispersion design is envisaged to be resolvable by the use of nanoparticulate system as solid dosage form. This manuscript reviews several patented processing approaches of nanoparticulate solid dispersion that have been reported recently. Through drug nanoencapsulation, a higher content of drug may be delivered with less aggregation via placing the same drug mass in a greater number of tinier carriers. Nanoencapsulation, by its own process of formation, brings about submicron particles. Keeping drug in these nanoparticles, a remarkable rise in specific surface area of drug is realized for dissolution. The augmentation of drug dissolution can be sufficiently high to the extent that the influences of polymorphism and crystallization phenomenon on drug dissolution in a solid dispersion may be negligible. PMID:21834774

  7. Tegafur loading and release properties of magnetite/poly(alkylcyanoacrylate) (core/shell) nanoparticles.

    PubMed

    Arias, José L; Ruiz, M Adolfina; Gallardo, Visitación; Delgado, Angel V

    2008-01-01

    In this work, we describe a reproducible method to prepare polymeric colloidal nanospheres of poly(ethyl-2-cyanoacrylate), poly(butylcyanoacrylate), poly(hexylcyanoacrylate) and poly(octylcyanoacrylate) with a magnetite core, and loaded with the anticancer drug Tegafur. The method is based on the emulsion polymerization procedure, often used in the synthesis of poly(alkylcyanoacrylate) nanospheres for drug delivery. The heterogeneous structure of the particles confer them both magnetic-field responsiveness and potential applicability as drug carriers. In order to investigate to what extent is this target achieved, we compare the surface electrical properties of the core/shell particles with those of both the nucleus and the coating material. The hysteresis cycles of both magnetite and composite particles demonstrate that the polymer shell reduces the magnetic responsiveness of the particles, but keeps their soft ferrimagnetic character unchanged. A detailed investigation of the capabilities of the core/shell particles to load this drug is shown. We found, by means of spectrophotometric and electrophoretic measurements, the existence of two drug loading mechanisms: absorption or entrapment in the polymeric network, and surface adsorption. The type of polymer, the pH and the drug concentration are the main factors determining the drug incorporation to the nanoparticles. The release studies showed a biphasic profile affected by the type of polymeric shell, the type of drug incorporation and the amount of drug loaded.

  8. The Antimicrobial Properties of Silver Nanoparticles in Bacillus subtilis Are Mediated by Released Ag+ Ions

    PubMed Central

    Hsueh, Yi-Huang; Lin, Kuen-Song; Ke, Wan-Ju; Hsieh, Chien-Te; Chiang, Chao-Lung; Tzou, Dong-Ying; Liu, Shih-Tung

    2015-01-01

    The superior antimicrobial properties of silver nanoparticles (Ag NPs) are well-documented, but the exact mechanisms underlying Ag-NP microbial toxicity remain the subject of intense debate. Here, we show that Ag-NP concentrations as low as 10 ppm exert significant toxicity against Bacillus subtilis, a beneficial bacterium ubiquitous in the soil. Growth arrest and chromosomal DNA degradation were observed, and flow cytometric quantification of propidium iodide (PI) staining also revealed that Ag-NP concentrations of 25 ppm and above increased membrane permeability. RedoxSensor content analysis and Phag-GFP expression analysis further indicated that reductase activity and cytosolic protein expression decreased in B. subtilis cells treated with 10–50 ppm of Ag NPs. We conducted X-ray absorption near-edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) analyses to directly clarify the valence and fine structure of Ag atoms in B. subtilis cells placed in contact with Ag NPs. The results confirmed the Ag species in Ag NP-treated B. subtilis cells as Ag2O, indicating that Ag-NP toxicity is likely mediated by released Ag+ ions from Ag NPs, which penetrate bacterial cells and are subsequently oxidized intracellularly to Ag2O. These findings provide conclusive evidence for the role of Ag+ ions in Ag-NP microbial toxicity, and suggest that the impact of inappropriately disposed Ag NPs to soil and water ecosystems may warrant further investigation. PMID:26669836

  9. The Antimicrobial Properties of Silver Nanoparticles in Bacillus subtilis Are Mediated by Released Ag+ Ions.

    PubMed

    Hsueh, Yi-Huang; Lin, Kuen-Song; Ke, Wan-Ju; Hsieh, Chien-Te; Chiang, Chao-Lung; Tzou, Dong-Ying; Liu, Shih-Tung

    2015-01-01

    The superior antimicrobial properties of silver nanoparticles (Ag NPs) are well-documented, but the exact mechanisms underlying Ag-NP microbial toxicity remain the subject of intense debate. Here, we show that Ag-NP concentrations as low as 10 ppm exert significant toxicity against Bacillus subtilis, a beneficial bacterium ubiquitous in the soil. Growth arrest and chromosomal DNA degradation were observed, and flow cytometric quantification of propidium iodide (PI) staining also revealed that Ag-NP concentrations of 25 ppm and above increased membrane permeability. RedoxSensor content analysis and Phag-GFP expression analysis further indicated that reductase activity and cytosolic protein expression decreased in B. subtilis cells treated with 10-50 ppm of Ag NPs. We conducted X-ray absorption near-edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) analyses to directly clarify the valence and fine structure of Ag atoms in B. subtilis cells placed in contact with Ag NPs. The results confirmed the Ag species in Ag NP-treated B. subtilis cells as Ag2O, indicating that Ag-NP toxicity is likely mediated by released Ag+ ions from Ag NPs, which penetrate bacterial cells and are subsequently oxidized intracellularly to Ag2O. These findings provide conclusive evidence for the role of Ag+ ions in Ag-NP microbial toxicity, and suggest that the impact of inappropriately disposed Ag NPs to soil and water ecosystems may warrant further investigation. PMID:26669836

  10. Layer-by-layer engineering fluorescent polyelectrolyte coated mesoporous silica nanoparticles as pH-sensitive nanocarriers for controlled release

    NASA Astrophysics Data System (ADS)

    Du, Pengcheng; Zhao, Xubo; Zeng, Jin; Guo, Jinshan; Liu, Peng

    2015-08-01

    Fluorescent core/shell composite has been fabricated by the layer-by-layer (LbL) assembly of the fluorescein isothiocyanate modified chitosan (CS-FITC) and sodium alginate (AL) onto the carboxyl modified mesoporous silica nanoparticles (MSN-COOH), followed by PEGylation. It exhibits stability in high salt-concentration media and the pH responsive fluorescent feature can be used for cell imaging. Furthermore, the modified MSN cores can enhance the DOX loading capacity and the multifunctional polyelectrolyte shell can adjust the drug release upon the media pH, showing a low leakage quantity at the neutral environment but significantly enhanced release at lower pH media mimicking the tumor environments. Therefore, the biocompatible fluorescent polyelectrolyte coated mesoporous silica nanoparticles (MSN-LBL-PEG) offer promise for tumor therapy.

  11. Synthesis and characterisation of chitosan crosslinked-β-cyclodextrin grafted silylated magnetic nanoparticles for controlled release of Indomethacin

    NASA Astrophysics Data System (ADS)

    Anirudhan, T. S.; Dilu, D.; Sandeep, S.

    2013-10-01

    In this work, a novel hydrogel, chitosan crosslinked β-cyclodextrin grafted silylated magnetic nanoparticle (CTSCD-g-SilylMNP) was synthesised as a drug delivery system onto which Indomethacin (IND) drug was loaded. Characterisation of the drug delivery system was carried out by Tunnelling electron microscopy, Scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction analysis, Dynamic light scattering and a Vibrating sample magnetometer. Swelling behaviour, in vitro drug release kinetics, and encapsulation efficiency of CTSCD-g-SilylMNP were studied. Swelling behaviour varied according to pH. In vitro release studies revealed that CTSCD-g-SilylMNP demonstrated a swelling and diffusion controlled release. Dependence of pH was also studied. Encapsulation efficiency (EE) at different percentages of drug loadings was studied. The results collectively suggest that the hydrogel has promising application in the field of controlled drug release. The biodegradability also adds to the advantage.

  12. Controlled release hydrogen sulfide delivery system based on mesoporous silica nanoparticles protects graft endothelium from ischemia–reperfusion injury

    PubMed Central

    Wang, Wenshuo; Sun, Xiaotian; Zhang, Huili; Yang, Cheng; Liu, Ye; Yang, Wuli; Guo, Changfa; Wang, Chunsheng

    2016-01-01

    Hydrogen sulfide (H2S) functions as a protective gas transmitter in various physiological and pathological processes, but the lack of ideal donors severely hampers the clinical application of H2S. This study aims to construct a controlled release H2S donor and evaluate its protective effect on graft endothelium. Mesoporous silica nanoparticles (MSNs) were synthesized using the sol–gel method and loaded with diallyl trisulfide (DATS), an H2S-releasing agent named DATS-MSN. In vitro experiments showed that DATS-MSN could alleviate endothelial cell inflammation and enhance endothelial cell proliferation and migration. In vivo experiments demonstrated that the apoptosis of graft endothelium was mitigated in the presence of DATS-MSN. Our results indicated that DATS-MSN, releasing H2S in a controlled release fashion, could serve as an ideal H2S donor. PMID:27486324

  13. Controlled release hydrogen sulfide delivery system based on mesoporous silica nanoparticles protects graft endothelium from ischemia-reperfusion injury.

    PubMed

    Wang, Wenshuo; Sun, Xiaotian; Zhang, Huili; Yang, Cheng; Liu, Ye; Yang, Wuli; Guo, Changfa; Wang, Chunsheng

    2016-01-01

    Hydrogen sulfide (H2S) functions as a protective gas transmitter in various physiological and pathological processes, but the lack of ideal donors severely hampers the clinical application of H2S. This study aims to construct a controlled release H2S donor and evaluate its protective effect on graft endothelium. Mesoporous silica nanoparticles (MSNs) were synthesized using the sol-gel method and loaded with diallyl trisulfide (DATS), an H2S-releasing agent named DATS-MSN. In vitro experiments showed that DATS-MSN could alleviate endothelial cell inflammation and enhance endothelial cell proliferation and migration. In vivo experiments demonstrated that the apoptosis of graft endothelium was mitigated in the presence of DATS-MSN. Our results indicated that DATS-MSN, releasing H2S in a controlled release fashion, could serve as an ideal H2S donor. PMID:27486324

  14. Non-invasive controlled release from gold nanoparticle integrated photo-responsive liposomes through pulse laser induced microbubble cavitation.

    PubMed

    Mathiyazhakan, Malathi; Yang, Yuanxiang; Liu, Yibo; Zhu, Caigang; Liu, Quan; Ohl, Claus-Dieter; Tam, Kam Chiu; Gao, Yu; Xu, Chenjie

    2015-02-01

    Drug-carriers, capable of releasing the drug at the target sites upon external stimuli, are attractive for theranostic applications. In recent years, photo-responsive nanoparticles (NPs) have received considerable attention because of their potentials in providing spatial, temporal, and dosage control over the drug release. However, most of the relevant technologies are still in the process of development and are unprocurable by the clinics. Here, we demonstrated facile fabrication of these photo-responsive NPs by loading hydrophilic gold NPs within thermo-responsive liposomes. Calcein was used as a model drug to evaluate the encapsulation efficiency and the release kinetic profile upon heat/light stimulation. Furthermore, we characterized their size, morphology, phase transition temperature and stability. Finally, we demonstrated that this photo-triggered release might be due to the membrane disruption caused by microbubble cavitation.

  15. Stabilizing Alginate Confinement and Polymer Coating of CO-Releasing Molecules Supported on Iron Oxide Nanoparticles To Trigger the CO Release by Magnetic Heating.

    PubMed

    Meyer, Hajo; Winkler, Felix; Kunz, Peter; Schmidt, Annette M; Hamacher, Alexandra; Kassack, Matthias U; Janiak, Christoph

    2015-12-01

    Maghemite (Fe2O3) iron oxide nanoparticles (IONPs) were synthesized, modified with covalent surface-bound CO-releasing molecules of a tri(carbonyl)-chlorido-phenylalaninato-ruthenium(II) complex (CORM), and coated with a dextran polymer. The time- and temperature-dependent CO release from this CORM-3 analogue was followed by a myoglobin assay. A new measurement method for the myoglobin assay was developed, based on confining "water-soluble" polymer-coated Dextran500k@CORM@IONP particles in hollow spheres of nontoxic and easily prepared calcium alginate. Dropping a mixture of Dextran500k@CORM@IONP and sodium alginate into a CaCl2 solution leads to stable hollow spheres of Ca(2+) cross-linked alginate which contain the Dextran500k@CORM@IONP particles. This "alginate-method" (i) protects CORM-3 analogues from rapid CO-displacement reactions with a protein, (ii) enables a spatial separation of the CORM from its surrounding myoglobin assay with the alginate acting as a CO-permeable membrane, and (iii) allows the use of substances with high absorptivity (such as iron oxide nanoparticles) in the myoglobin assay without interference in the optical path of the UV cell. Embedding the CORM@IONP nanoparticles in the alginate vessel represents a compartmentation of the reactive component and allows for close contact with, yet facile separation from, the surrounding myoglobin assay. The half-life of the CO release from Dextran500k@CORM@IONP particles surrounded by alginate was determined to be 890 ± 70 min at 20 °C. An acceleration of the CO release occurs at higher temperature with a half-life of 172 ± 27 min at 37 °C and 45 ± 7 min at 50 °C. The CO release can be triggered in an alternating current magnetic field (31.7 kA m(-1), 247 kHz, 39.9 mT) through local magnetic heating of the susceptible iron oxide nanoparticles. With magnetic heating at 20 °C in the bulk solution, the half-life of CO release from Dextran500k@CORM@IONP particles decreased to 155 ± 18 min

  16. Avidin-biotin capped mesoporous silica nanoparticles as an ion-responsive release system to determine lead(II).

    PubMed

    Song, Weiling; Li, Jingyu; Li, Qing; Ding, Wenyao; Yang, Xiaoyan

    2015-02-15

    We have developed DNAzyme-functionalized silica nanoparticles for the rapid, sensitive, and selective detection of lead ion (Pb(2+)). The specific binding between avidin and biotinylated DNAzymes was used to cap the pore of dye-trapped silica nanoparticles. In the presence of Pb(2+), DNAzymes were catalytically cleaved to uncap the pore, releasing the dye cargo with detectable enhancements of fluorescence signal. This method enables rapid (15 min) and sensitive (limit of detection=8.0 nM) detection. Moreover, the Pb(2+)-responsive behavior shows high selectivity with other metal ions. The superior properties of the as-designed DNAzyme-functionalized silica nanoparticles can be attributed to the large loading capacity and highly ordered pore structure of mesoporous silica nanoparticles as well as the catalytical cleaving of DNAzymes with Pb(2+). The recoveries obtained by standard Pb(II) addition to real samples-tap water, commercial mineral water, and lake water-were all from 98 to 101%. Our design serves as a new prototype for metal-ion sensing systems, and it also has promising potential for detection of various targets in stimulus-release systems. PMID:25447495

  17. Dual-drug delivery by porous silicon nanoparticles for improved cellular uptake, sustained release, and combination therapy.

    PubMed

    Wang, Chang-Fang; Mäkilä, Ermei M; Kaasalainen, Martti H; Hagström, Marja V; Salonen, Jarno J; Hirvonen, Jouni T; Santos, Hélder A

    2015-04-01

    Dual-drug delivery of antiangiogenic and chemotherapeutic drugs can enhance the therapeutic effect for cancer therapy. Conjugation of methotrexate (MTX) to porous silicon (PSi) nanoparticles (MTX-PSi) with positively charged surface can improve the cellular uptake of MTX and inhibit the proliferation of cancer cells. Herein, MTX-PSi conjugates sustained the release of MTX up to 96 h, and the released fragments including MTX were confirmed by mass spectrometry. The intracellular distribution of the MTX-PSi nanoparticles was confirmed by transmission electron microscopy. Compared to pure MTX, the MTX-PSi achieved similar inhibition of cell proliferation in folate receptor (FR) over-expressing U87 MG cancer cells, and a higher effect in low FR-expressing EA.hy926 cells. Nuclear fragmentation analysis demonstrated programmed cell apoptosis of MTX-PSi in the high/low FR-expressing cancer cells, whereas PSi alone at the same dose had a minor effect on cell apoptosis. Finally, the porous structure of MTX-PSi enabled a successful concomitant loading of another anti-angiogenic hydrophobic drug, sorafenib, and considerably enhanced the dissolution rate of sorafenib. Overall, the MTX-PSi nanoparticles can be used as a platform for combination chemotherapy by simultaneously enhancing the dissolution rate of a hydrophobic drug and sustaining the release of a conjugated chemotherapeutic drug.

  18. Polymeric emulsion and crosslink-mediated synthesis of super-stable nanoparticles as sustained-release anti-tuberculosis drug carriers.

    PubMed

    Choonara, Yahya E; Pillay, Viness; Ndesendo, Valence M K; du Toit, Lisa C; Kumar, Pradeep; Khan, Riaz A; Murphy, Caragh S; Jarvis, Debbie-Leigh

    2011-10-15

    This study focused on evaluating four emulsion-based processing strategies for polymeric nanoparticle synthesis to explicate the mechanisms of nanoparticle formation and the influence on achieving sustained-release of two anti-tuberculosis drugs, isoniazid and rifampicin. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles were formulated with and without sorbitan mono-oleate as a stabilizer using emulsion-solvent-surfactant-evaporation (ESSE) and emulsion-solvent-evaporation (ESE) approaches. An alginate solution gelled by ionic crosslinking with calcium chloride was employed to prepare alginate hydrogel nanoparticles via reverse-emulsion-cationic-gelification (RECG) and reverse-emulsion-surfactant-cationic-gelification (RESCG) approaches. In vitro drug release analysis was performed. The size, zeta potential and morphology of the nanoparticles were analyzed. Molecular mechanics energy relationships (MMER) were employed to explore the spatial disposition of alginate and PLGA with respect to the emulsifying profile of sorbitan monooleate and to corroborate the experimental findings. Results revealed that particle size of the PLGA nanoparticles was influenced by the stabilizer concentration. Nanoparticles synthesized by the ESSE approach had smaller sizes of 240±8.7 nm and 195.5±5.4 nm for rifampicin- and isoniazid-loaded nanoparticles, respectively. This was a substantial size reduction from nanoparticles generated by the ESE approach (>1000 nm). The RESCG approach produced stable and higher nanoparticle yields with desirable size (277±1.0 nm; 289±1.2 nm), a low polydispersity index (27.1±0.3 mV; 28.5±0.5 mV) and drug entrapment efficiency of 73% and 75% for isoniazid and rifampicin, respectively. Drug release from the ESSE and RESCG synthesized nanoparticles displayed desirable release of the two anti-TB drugs with sustained zero-order kinetics over a period of 8h. MMER supported the mechanisms of nanoparticle formation with a sphericalized interlaced network

  19. In situ synthesis of silver-nanoparticles/bacterial cellulose composites for slow-released antimicrobial wound dressing.

    PubMed

    Wu, Jian; Zheng, Yudong; Song, Wenhui; Luan, Jiabin; Wen, Xiaoxiao; Wu, Zhigu; Chen, Xiaohua; Wang, Qi; Guo, Shaolin

    2014-02-15

    Bacterial cellulose has attracted increasing attention as a novel wound dressing material, but it has no antimicrobial activity, which is one of critical skin-barrier functions in wound healing. To overcome such deficiency, we developed a novel method to synthesize and impregnate silver nanoparticles on to bacterial cellulose nanofibres (AgNP-BC). Uniform spherical silver nano-particles (10-30 nm) were generated and self-assembled on the surface of BC nano-fibers, forming a stable and evenly distributed Ag nanoparticles coated BC nanofiber. Such hybrid nanostructure prevented Ag nanoparticles from dropping off BC network and thus minimized the toxicity of nanoparticles. Regardless the slow Ag(+) release, AgNP-BC still exhibited significant antibacterial activities with more than 99% reductions in Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa. Moreover, AgNP-BC allowed attachment and growth of epidermal cells with no cytotoxicity emerged. The results demonstrated that AgNP-BC could reduce inflammation and promote wound healing. PMID:24507345

  20. Tailoring the internal structure of liquid crystalline nanoparticles responsive to fungal lipases: A potential platform for sustained drug release.

    PubMed

    Poletto, F S; Lima, F S; Lundberg, D; Nylander, T; Loh, W

    2016-11-01

    Lipases are key components in the mechanisms underlying the persistence and virulence of infections by fungi, and thus also promising triggers for bioresponsive lipid-based liquid crystalline nanoparticles. We here propose a platform in which only a minor component of the formulation is susceptible to cleavage by lipase and where hydrolysis triggers a controlled phase transition within the nanoparticles that can potentially allow for an extended drug release. The responsive formulations were composed of phytantriol, which was included as a non-cleavable major component and polysorbate 80, which serves both as nanoparticle stabilizer and potential lipase target. To monitor the structural changes resulting from lipase activity with sufficient time resolution, we used synchrotron small angle x-ray scattering. Comparing the effect of the two different lipases used in this work, lipase B from Candida Antarctica, (CALB) and lipase from Rhizomucor miehei (RMML), only CALB induced phase transition from bicontinuous reverse cubic to reverse hexagonal phase within the particles. This phase transition can be attributed to an increasing amount of oleic acid formed on cleavage of the polysorbate 80. However, when also a small amount of a cationic surfactant was included in the formulation, RMML could trigger the corresponding phase transition as well. The difference in activity between the two lipases can tentatively be explained by a difference in their interaction with the nanoparticle surface. Thus, a bioresponsive system for treating fungal infections, with a tunable selectivity for different types of lipases, could be obtained by tuning the composition of the nanoparticle formulation.

  1. Fabrication of hybrid nanocomposite scaffolds by incorporating ligand-free hydroxyapatite nanoparticles into biodegradable polymer scaffolds and release studies.

    PubMed

    Farkas, Balazs; Rodio, Marina; Romano, Ilaria; Diaspro, Alberto; Intartaglia, Romuald; Beke, Szabolcs

    2015-01-01

    We report on the optical fabrication approach of preparing free-standing composite thin films of hydroxyapatite (HA) and biodegradable polymers by combining pulsed laser ablation in liquid and mask-projection excimer laser stereolithography (MPExSL). Ligand-free HA nanoparticles were prepared by ultrafast laser ablation of a HA target in a solvent, and then the nanoparticles were dispersed into the liquid polymer resin prior to the photocuring process using MPExSL. The resin is poly(propylene fumarate) (PPF), a photo-polymerizable, biodegradable material. The polymer is blended with diethyl fumarate in 7:3 w/w to adjust the resin viscosity. The evaluation of the structural and mechanical properties of the fabricated hybrid thin film was performed by means of SEM and nanoindentation, respectively, while the chemical and degradation studies were conducted through thermogravimetric analysis, and FTIR. The photocuring efficiency was found to be dependent on the nanoparticle concentration. The MPExSL process yielded PPF thin films with a stable and homogenous dispersion of the embedded HA nanoparticles. Here, it was not possible to tune the stiffness and hardness of the scaffolds by varying the laser parameters, although this was observed for regular PPF scaffolds. Finally, the gradual release of the hydroxyapatite nanoparticles over thin film biodegradation is reported. PMID:26734513

  2. Fabrication of hybrid nanocomposite scaffolds by incorporating ligand-free hydroxyapatite nanoparticles into biodegradable polymer scaffolds and release studies

    PubMed Central

    Farkas, Balazs; Rodio, Marina; Romano, Ilaria; Diaspro, Alberto; Intartaglia, Romuald

    2015-01-01

    Summary We report on the optical fabrication approach of preparing free-standing composite thin films of hydroxyapatite (HA) and biodegradable polymers by combining pulsed laser ablation in liquid and mask-projection excimer laser stereolithography (MPExSL). Ligand-free HA nanoparticles were prepared by ultrafast laser ablation of a HA target in a solvent, and then the nanoparticles were dispersed into the liquid polymer resin prior to the photocuring process using MPExSL. The resin is poly(propylene fumarate) (PPF), a photo-polymerizable, biodegradable material. The polymer is blended with diethyl fumarate in 7:3 w/w to adjust the resin viscosity. The evaluation of the structural and mechanical properties of the fabricated hybrid thin film was performed by means of SEM and nanoindentation, respectively, while the chemical and degradation studies were conducted through thermogravimetric analysis, and FTIR. The photocuring efficiency was found to be dependent on the nanoparticle concentration. The MPExSL process yielded PPF thin films with a stable and homogenous dispersion of the embedded HA nanoparticles. Here, it was not possible to tune the stiffness and hardness of the scaffolds by varying the laser parameters, although this was observed for regular PPF scaffolds. Finally, the gradual release of the hydroxyapatite nanoparticles over thin film biodegradation is reported. PMID:26734513

  3. Hyaluronate nanoparticles included in polymer films for the prolonged release of vitamin E for the management of skin wounds.

    PubMed

    Pereira, Gabriela Garrastazu; Detoni, Cassia Britto; Balducci, Anna Giulia; Rondelli, Valeria; Colombo, Paolo; Guterres, Silvia Stanisçuaski; Sonvico, Fabio

    2016-02-15

    Lecithin and hyaluronic acid were used for the preparation of polysaccharide decorated nanoparticles loaded with vitamin E using the cationic lipid dioctadecyldimethylammonium bromide (DODMA). Nanoparticles showed mean particle size in the range 130-350 nm and narrow size distribution. Vitamin E encapsulation efficiency was higher than 99%. These nanoparticles were incorporated in polymeric films containing Aloe vera extract, hyaluronic acid, sodium alginate, polyethyleneoxide (PEO) and polyvinylalcohol (PVA) as an innovative treatment in skin wounds. Films were thin, flexible, resistant and suitable for application on burn wounds. Additionally, in vitro occlusion study highlighted the dependence of the occlusive effect on the presence of nanoparticles. The results obtained show that the bioadhesive films containing vitamin E acetate and Aloe vera could be an innovative therapeutic system for the treatment of skin wounds, such as burns. The controlled release of the vitamin along with a reduction in water loss through damaged skin provided by the nanoparticle-loaded polymer film are considered important features for an improvement in wound healing and skin regeneration. PMID:26769495

  4. Poly(acrylic acid)-block-poly(vinyl alcohol) anchored maghemite nanoparticles designed for multi-stimuli triggered drug release

    NASA Astrophysics Data System (ADS)

    Liu, Ji; Detrembleur, Christophe; Debuigne, Antoine; de Pauw-Gillet, Marie-Claire; Mornet, Stéphane; Vander Elst, Luce; Laurent, Sophie; Labrugère, Christine; Duguet, Etienne; Jérôme, Christine

    2013-11-01

    Original core/corona nanoparticles composed of a maghemite core and a stimuli-responsive polymer coating made of poly(acrylic acid)-block-poly(vinyl alcohol) macromolecules were fabricated for drug delivery system (DDS) application. This kind of DDS aims to combine the advantage of stimuli-responsive polymer coating, in order to regulate the drug release behaviours under different conditions and furthermore, improve the biocompatibility and in vivo circulation half-time of the maghemite nanoparticles. Drug loading capacity was evaluated with methylene blue (MB), a cationic model drug. The triggered release of MB was studied under various stimuli such as pH, ionic strength and temperature. Local heating generated under alternating magnetic field (AMF) application was studied, and remotely AMF-triggered release was also confirmed, while a mild heating-up of the release medium was observed. Furthermore, their potential application as magnetic resonance imaging (MRI) contrast agents was explored via relaxivity measurements and acquisition of T2-weighted images. Preliminary studies on the cytotoxicity against mouse fibroblast-like L929 cell line and also their cellular uptake within human melanoma MEL-5 cell line were carried out. In conclusion, this kind of stimuli-responsive nanoparticles appears to be promising carriers for delivering drugs to some tumour sites or into cellular compartments with an acidic environment.Original core/corona nanoparticles composed of a maghemite core and a stimuli-responsive polymer coating made of poly(acrylic acid)-block-poly(vinyl alcohol) macromolecules were fabricated for drug delivery system (DDS) application. This kind of DDS aims to combine the advantage of stimuli-responsive polymer coating, in order to regulate the drug release behaviours under different conditions and furthermore, improve the biocompatibility and in vivo circulation half-time of the maghemite nanoparticles. Drug loading capacity was evaluated with methylene

  5. Analytical assessment about the simultaneous quantification of releasable pharmaceutical relevant inorganic nanoparticles in tap water and domestic waste water.

    PubMed

    Krystek, Petra; Bäuerlein, Patrick S; Kooij, Pascal J F

    2015-03-15

    For pharmaceutical applications, the use of inorganic engineered nanoparticles is of growing interest while silver (Ag) and gold (Au) are the most relevant elements. A few methods were developed recently but the validation and the application testing were quite limited. Therefore, a routinely suitable multi element method for the identification of nanoparticles of different sizes below 100 nm and elemental composition by applying asymmetric flow field flow fraction (AF4) - inductively coupled plasma mass spectrometry (ICPMS) is developed. A complete validation model of the quantification of releasable pharmaceutical relevant inorganic nanoparticles based on Ag and Au is presented for the most relevant aqueous matrices of tap water and domestic waste water. The samples are originated from locations in the Netherlands and it is of great interest to study the unwanted presence of Ag and Au as nanoparticle residues due to possible health and environmental risks. During method development, instability effects are observed for 60 nm and 70 nm Ag ENPs with different capping agents. These effects are studied more closely in relation to matrix effects. Besides the methodological aspects, the obtained analytical results and relevant performance characteristics (e.g. measuring range, limit of detection, repeatability, reproducibility, trueness, and expanded uncertainty of measurement) are determined and discussed. For the chosen aqueous matrices, the results of the performance characteristics are significantly better for Au ENPs in comparison to Ag ENPs; e.g. repeatability and reproducibility are below 10% for all Au ENPs respectively maximal 27% repeatability for larger Ag ENPs. The method is a promising tool for the simultaneous determination of releasable pharmaceutical relevant inorganic nanoparticles.

  6. Nickel Release, ROS Generation and Toxicity of Ni and NiO Micro- and Nanoparticles

    PubMed Central

    Hedberg, Jonas; Di Bucchianico, Sebastiano; Möller, Lennart; Odnevall Wallinder, Inger; Elihn, Karine; Karlsson, Hanna L.

    2016-01-01

    Occupational exposure to airborne nickel is associated with an elevated risk for respiratory tract diseases including lung cancer. Therefore, the increased production of Ni-containing nanoparticles necessitates a thorough assessment of their physical, chemical, as well as toxicological properties. The aim of this study was to investigate and compare the characteristics of nickel metal (Ni) and nickel oxide (NiO) particles with a focus on Ni release, reactive oxygen species (ROS) generation, cellular uptake, cytotoxicity and genotoxicity. Four Ni-containing particles of both nano-size (Ni-n and NiO-n) and micron-size (Ni-m1 and Ni-m2) were tested. The released amount of Ni in solution was notably higher in artificial lysosomal fluid (e.g. 80–100 wt% for metallic Ni) than in cell medium after 24h (ca. 1–3 wt% for all particles). Each of the particles was taken up by the cells within 4 h and they remained in the cells to a high extent after 24 h post-incubation. Thus, the high dissolution in ALF appeared not to reflect the particle dissolution in the cells. Ni-m1 showed the most pronounced effect on cell viability after 48 h (alamar blue assay) whereas all particles showed increased cytotoxicity in the highest doses (20–40 μg cm2) when assessed by colony forming efficiency (CFE). Interestingly an increased CFE, suggesting higher proliferation, was observed for all particles in low doses (0.1 or 1 μg cm-2). Ni-m1 and NiO-n were the most potent in causing acellular ROS and DNA damage. However, no intracellular ROS was detected for any of the particles. Taken together, micron-sized Ni (Ni-m1) was more reactive and toxic compared to the nano-sized Ni. Furthermore, this study underlines that the low dose effect in terms of increased proliferation observed for all particles should be further investigated in future studies. PMID:27434640

  7. Nickel Release, ROS Generation and Toxicity of Ni and NiO Micro- and Nanoparticles.

    PubMed

    Latvala, Siiri; Hedberg, Jonas; Di Bucchianico, Sebastiano; Möller, Lennart; Odnevall Wallinder, Inger; Elihn, Karine; Karlsson, Hanna L

    2016-01-01

    Occupational exposure to airborne nickel is associated with an elevated risk for respiratory tract diseases including lung cancer. Therefore, the increased production of Ni-containing nanoparticles necessitates a thorough assessment of their physical, chemical, as well as toxicological properties. The aim of this study was to investigate and compare the characteristics of nickel metal (Ni) and nickel oxide (NiO) particles with a focus on Ni release, reactive oxygen species (ROS) generation, cellular uptake, cytotoxicity and genotoxicity. Four Ni-containing particles of both nano-size (Ni-n and NiO-n) and micron-size (Ni-m1 and Ni-m2) were tested. The released amount of Ni in solution was notably higher in artificial lysosomal fluid (e.g. 80-100 wt% for metallic Ni) than in cell medium after 24h (ca. 1-3 wt% for all particles). Each of the particles was taken up by the cells within 4 h and they remained in the cells to a high extent after 24 h post-incubation. Thus, the high dissolution in ALF appeared not to reflect the particle dissolution in the cells. Ni-m1 showed the most pronounced effect on cell viability after 48 h (alamar blue assay) whereas all particles showed increased cytotoxicity in the highest doses (20-40 μg cm2) when assessed by colony forming efficiency (CFE). Interestingly an increased CFE, suggesting higher proliferation, was observed for all particles in low doses (0.1 or 1 μg cm-2). Ni-m1 and NiO-n were the most potent in causing acellular ROS and DNA damage. However, no intracellular ROS was detected for any of the particles. Taken together, micron-sized Ni (Ni-m1) was more reactive and toxic compared to the nano-sized Ni. Furthermore, this study underlines that the low dose effect in terms of increased proliferation observed for all particles should be further investigated in future studies. PMID:27434640

  8. Sucrose ester stabilized solid lipid nanoparticles and nanostructured lipid carriers: I. Effect of formulation variables on the physicochemical properties, drug release and stability of clotrimazole-loaded nanoparticles

    NASA Astrophysics Data System (ADS)

    Das, Surajit; Kiong Ng, Wai; Tan, Reginald B. H.

    2014-03-01

    The objective of this study was to develop and evaluate solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) utilizing sucrose ester as a stabilizer/emulsifier for the controlled release of drug/active. Both SLNs and NLCs were prepared using different sugar esters to screen out the most suitable stabilizer. Clotrimazole was used as a model active/drug. The effect of different formulation variables on the particle size, polydispersity index and drug encapsulation efficiency of SLNs and NLCs was evaluated and compared. SLNs and NLCs were physicochemically characterized and compared using Cryo-SEM, DSC and XRD. Furthermore, a drug release study of SLNs and NLCs was conducted. Finally, physicochemical stability (size, PI, ZP, EE) of the SLNs and NLCs was checked at 25 ± 2 °C and at 2-8 °C. Among the sucrose esters, D-1216 was found to be most suitable for both SLNs and NLCs. Formulation variables exhibited a significant impact on size, PI and EE of the nanoparticles. SLNs with ˜120 nm size, ˜0.23 PI, ˜I26I mV ZP, ˜87% EE and NLCs with ˜160 nm size, 0.15 PI, ˜I26I mV ZP, ˜88% EE were produced. Cryo-SEM revealed spherical particles with a smooth surface but did not exhibit any difference in surface morphology between SLNs and NLCs. DSC and XRD results demonstrated the disappearance of clotrimazole peak(s) in drug-loaded SLNs and NLCs. Faster drug release was observed from SLNs than NLCs. NLCs were found to be more stable than SLNs in terms of size, PI, EE and drug release. The results indicated that both SLNs and NLCs stabilized with sucrose ester D-1216 can be used as controlled release carriers although NLCs have an edge over SLNs.

  9. Mussel-inspired polydopamine coated mesoporous silica nanoparticles as pH-sensitive nanocarriers for controlled release.

    PubMed

    Zheng, Qishan; Lin, Tianran; Wu, Hanyin; Guo, Liangqia; Ye, Peirong; Hao, Yanli; Guo, Qingquan; Jiang, Jinzhi; Fu, Fengfu; Chen, Guonan

    2014-03-10

    A novel pH-sensitive controlled release system is proposed by using mussel-inspired polydopamine (PDA) coated mesoporous silica nanoparticles (MSNs) as nanocarriers. MSNs with a large pore diameter are synthesized by using 1,3,5-trimethylbenzene as a pore-expanding agent and are modified with a PDA coating by virtue of oxidative self-polymerization of dopamine in neutral pH. PDA coated MSNs are characterized by FTIR, TEM, N₂ adsorption and XPS techniques. The PDA coating can work as pH-sensitive gatekeepers to control the release of drug molecules from MSNs in response to the pH-stimulus. Doxorubicin (DOX, an anticancer drug) can be released in the acid media and blocked in the neutral media. PMID:24393764

  10. Novel, silver-ion-releasing nanofibrous scaffolds exhibit excellent antibacterial efficacy without the use of silver nanoparticles.

    PubMed

    Mohiti-Asli, Mahsa; Pourdeyhimi, Behnam; Loboa, Elizabeth G

    2014-05-01

    Nanofibers, with their morphological similarities to the extracellular matrix of skin, hold great potential for skin tissue engineering. Over the last decade, silver nanoparticles have been extensively investigated in wound-healing applications for their ability to provide antimicrobial benefits to nanofibrous scaffolds. However, the use of silver nanoparticles has raised concerns as these particles can penetrate into the stratum corneum of skin, or even diffuse into the cellular plasma membrane. We present and evaluate a new silver ion release polymeric coating that we have found can be applied to biocompatible, biodegradable poly(l-lactic acid) nanofibrous scaffolds. Using this compound, custom antimicrobial silver-ion-releasing nanofibers were created. The presence of a uniform, continuous silver coating on the nanofibrous scaffolds was verified by XPS analysis. The antimicrobial efficacy of the antimicrobial scaffolds against Staphylococcus aureus and Escherichia coli bacteria was determined via industry-standard AATCC protocols. Cytotoxicity analyses of the antimicrobial scaffolds toward human epidermal keratinocytes and human dermal fibroblasts were performed via quantitative analyses of cell viability and proliferation. Our results indicated that the custom antimicrobial scaffolds exhibited excellent antimicrobial properties while also maintaining human skin cell viability and proliferation for silver ion concentrations below 62.5μgml(-1) within the coating solution. This is the first study to show that silver ions can be effectively delivered with nanofibrous scaffolds without the use of silver nanoparticles.

  11. Novel surfactant for preparation of poly(L-lactic acid) nanoparticles with controllable release profile and cytocompatibility for drug delivery.

    PubMed

    Li, Fengjuan; Zhu, Aiping; Song, Xiaoli; Ji, Lijun

    2014-03-01

    Poly(L-lactic acid) nanoparticles loaded with a hydrophobic drug were prepared by an emulsion-evaporation process (oil in water) with a novel, effective and biocompatible surfactant butanedioic acid, 2-sulfo-1,4-butanedioic acid ditridecyl ester (sodium salt, 1:1) (BASDE). The particles are spherical in morphology and their diameters are controllable from 50 to 550nm with poly-dispersity indexes within the range of 0.122-0.340. The drug entrapment efficiency and drug content were measured by spectrophotometry. The drug release rate is affected by both the size of the particles and the drug content in the particles. In vitro cytotoxicity data indicate that these drug-loaded PLA nanoparticles are safe for hypodermic injection regard to the toxicological acceptance. This study demonstrates that using BASDE surfactant, the size of PLA nanoparticles can be controlled at the nanoscale with a narrow size distribution, and the drug release is controllable with excellent in vitro cytocompatibility. This may be due to efficient emulsification capability and biocompatibility of BASDE. PMID:24503291

  12. A comparison of the dechlorination mechanisms and Ni release styles of chloroalkane and chloroalkene removal using nickel/iron nanoparticles.

    PubMed

    Zhang, Wei; Jia, Nan; Han, Xiaolin; Qiu, Zhaofu; Lv, Shuguang; Lin, Kuangfei; Ying, Weichi

    2016-08-01

    In this study, we compared the removal kinetics and Ni release styles of 1,1,1-trichloroethane (1,1,1-TCA), trichloroethylene (TCE), and tetrachloroethene (PCE) that result from the use of Ni/Fe nanoparticles in water. Compared to TCE and PCE, 1,1,1-TCA was more readily removed, and the concentration profiles of the three chlorinated aliphatic hydrocarbons (CAHs) during the reduction processes fit pseudo-first-order reaction rate models well. The surface area-normalized rate constants show that the 11% Ni Ni/Fe nanoparticles, which has the largest Brunauer-Emmett-Teller surface area, has the highest capacity for 1,1,1-TCA removal per unit surface area and that the 6% Ni sample was the best for removing TCE and PCE. The observed by-products suggested that hydrogenolysis was responsible for the dechlorination of CAHs in the presence of Ni/Fe nanoparticles. More Ni2+ was released during the degradation of 1,1,1-TCA than that of TCE and PCE because Ni will reduce the CAHs directly as a zerovalent metal does when hydrogen atoms in the Ni lattice are not sufficient due to the rapid incomplete dechlorination of 1,1,1-TCA. The different modes of adsorption of chloroalkane and chloroalkene onto the surfaces of Ni/Fe particles might play an important role in their dechlorination process. PMID:26776083

  13. Targeted Drug Delivery with Polymers and Magnetic Nanoparticles: Covalent and Noncovalent Approaches, Release Control, and Clinical Studies.

    PubMed

    Ulbrich, Karel; Holá, Kateřina; Šubr, Vladimir; Bakandritsos, Aristides; Tuček, Jiří; Zbořil, Radek

    2016-05-11

    Targeted delivery combined with controlled drug release has a pivotal role in the future of personalized medicine. This review covers the principles, advantages, and drawbacks of passive and active targeting based on various polymer and magnetic iron oxide nanoparticle carriers with drug attached by both covalent and noncovalent pathways. Attention is devoted to the tailored conjugation of targeting ligands (e.g., enzymes, antibodies, peptides) to drug carrier systems. Similarly, the approaches toward controlled drug release are discussed. Various polymer-drug conjugates based, for example, on polyethylene glycol (PEG), N-(2-hydroxypropyl)methacrylamide (HPMA), polymeric micelles, and nanoparticle carriers are explored with respect to absorption, distribution, metabolism, and excretion (ADME scheme) of administrated drug. Design and structure of superparamagnetic iron oxide nanoparticles (SPION) and condensed magnetic clusters are classified according to the mechanism of noncovalent drug loading involving hydrophobic and electrostatic interactions, coordination chemistry, and encapsulation in porous materials. Principles of covalent conjugation of drugs with SPIONs including thermo- and pH-degradable bonds, amide linkage, redox-cleavable bonds, and enzymatically-cleavable bonds are also thoroughly described. Finally, results of clinical trials obtained with polymeric and magnetic carriers are analyzed highlighting the potential advantages and future directions in targeted anticancer therapy.

  14. Silver nanoparticles influence on the blood activation process and their release to blood plasma from synthetic polymer scaffold

    NASA Astrophysics Data System (ADS)

    Major, R.; Lackner, J. M.; Sanak, M.; Major, B.

    2016-03-01

    In the present work, blood and blood plasma interaction to silver stabilised polyelectrolytes was investigated in vitro. The designed materials are dedicated for regeneration of the cardiovascular system. Silver nanoparticles were introduced into the polyelectrolyte structure in order to reduce the risk of bacterial biofilm formation. The introduction of Ag nanoparticles occurred by deposition at high vacuum by magnetron sputtering. The analysis of blood-materials interactions were performed by using commercially available tester, Impact-R (Diamed). The assessment of silver ion nanoparticles release into the plasma consisted in determining the Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT). Unmodified surface of polyelectrolytes is a strong activator for blood elements. The introduction of silver nanoparticles resulted in a significant reduction in the probability of clotting. The extrinsic pathway of coagulation determined on the basis of the PT and the intrinsic and common pathways of coagulation measured by the APTT did not indicate the danger out of range. Microstructure was studied using TEM on thin foils prepared from the cross-section of samples subjected to biomedical treatments. The observations revealed hetero- interface between two different crystalline solids.

  15. Controlled release of drug and better bioavailability using poly(lactic acid-co-glycolic acid) nanoparticles.

    PubMed

    Pandey, Sanjeev K; Patel, Dinesh K; Maurya, Akhilendra K; Thakur, Ravi; Mishra, Durga P; Vinayak, Manjula; Haldar, Chandana; Maiti, Pralay

    2016-08-01

    Tamoxifen (Tmx) embedded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (PLGA-Tmx) is prepared to evaluate its better DNA cleavage potential, cytotoxicity using Dalton's lymphoma ascite (DLA) cells and MDA-MB231 breast cancer cells. PLGA-Tmx nanoparticles are prepared through emulsified nanoprecipitation technique with varying dimension of 17-30nm by changing the concentrations of polymer, emulsifier and drug. Nanoparticles dimension are measured through electron and atomic force microscopy. Interactions between tamoxifen and PLGA are verified through spectroscopic and calorimetric methods. PLGA-Tmx shows excellent DNA cleavage potential as compared to pure Tmx raising better bioavailability. In vitro cytotoxicity studies indicate that PLGA-Tmx reduces DLA cells viability up to ∼38% against ∼15% in pure Tmx. Hoechst stain is used to detect apoptotic DLA cells through fluorescence imaging of nuclear fragmentation and condensation exhibiting significant increase of apoptosis (70%) in PLGA-Tmx vis-à-vis pure drug (58%). Enhanced DNA cleavage potential, nuclear fragmentation and condensation in apoptotic cells confirm greater bioavailability of PLGA-Tmx as compared to pure Tmx in terms of receptor mediated endocytosis. Hence, the sustained release kinetics of PLGA-Tmx nanoparticles shows much better anticancer efficacy through enhanced DNA cleavage potential and nuclear fragmentation and, thereby, reveal a novel vehicle for the treatment of cancer. PMID:27112980

  16. Drug Release Kinetics, Cell Uptake, and Tumor Toxicity of Hybrid VVVVVVKK Peptide-Assembled Polylactide Nanoparticles

    PubMed Central

    Jabbari, Esmaiel; Yang, Xiaoming; Moeinzadeh, Seyedsina; He, Xuezhong

    2013-01-01

    An exciting approach to tumor delivery is encapsulation of the drug in self-assembled polymer-peptide nanoparticles. The objective of this work was to synthesize a conjugate of low molecular weight polylactide (LMW PLA) and V6K2 peptide, and investigate self-assembly, drug release kinetics, cell uptake and toxicity, drug pharmacokinetics, and tumor cell invasion with Doxorubicin (DOX) or paclitaxel (PTX). The results for PLA-V6K2 self-assembled NPs were compared with those of polyethylene glycol stabilized PLA (PLA-EG) NPs. The size of PLA-V6K2 and PLA-EG NPs were 100±20 and 130±50 nm, respectively, with polydispersity index of 1.04 and 1.14. The encapsulation efficiency of DOX in PLA-V6K2 and PLA-EG NPs was 44±9% and 55±5%, respectively, and that of PTX was >90 for both NP types. The release of DOX and PTX from PLA-V6K2 was slower than that of PLA-EG and the release rate was relatively constant with time. Based on molecular dynamic simulation, the less hydrophobic DOX was distributed in the lactide core as well as the peptide shell while the hydrophobic PTX was localized mainly to the lactide core. PLA-V6K2 NPs had significantly higher cell uptake by 4T1 mouse breast carcinoma cells compared to PLA-EG NPs, which was attributed to the electrostatic interactions between the peptide and negatively charged moieties on the cell membrane. PLA-V6K2 NPs showed no toxicity to marrow stromal cells. DOX loaded PLA-V6K2 NPs showed higher toxicity to 4T1 cells and the DNA damage response and apoptosis was delayed compared to the free DOX. DOX or PTX encapsulated in PLA-V6K2 NPs significantly reduced invasion of 4T1 cells compared to those cells treated with the drug in PLA-EG NPs. Invasion of 4T1 cells treated with DOX in PLA-V6K2 and PLA-EG NPs was 5±1% and 30±5%, respectively, and that of PTX was 11±2% and 40±7%. The AUC of DOX in PLA-V6K2 NPs was 67% and 21% higher than those of free DOX and PLA-EG NPs, respectively. DOX loaded PLA-V6K2 NPs injected in C3He

  17. Analytical characteristics and application of novel chitosan coated magnetic nanoparticles as an efficient drug delivery system for ciprofloxacin. Enhanced drug release kinetics by low-frequency ultrasounds.

    PubMed

    Kariminia, Samira; Shamsipur, Ali; Shamsipur, Mojtaba

    2016-09-10

    A pH-responsive drug carrier based on chitosan coated iron oxide nanoparticles (CS-Fe3O4) for prolonged antibiotic release in a controlled manner is reported. As an antibiotic drug model, ciprofloxacin was loaded onto the nanocarrier via H-bonding interactions. The nanoparticles were characterized using scanning electron microscopy, X-ray diffraction, energy-dispersive X-ray spectroscopy, photon correlation spectroscopy and Fourier transform infrared spectroscopy. The particle size of CS-Fe3O4 nanoparticles were found to lie in the range of 30-80nm. The analytical characteristics of the designed system were thoroughly investigated. The in vitro drug loading at pH 4.8 and release kinetics at pH 7.4 studies revealed that the drug delivery system can take 99% of ciprofloxacin load and quantitatively release the drug over a sustained period of 5 days. The release kinetics study indicated that the system follows a zero order kinetics via a diffusion-controlled mechanism. These results indicated that CS-Fe3O4 nanoparticles have the potential for use as controlled antibiotic delivery systems through oral administration by avoiding the drug release in the highly acidic gastric fluid region of the stomach. Furthermore, the ability of low-frequency ultrasound in fast release of the encapsulated drug in less than 60min from the CS-Fe3O4 nanoparticles in a controlled manner was confirmed. PMID:27497305

  18. Development of a Controlled Release of Salicylic Acid Loaded Stearic Acid-Oleic Acid Nanoparticles in Cream for Topical Delivery

    PubMed Central

    Woo, J. O.; Misran, M.; Lee, P. F.; Tan, L. P.

    2014-01-01

    Lipid nanoparticles are colloidal carrier systems that have extensively been investigated for controlled drug delivery, cosmetic and pharmaceutical applications. In this work, a cost effective stearic acid-oleic acid nanoparticles (SONs) with high loading of salicylic acid, was prepared by melt emulsification method combined with ultrasonication technique. The physicochemical properties, thermal analysis and encapsulation efficiency of SONs were studied. TEM micrographs revealed that incorporation of oleic acid induces the formation of elongated spherical particles. This observation is in agreement with particle size analysis which also showed that the mean particle size of SONs varied with the amount of OA in the mixture but with no effect on their zeta potential values. Differential scanning calorimetry analysis showed that the SONs prepared in this method have lower crystallinity as compared to pure stearic acid. Different amount of oleic acid incorporated gave different degree of perturbation to the crystalline matrix of SONs and hence resulted in lower degrees of crystallinity, thereby improving their encapsulation efficiencies. The optimized SON was further incorporated in cream and its in vitro release study showed a gradual release for 24 hours, denoting the incorporation of salicylic acid in solid matrix of SON and prolonging the in vitro release. PMID:24578624

  19. Real-time observation of aortic vessel dilation through delivery of sodium nitroprusside via slow release mesoporous nanoparticles.

    PubMed

    Farooq, Asima; Tosheva, Lubomira; Azzawi, May; Whitehead, Debra

    2016-09-15

    Spherical mesoporous nanoparticles (MNPs) with a diameter of ∼100nm were synthesised via a sol-gel method in the presences of organic template (with and without fluorescein dye encapsulation). The template molecules were removed by acidic extraction to form a regular pore lattice structure. The nanoparticle size and morphology were analysed using transmission electron microscopy and dynamic light scattering analysis. The MNPs were further characterised by zeta potential, nitrogen adsorption measurements and infra-red spectroscopy. The interior pores had an average diameter of ∼3nm and were loaded with an endothelial-independent vasodilator, sodium nitroprusside (SNP). The optimal drug loading and drug release was determined in high potassium physiological salt solution using dialysis and atomic absorption spectroscopy. We demonstrate that the initial instantaneous release is due to the surface desorption of the drug followed by diffusion from the pores. Furthermore, these drug loaded MNPs (with and without fluorescein dye encapsulation) were added to viable aortic vessels and release in real-time was observed, ex vivo. MNPs and loaded with and without SNP were incubated with the vessel (at 1.96×10(12)NPmL(-1)) over a 3h time period. The real-time exposure to unloaded MNPs resulted in a small attenuation in constriction that occurred after approximately 1h. In contrast, MNPs loaded with SNP led to a rapid relaxation of aortic vessels that was sustained over the 3h period (p<0.001). PMID:27288578

  20. Development of a controlled release of salicylic acid loaded stearic acid-oleic acid nanoparticles in cream for topical delivery.

    PubMed

    Woo, J O; Misran, M; Lee, P F; Tan, L P

    2014-01-01

    Lipid nanoparticles are colloidal carrier systems that have extensively been investigated for controlled drug delivery, cosmetic and pharmaceutical applications. In this work, a cost effective stearic acid-oleic acid nanoparticles (SONs) with high loading of salicylic acid, was prepared by melt emulsification method combined with ultrasonication technique. The physicochemical properties, thermal analysis and encapsulation efficiency of SONs were studied. TEM micrographs revealed that incorporation of oleic acid induces the formation of elongated spherical particles. This observation is in agreement with particle size analysis which also showed that the mean particle size of SONs varied with the amount of OA in the mixture but with no effect on their zeta potential values. Differential scanning calorimetry analysis showed that the SONs prepared in this method have lower crystallinity as compared to pure stearic acid. Different amount of oleic acid incorporated gave different degree of perturbation to the crystalline matrix of SONs and hence resulted in lower degrees of crystallinity, thereby improving their encapsulation efficiencies. The optimized SON was further incorporated in cream and its in vitro release study showed a gradual release for 24 hours, denoting the incorporation of salicylic acid in solid matrix of SON and prolonging the in vitro release.

  1. Emulsion-based encapsulation and delivery of nanoparticles for the controlled release of alkalinity within the subsurface environment

    NASA Astrophysics Data System (ADS)

    Ramsburg, C. A.; Muller, K.; Gill, J.

    2012-12-01

    Many current approaches to managing groundwater contamination rely on further advances in amendment delivery in order to initiate and sustain contaminant degradation or immobilization. In fact, limited or ineffective delivery is often cited when treatment objectives are not attained. Emulsions, specifically oil-in-water emulsions, have demonstrated potential to aid delivery of remediation amendments. Emulsions also afford opportunities to control the release of active ingredients encapsulated within the droplets. Our research is currently focused on the controlled release of nanoparticle-based buffering agents using oil-in-water emulsions. This interest is motivated by the fact that chemical and biological processes employed for the remediation and stewardship of contaminated sites often necessitate control of pH during treatment and, in some cases, long thereafter. Alkalinity-release nanoparticles (e.g., CaCO3, MgO) were suspended within soybean oil and subsequently encapsulated by through the creation of oil-in-water emulsions. These oil-in-water emulsions are designed to have physical properties which are favorable for subsurface delivery (nominal properties: 1 g/mL density; 10 cP viscosity; and 1.5 μm droplet diameter). Buffer capacity titrations suggest that MgO particles are moderately more accessible within the oil phase and nearly twice as effective (on a per mass basis) at releasing alkalinity (as compared to the CaCO3 particles). Results from experiments designed to assess the release kinetics suggest that a linear driving force model is capable of describing the release process and mass transfer coefficients are constant through the reactive life of the emulsion. The release kinetics in emulsions containing MgO particles were found to be three orders of magnitude faster than those quantified for emulsions containing CaCO3. The slower release kinetics of the emulsions containing CaCO3 particles may prove beneficial when considering pH control at sites

  2. Tailoring the internal structure of liquid crystalline nanoparticles responsive to fungal lipases: A potential platform for sustained drug release.

    PubMed

    Poletto, F S; Lima, F S; Lundberg, D; Nylander, T; Loh, W

    2016-11-01

    Lipases are key components in the mechanisms underlying the persistence and virulence of infections by fungi, and thus also promising triggers for bioresponsive lipid-based liquid crystalline nanoparticles. We here propose a platform in which only a minor component of the formulation is susceptible to cleavage by lipase and where hydrolysis triggers a controlled phase transition within the nanoparticles that can potentially allow for an extended drug release. The responsive formulations were composed of phytantriol, which was included as a non-cleavable major component and polysorbate 80, which serves both as nanoparticle stabilizer and potential lipase target. To monitor the structural changes resulting from lipase activity with sufficient time resolution, we used synchrotron small angle x-ray scattering. Comparing the effect of the two different lipases used in this work, lipase B from Candida Antarctica, (CALB) and lipase from Rhizomucor miehei (RMML), only CALB induced phase transition from bicontinuous reverse cubic to reverse hexagonal phase within the particles. This phase transition can be attributed to an increasing amount of oleic acid formed on cleavage of the polysorbate 80. However, when also a small amount of a cationic surfactant was included in the formulation, RMML could trigger the corresponding phase transition as well. The difference in activity between the two lipases can tentatively be explained by a difference in their interaction with the nanoparticle surface. Thus, a bioresponsive system for treating fungal infections, with a tunable selectivity for different types of lipases, could be obtained by tuning the composition of the nanoparticle formulation. PMID:27518452

  3. pH-responsive glycol chitosan-cross-linked carboxymethyl-β-cyclodextrin nanoparticles for controlled release of anticancer drugs.

    PubMed

    Wang, Yiwen; Qin, Fei; Tan, Haina; Zhang, Yan; Jiang, Miao; Lu, Mei; Yao, Xin

    2015-01-01

    Carboxymethyl-β-cyclodextrin (CMβ-CD)-modified glycol chitosan (GCS) nanoparticles (GCS-CMβ-CD NPs) were synthesized, and their pH-sensitive drug-release properties were investigated. GCS-CMβ-CD NPs could encapsulate doxorubicin hydrochloride (DOX), and the encapsulation efficiency and loading capacity increased with the amount of CMβ-CD. Drug-release studies indicate that DOX released was greater in acidic medium (pH 5.0) than in weakly basic medium (pH 7.4). The mechanism underlying the pH-sensitive properties of the carrier was analyzed. Finally, the MCF-7 (human breast cancer) and SW480 cell lines (human colon cancer) were used to evaluate the cytotoxicity of the NPs. The drug-loaded carriers show good inhibition of the growth of cancer cells compared with free DOX, and the carriers have good biocompatibility. In addition, the drug-loaded NPs have sustained drug-release properties. All these properties of the newly synthesized GCS-CMβ-CD NPs suggest a promising potential as an effective anticancer drug-delivery system for controlled drug release. PMID:26677325

  4. The suppression of IgE-mediated histamine release from mast cells following exocytic exclusion of biodegradable polymeric nanoparticles.

    PubMed

    Tahara, Kohei; Tadokoro, Satoshi; Yamamoto, Hiromitsu; Kawashima, Yoshiaki; Hirashima, Naohide

    2012-01-01

    The objective of this study is to evaluate the effect of polymeric nanoparticles (NPs) on the allergic response of mast cells that release inflammatory mediators such as histamine through exocytosis. Submicron-sized biodegradable poly(DL-lactide-co-glycolide) (PLGA) NPs were prepared by the emulsion solvent diffusion method. Here, we examined the interactions of the mast cells with two types of PLGA NPs, unmodified NPs and NPs modified with chitosan (CS), a biodegradable cationic polymer. The cellular uptake of NPs increased by CS modification due to electrostatic interactions with the plasma membrane. NPs were taken up by mast cells through an endocytic pathway (endocytic phase) and then the cellular uptake was saturated and maintained plateau level by the exclusion of NPs through exocytosis (exocytic phase). Antigen-induced histamine release from mast cells was inhibited during the exocytic phase. The extent of histamine release inhibition was related to the amount of excluded NPs. Exocytic exclusion of NPs competitively antagonize the antigen-induced exocytotic release of histamine by highjacking exocytosis machinery such as SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins, since histamine release was recovered in mast cells that overexpress SNAP-23. The inhibitory effect of the allergic response by PLGA NPs was also evaluated in vivo using the mouse model for systemic anaphylaxis. The administration of NPs suppressed the antigen-induced systemic allergic response in vivo. In conclusion, PLGA NP itself has actions to inhibit the allergic responses mediated by mast cells.

  5. pH-responsive glycol chitosan-cross-linked carboxymethyl-β-cyclodextrin nanoparticles for controlled release of anticancer drugs

    PubMed Central

    Wang, Yiwen; Qin, Fei; Tan, Haina; Zhang, Yan; Jiang, Miao; Lu, Mei; Yao, Xin

    2015-01-01

    Carboxymethyl-β-cyclodextrin (CMβ-CD)-modified glycol chitosan (GCS) nanoparticles (GCS-CMβ-CD NPs) were synthesized, and their pH-sensitive drug-release properties were investigated. GCS-CMβ-CD NPs could encapsulate doxorubicin hydrochloride (DOX), and the encapsulation efficiency and loading capacity increased with the amount of CMβ-CD. Drug-release studies indicate that DOX released was greater in acidic medium (pH 5.0) than in weakly basic medium (pH 7.4). The mechanism underlying the pH-sensitive properties of the carrier was analyzed. Finally, the MCF-7 (human breast cancer) and SW480 cell lines (human colon cancer) were used to evaluate the cytotoxicity of the NPs. The drug-loaded carriers show good inhibition of the growth of cancer cells compared with free DOX, and the carriers have good biocompatibility. In addition, the drug-loaded NPs have sustained drug-release properties. All these properties of the newly synthesized GCS-CMβ-CD NPs suggest a promising potential as an effective anticancer drug-delivery system for controlled drug release. PMID:26677325

  6. 1-Acetylpyrene-salicylic acid: photoresponsive fluorescent organic nanoparticles for the regulated release of a natural antimicrobial compound, salicylic acid.

    PubMed

    Barman, Shrabani; Mukhopadhyay, Sourav K; Behara, Krishna Kalyani; Dey, Satyahari; Singh, N D Pradeep

    2014-05-28

    Photoresponsive 1-acetylpyrene-salicylic acid (AcPy-SA) nanoparticles (NPs) were developed for the regulated release of a natural antimicrobial compound, salicylic acid. The strong fluorescent properties of AcPy-SA NPs have been extensively used for potential in vitro cell imaging. The phototrigger capability of our newly prepared AcPy-SA NPs was utilized for the efficient release of an antimicrobial compound, salicylic acid. The photoregulated drug release of AcPy-SA NPs has been shown by the subsequent switching off and on of a visible-light source. In vitro biological studies reveal that AcPy-SA NPs of ∼68 nm size deliver the antimicrobial drug salicylic acid into the bacteria cells (Pseudomonas aeruginosa) and efficiently kill the cells upon exposure to visible light (≥410 nm). Such photoresponsive fluorescent organic NPs will be highly beneficial for targeted and regulated antimicrobial drug release because of their biocompatible nature, efficient cellular uptake, and light-induced drug release ability.

  7. Enhanced Anti-Tumoral Activity of Methotrexate-Human Serum Albumin Conjugated Nanoparticles by Targeting with Luteinizing Hormone-Releasing Hormone (LHRH) Peptide

    PubMed Central

    Taheri, Azade; Dinarvand, Rassoul; Atyabi, Fatemeh; Ahadi, Fatemeh; Nouri, Farank Salman; Ghahremani, Mohammad Hossein; Ostad, Seyed Nasser; Borougeni, Atefeh Taheri; Mansoori, Pooria

    2011-01-01

    Active targeting could increase the efficacy of anticancer drugs. Methotrexate-human serum albumin (MTX-HSA) conjugates, functionalized by luteinizing hormone-releasing hormone (LHRH) as targeting moieties, with the aim of specifically targeting the cancer cells, were prepared. Owing to the high expression of LHRH receptors in many cancer cells as compared to normal cells, LHRH was used as the targeting ligand in this study. LHRH was conjugated to MTX-HSA nanoparticles via a cross-linker. Three types of LHRH targeted nanoparticles with a mean particle size between 120–138 nm were prepared. The cytotoxicity of LHRH targeted and non-targeted nanoparticles were determined on the LHRH positive and negative cell lines. The internalization of the targeted and non-targeted nanoparticles in LHRH receptor positive and negative cells was investigated using flow cytometry analysis and fluorescence microscopy. The cytotoxicity of the LHRH targeted nanoparticles on the LHRH receptor positive cells were significantly more than non-targeted nanoparticles. LHRH targeted nanoparticles were also internalized by LHRH receptor positive cells significantly more than non-targeted nanoparticles. There were no significant differences between the uptake of targeted and non-targeted nanoparticles to the LHRH receptor negative cells. The active targeting procedure using LHRH targeted MTX-HSA nanoparticles could increase the anti-tumoral activity of MTX. PMID:21845098

  8. In Vitro Investigation of Self-Assembled Nanoparticles Based on Hyaluronic Acid-Deoxycholic Acid Conjugates for Controlled Release Doxorubicin: Effect of Degree of Substitution of Deoxycholic Acid

    PubMed Central

    Wei, Wen-Hao; Dong, Xue-Meng; Liu, Chen-Guang

    2015-01-01

    Self-assembled nanoparticles based on a hyaluronic acid-deoxycholic acid (HD) chemical conjugate with different degree of substitution (DS) of deoxycholic acid (DOCA) were prepared. The degree of substitution (DS) was determined by titration method. The nanoparticles were loaded with doxorubicin (DOX) as the model drug. The human cervical cancer (HeLa) cell line was utilized for in vitro studies and cell cytotoxicity of DOX incorporated in the HD nanoparticles was accessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, cellular uptake of fluorescently labeled nanoparticles was also investigated. An increase in the degree of deoxycholic acid substitution reduced the size of the nanoparticles and also enhanced their drug encapsulation efficiency (EE), which increased with the increase of DS. A higher degree of deoxycholic acid substitution also lead to a lower release rate and an initial burst release of doxorubicin from the nanoparticles. In summary, the degree of substitution allows the modulation of the particle size, drug encapsulation efficiency, drug release rate, and cell uptake efficiency of the nanoparticles. The herein developed hyaluronic acid-deoxycholic acid conjugates are a good candidate for drug delivery and could potentiate therapeutic formulations for doxorubicin–mediated cancer therapy. PMID:25837468

  9. Release and environmental impact of silver nanoparticles and conventional organic biocides from coated wooden façades.

    PubMed

    Künniger, Tina; Gerecke, Andreas C; Ulrich, Andrea; Huch, Anja; Vonbank, Roger; Heeb, Markus; Wichser, Adrian; Haag, Regula; Kunz, Petra; Faller, Markus

    2014-01-01

    This study represents for the first time a comprehensive assessment of functionality and environmental impacts of metallic silver nanoparticles (Ag-NP) compared to conventional organic biocides. Four different transparent, hydrophobic coatings of wooden outdoor façades were tested during one year outdoor weathering. The total silver release from products with Ag-NP was proportional to the overall erosion of the coating. The results indicate that the Ag-NPs are likely transformed to silver complexes, which are considerably less toxic than ionic silver. The protective effect of the silver containing coatings against mold, blue stain and algae was insufficient, even in immaculate and non-weathered conditions. The release of organic biocides from conventional coatings was dependent on the weather conditions, the type of biocide and the use in the base or top coat. The conventional coating showed a good overall performance free from mold, blue stain and algae until the end of the test period.

  10. Mucoadhesive polyethylenimine-dextran sulfate nanoparticles containing Punica granatum peel extract as a novel sustained-release antimicrobial.

    PubMed

    Tiyaboonchai, Waree; Rodleang, Ingdao; Ounaroon, Anan

    2015-06-01

    Mucoadhesive polyethylenimine-dextran sulfate nanoparticles (PDNPs) were developed for local oral mucosa delivery. Punica granatum peel extract (PGE) was loaded into PDNPs for oral malodor reduction and caries prevention. PDNPs were constructed using the polyelectrolyte complexation technique employing oppositely charged polymers polyethylenimine (PEI) and dextran sulfate (DS), with PEG 400 as a stabilizer. Under optimal conditions, spherical particles of ∼ 500 nm with a zeta potential of ∼+28 mV were produced. Up to 98%, drug entrapment efficiency was observed. The mass ratio of PEI:DS played a significant role in controlling particle size and entrapment efficacy. PDNPs shown to be a good mucoadhesive drug delivery system as confirmed by ex vivo wash off test. In vitro dissolution studies revealed that PGE-loaded PDNPs manifested a prolong release characteristic with a burst release within 5 min. In addition, they remained effectively against oral bacteria. PMID:24438035

  11. Isotonic sodium bicarbonate-triggered emodin release from borate stabilized emodin nanoparticles-loaded polymeric microgel films.

    PubMed

    Wang, Lin; Wang, Xiaohan; Li, Xiaozhou

    2014-07-20

    Hydrosoluble emodin-borate (EmB) nanoparticles (NPs) were fabricated by a simple solvent exchange method to address emodin's poor water solubility. As the result, negative charges were introduced in the surface of EmB NPs. In addition, layer-by-layer assembled multilayer films containing cation-rich polymeric microgels (named PAHD) and sodium carboxymethyl cellulose (NaCMC) were employed as drug carrier. Anionic EmB can be loaded into the PAHD/CMC multilayer films. The influences of various experimental parameters on cargo capacity of the PAHD/CMC film were studied in detail. The loaded EmB can be released in the form of emodin molecule in presence of isotonic sodium bicarbonate (ISB) solution. Gratifyingly, EmB did not almost release in presence of water, PBS buffer solution, 0.9% normal saline, and 5% glucose solution. PMID:24755249

  12. The fate of airborne nanoparticles released from a leak in a nanoparticle production process into a simulated workplace environment

    NASA Astrophysics Data System (ADS)

    Stanley, Nicholas James

    A leak in nanoparticle production equipment can cause large quantities of nanoparticles to be emitted into a workplace environment. Toxicity studies have shown hazards of inhaling nanoparticles; however these studies may not be using the proper particles. Physical and chemical changes may occur as these nanoparticles travel from the production site through ambient air, causing worker exposure. With the correct size and concentration known at distances from the leak, realistic worker exposure can be determined and appropriate worker protection and occupational monitoring schemes can be developed. Different nanoparticle materials were produced with a diffusion burner and injected through an experimentally simulated leak into a wind tunnel (simulated workplace environment). The wind tunnel background face velocity was 0.25 m/s. Soot distributions (dg = 59 and dg = 113 nm) and TiO2 (dg = 21 nm) were used as the test aerosols. A smaller distribution of particles (dg < 8 nm) was also noticed at the injection site for soot and TiO2. Lung deposited surface area concentration was measured using a NSAM and the number size distribution was measured with a SMPS at distances of 0.9 m, 1.8 m, and 3.4 m (times of 3.6 s, 7.2 s, and 13.6 s, respectively) from the injection point. TEM images were gathered at the injection point and 3.4 m downstream. The soot (dg = 113 nm) and TiO2 (dg = 21 nm) distributions produced loose, chain-type agglomerates at the injection point with primary particle sizes of dpp = 30 nm and dpp = 4.5 nm, respectively. These distributions experienced an increase in geometric mean particle size between the injection point and 0.9 m downstream. Surface area per particle (NSAM/SMPS ratio) also increased between the injection point and 0.9 m downstream. There was no additional particle change after 0.9 m. Primary particle size also increased after the injection point within the wind tunnel. Therefore the agglomerate size change may have been caused by the primary

  13. In situ DOX-calcium phosphate mineralized CPT-amphiphilic gelatin nanoparticle for intracellular controlled sequential release of multiple drugs.

    PubMed

    Li, Wei-Ming; Su, Chia-Wei; Chen, Yu-Wei; Chen, San-Yuan

    2015-03-01

    A co-delivery strategy has been developed to achieve the synergistic effect of a hydrophobic drug (camptothecin, CPT) and a hydrophilic drug (doxorubicin, DOX) by utilizing the unique structure of amphiphilic gelatin/camptothecin @calcium phosphate-doxorubicin (AG/CPT@CaP-DOX) nanoparticles as a carriers in order to replace double emulsions while preserving the advantages of inorganic materials. The hydrophobic agent (CPT) was encapsulated via emulsion with an amphiphilic gelatin core, and subsequently mineralized by CaP-hydrophilic drug (DOX) through precipitation to form a CaP shell on the CPT-AG amphiphilic gelatin core so that drug molecules with different characteristics (i.e. hydrophobic and hydrophilic) can be encapsulated in different regions to avoid their interaction. The existence of the CaP shell can protect the DOX against free release and cause an increased transfer of DOX across membranes, overcoming multidrug resistance. Release studies from core-shell carriers showed the possibility of achieving sequential release of more than one type of drug by controlling the pH-sensitive CaP shell and degradable AG core. The highly pH-responsive behavior of the carrier can modulate the dual-drug-release of DOX/CPT, specifically in acidic intracellular pH environments. The AG/CPT@CaP-DOX nanoparticles also exhibited higher drug efficiencies against MCF-7/ADR cells than MCF-7 cells, thanks to a synergistic cell cycle arrest/apoptosis-inducing effect between CPT and DOX. As such, this core-shell system can serve as a general platform for the localized, controlled, sequential delivery of multiple drugs to treat several diseases, especially for multidrug-resistant cancer cells.

  14. Fluorescent boronate-based polymer nanoparticles with reactive oxygen species (ROS)-triggered cargo release for drug-delivery applications

    NASA Astrophysics Data System (ADS)

    Jäger, Eliézer; Höcherl, Anita; Janoušková, Olga; Jäger, Alessandro; Hrubý, Martin; Konefał, Rafał; Netopilik, Miloš; Pánek, Jiří; Šlouf, Miroslav; Ulbrich, Karel; Štěpánek, Petr

    2016-03-01

    A new drug-delivery system of polymer nanoparticles (NPs) bearing pinacol-type boronic ester and alkyne moieties displaying triggered self-immolative polymer degradation in the presence of reactive oxygen species (ROS) with the capability of cellular imaging is presented. The NPs specifically release their drug cargo under concentrations of ROS that are commonly found in the intracellular environment of certain tumors and of inflamed tissues and exhibit significant cytotoxicity to cancer cells compared to their non-ROS-responsive counterparts.A new drug-delivery system of polymer nanoparticles (NPs) bearing pinacol-type boronic ester and alkyne moieties displaying triggered self-immolative polymer degradation in the presence of reactive oxygen species (ROS) with the capability of cellular imaging is presented. The NPs specifically release their drug cargo under concentrations of ROS that are commonly found in the intracellular environment of certain tumors and of inflamed tissues and exhibit significant cytotoxicity to cancer cells compared to their non-ROS-responsive counterparts. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr00791k

  15. Micro-organism-triggered release of silver nanoparticles from biodegradable oxide carriers allows preparation of self-sterilizing polymer surfaces.

    PubMed

    Loher, Stefan; Schneider, Oliver D; Maienfisch, Tobias; Bokorny, Stefan; Stark, Wendelin J

    2008-06-01

    The antimicrobial activity of silver has attracted significant research interest and contributes to an exponentially growing use of this noble metal in commodity products. In this investigation, we describe a general approach to increase the antimicrobial activity of a silver-containing surface by two to three orders of magnitude. The use of 1-2-nm silver particles decorating the surface of 20-50-nm carrier particles consisting of a phosphate-based, biodegradable ceramic allows the triggered release of silver in the presence of a growing microorganism. This effect is based on the organism's requirements for mineral uptake during growth creating a flux of calcium, phosphate, and other ions to the organism. The growing micro-organism dissolves the carrier containing these nutrients and thereby releases the silver nanoparticles. Further, we demonstrate the rapid self-sterilization of polymer surfaces containing silver on calcium phosphate nanoparticles using a series of human pathogens. Colony-forming units (viable bacteria or fungi counts) have been routinely reduced below detection limit and suggest application of these self-sterilizing surfaces in hospital environments, food and pharmaceutical processing, and personal care. PMID:18416429

  16. Silver release and antimicrobial properties of PMMA films doped with silver ions, nano-particles and complexes.

    PubMed

    Lyutakov, O; Goncharova, I; Rimpelova, S; Kolarova, K; Svanda, J; Svorcik, V

    2015-04-01

    Materials prepared on the base of bioactive silver compounds have become more and more popular due to low microbial resistance to silver. In the present work, the efficiency of polymethylmethacrylate (PMMA) thin films doped with silver ions, nanoparticles and silver-imidazole polymer complex was studied by a combination of AAS, XPS and AFM techniques. The biological activities of the proposed materials were discussed in view of the rate of silver releasing from the polymer matrix. Concentrations of Ag active form were estimated by its ability to interact with l-cysteine using electronic circular dichroism spectroscopy. Rates of the released silver were compared with the biological activity in dependence on the form of embedded silver. Antimicrobial properties of doped polymer films were studied using two bacterial strains: Staphylococcus epidermidis and Escherichia coli. It was found that PMMA films doped with Ag(+) had greater activity than those doped with nanoparticles and silver-imidazole polymeric complexes. However, the antimicrobial efficiency of Ag(+) doped films was only short-term. Contrary, the antimicrobial activity of silver-imidazole/PMMA films increased in time of sample soaking.

  17. Engineered peptides with enzymatically cleavable domains for controlling the release of model protein drug from "soft" nanoparticles.

    PubMed

    Singh, Harsh Deep; Bushnak, Ibraheem; Unsworth, Larry D

    2012-02-01

    Matrix metalloproteinase-2 (MMP-2) is an endopeptidase that has been shown to be present in high concentrations during most tissue remodeling events, including disease states like active tumor sites, thus making it an attractive molecule for use in effecting local delivery of therapeutic molecules. Moreover, the use of non-toxic and biodegradable nanoparticles for controlled drug delivery is highly sought after. To this end, bovine serum albumin (BSA) nanoparticles (NPs) were stabilized with coatings formed using domains of varying sensitivity to MMP-2, viz. K6GPQG/IASQK6 and K6HPVG/LLARK6, lysine residues being used to facilitate peptide immobilization to the BSA NPs via electrostatic interactions, and peptide domains that have a high (HPVG/LLAR) and low (GPQG/IASQ) MMP-2 cleavage rate. The MMP-2-induced cleavage rates of these two domains (the position of action being noted with a "/") have differing kinetics that can be used to provide a novel mechanism for facilitating the controlled release of molecules where local concentrations of MMP-2 are high. It was found that both surface concentration and cleavage domain type influenced the release of the model drug (BSA) from these NPs. This stratagem may provide a novel pathway for developing multi-functional coatings for controlling the local delivery of therapeutics at sites where the presence of various enzymes exist as a function of tissue state. PMID:22062019

  18. Micro-organism-triggered release of silver nanoparticles from biodegradable oxide carriers allows preparation of self-sterilizing polymer surfaces.

    PubMed

    Loher, Stefan; Schneider, Oliver D; Maienfisch, Tobias; Bokorny, Stefan; Stark, Wendelin J

    2008-06-01

    The antimicrobial activity of silver has attracted significant research interest and contributes to an exponentially growing use of this noble metal in commodity products. In this investigation, we describe a general approach to increase the antimicrobial activity of a silver-containing surface by two to three orders of magnitude. The use of 1-2-nm silver particles decorating the surface of 20-50-nm carrier particles consisting of a phosphate-based, biodegradable ceramic allows the triggered release of silver in the presence of a growing microorganism. This effect is based on the organism's requirements for mineral uptake during growth creating a flux of calcium, phosphate, and other ions to the organism. The growing micro-organism dissolves the carrier containing these nutrients and thereby releases the silver nanoparticles. Further, we demonstrate the rapid self-sterilization of polymer surfaces containing silver on calcium phosphate nanoparticles using a series of human pathogens. Colony-forming units (viable bacteria or fungi counts) have been routinely reduced below detection limit and suggest application of these self-sterilizing surfaces in hospital environments, food and pharmaceutical processing, and personal care.

  19. Sustained release of VEGF from PLGA nanoparticles embedded thermo-sensitive hydrogel in full-thickness porcine bladder acellular matrix

    PubMed Central

    2011-01-01

    We fabricated a novel vascular endothelial growth factor (VEGF)-loaded poly(lactic-co-glycolic acid) (PLGA)-nanoparticles (NPs)-embedded thermo-sensitive hydrogel in porcine bladder acellular matrix allograft (BAMA) system, which is designed for achieving a sustained release of VEGF protein, and embedding the protein carrier into the BAMA. We identified and optimized various formulations and process parameters to get the preferred particle size, entrapment, and polydispersibility of the VEGF-NPs, and incorporated the VEGF-NPs into the (poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (Pluronic®) F127 to achieve the preferred VEGF-NPs thermo-sensitive gel system. Then the thermal behavior of the system was proven by in vitro and in vivo study, and the kinetic-sustained release profile of the system embedded in porcine bladder acellular matrix was investigated. Results indicated that the bioactivity of the encapsulated VEGF released from the NPs was reserved, and the VEGF-NPs thermo-sensitive gel system can achieve sol-gel transmission successfully at appropriate temperature. Furthermore, the system can create a satisfactory tissue-compatible environment and an effective VEGF-sustained release approach. In conclusion, a novel VEGF-loaded PLGA NPs-embedded thermo-sensitive hydrogel in porcine BAMA system is successfully prepared, to provide a promising way for deficient bladder reconstruction therapy. PMID:21711840

  20. Potential risks of TiO2 and ZnO nanoparticles released from sunscreens into outdoor swimming pools.

    PubMed

    Jeon, Soo-Kyung; Kim, Eun-Ju; Lee, Jaesang; Lee, Seunghak

    2016-11-01

    The potential risks of nanoparticles (NPs) in sunscreens being released into swimming water were evaluated by a series of laboratory experiments simulating the fate and transport of NPs in outdoor swimming pools. NPs released from sunscreen-applied skin were estimated using pig skins covered with five different commercial sunscreens containing TiO2, ZnO, or both at various concentrations. Assuming that the swimming water treatment processes consisted of filtration, UV irradiation, heating, and chlorination, possible removal of the released NPs by each process was estimated. Generation of hydrogen peroxide (H2O2) by the NPs under sunlight and after UV photochemical treatment were measured, and the H2O2 concentration possibly present in the swimming pool was calculated based on some specific scenarios of operating an outdoor swimming pool. It was found that a significant amount of the NPs in sunscreens could be released into the swimming water, and accumulate during circulation through the treatment system. However, the concentration of H2O2 possibly present in the swimming pool should be below the level at which an adverse effect to bathers is concerned. PMID:27318727

  1. Release of phosphorous impurity from TiO2 anatase and rutile nanoparticles in aquatic environments and its implications.

    PubMed

    Liu, Xuyang; Chen, Gexin; Erwin, Justin G; Adam, Nadia K; Su, Chunming

    2013-10-15

    Phosphorus-bearing materials as an additive have been popularly used in nanomaterial synthesis and the residual phosphorus within the nanoparticles (NPs) can be of an environmental concern. For instance, phosphorus within pristine commercial TiO2 NPs greatly influences the surface charge and aggregation behavior of the host TiO2 in aquatic environments; however, it is unknown whether and how fast phosphorus is released. In this study, we focus on the phosphorus release kinetics from five types of TiO2 NPs (i.e., 5, 10, and 50 nm anatase and 10 × 40, 30 × 40 nm rutile) under the influence of varying solution chemistries. The 50 nm anatase has the highest quantity of P (8.05 g/kg) and most leachable P dissolves within the first 2 h (i.e., 5.01 g/kg), which presents a potential pollutant source of P. Higher pH favors the phosphorus release (release order: pH 11.2 > pH 8.2 > pH 2.4), while variations in the environmentally relevant ionic strengths (0.01 M NaCl + 0.01 M NaHCO3 and 0.04 M NaCl + 0.01 M NaHCO3) and the presence of dissolved natural organic matter (10 mg/L) do not affect release rate greatly. X-ray Absorption Near Edge Structure results suggest that phosphate adsorbed on the pristine 50 nm anatase desorbs, and some dissolved phosphate again re-sorbs as a surface precipitate. The findings from this research may have important environmental implications such as accidental release of TiO2 NPs and other nanomaterials that are synthesized using phosphorus containing chemicals as an ingredient.

  2. Sustained release of hydrophobic drugs by the microfluidic assembly of multistage microgel/poly (lactic-co-glycolic acid) nanoparticle composites

    PubMed Central

    Hsu, Myat Noe; Luo, Rongcong; Kwek, Kerwin Zeming; Por, Yong Chen; Zhang, Yong; Chen, Chia-Hung

    2015-01-01

    The poor solubility of many newly discovered drugs has resulted in numerous challenges for the time-controlled release of therapeutics. In this study, an advanced drug delivery platform to encapsulate and deliver hydrophobic drugs, consisting of poly (lactic-co-glycolic acid) (PLGA) nanoparticles incorporated within poly (ethylene glycol) (PEG) microgels, was developed. PLGA nanoparticles were used as the hydrophobic drug carrier, while the PEG matrix functioned to slow down the drug release. Encapsulation of the hydrophobic agents was characterized by fluorescence detection of the hydrophobic dye Nile Red within the microgels. In addition, the microcomposites prepared via the droplet-based microfluidic technology showed size tunability and a monodisperse size distribution, along with improved release kinetics of the loaded cargo compared with bare PLGA nanoparticles. This composite system has potential as a universal delivery platform for a variety of hydrophobic molecules. PMID:25825623

  3. Poly(N-isopropylacrylamide)-gated Fe3O4/SiO2 core shell nanoparticles with expanded mesoporous structures for the temperature triggered release of lysozyme.

    PubMed

    Yu, Erick; Galiana, Irene; Martínez-Máñez, Ramón; Stroeve, Pieter; Marcos, María D; Aznar, Elena; Sancenón, Félix; Murguía, José R; Amorós, Pedro

    2015-11-01

    Core-shell nanoparticles comprised of Fe3O4 cores and a mesoporous silica shell with an average expanded pore size of 6.07 nm and coated with a poly(N-isopropylacrylamide) (PNIPAM) layer (CS-MSNs-EP-PNIPAM) were prepared and characterized. The nanoparticles was loaded with (Ru(bipy)3(2+)) dye or an antibacterial enzyme, lysozyme, to obtain CS-MSNs-EP-PNIPAM-Ru(bipy)3(2+) and CS-MSNs-EP-PNIPAM-Lys, respectively. The lysozyme loading was determined to be 160 mg/g of nanoparticle. It was seen that Ru(bipy)3(2+) and lysozyme release was minimal at a room temperature of 25 °C while at physiological temperature (37 °C), abrupt release was observed. The applicability of the CS-MSNs-EP-PNIPAM-Lys was further tested with two Gram-positive bacteria samples, Bacillus cereus and Micrococcus luteus. At physiological temperature, the nanoparticles were shown to reduce bacterial growth, indicating a successful release of lysozyme from the nanoparticles. This nanoparticle system shows potential as a nanocarrier for the loading of similarly sized proteins or other species as a drug delivery platform. PMID:26335056

  4. Rapid-releasing of HI-6 via brain-targeted mesoporous silica nanoparticles for nerve agent detoxification

    NASA Astrophysics Data System (ADS)

    Yang, Jun; Fan, Lixue; Wang, Feijian; Luo, Yuan; Sui, Xin; Li, Wanhua; Zhang, Xiaohong; Wang, Yongan

    2016-05-01

    The toxic nerve agent (NA) soman is the most toxic artificially synthesized compound that can rapidly penetrate into the brain and irreversibly inhibit acetylcholinesterase (AChE) activity, leading to immediate death. However, there are currently few brain-targeted nanodrugs that can treat acute chemical brain poisoning owing to the limited drug-releasing speed. The present study investigated the effectiveness of a nanodrug against NA toxicity that has high blood-brain barrier penetration and is capable of rapid drug release. Transferrin-modified mesoporous silica nanoparticles (TF-MSNs) were conjugated with the known AChE reactivator HI-6. This nanodrug rapidly penetrated the blood-brain barrier in zebrafish and mice and restored cerebral AChE activity via the released HI-6, preventing the brain damage caused by soman poisoning and increasing the survival rate in mice. Furthermore, there was no toxicity associated with the MSNs in mice or rats. These results demonstrate that TF-MSNs loaded with HI-6 represent the most effective antidote against NA poisoning by soman reported to date, and suggest that MSNs are a safe alternative to conventional drugs and an optimal nanocarrier for treating brain poisoning, which requires acute pulse cerebral administration.The toxic nerve agent (NA) soman is the most toxic artificially synthesized compound that can rapidly penetrate into the brain and irreversibly inhibit acetylcholinesterase (AChE) activity, leading to immediate death. However, there are currently few brain-targeted nanodrugs that can treat acute chemical brain poisoning owing to the limited drug-releasing speed. The present study investigated the effectiveness of a nanodrug against NA toxicity that has high blood-brain barrier penetration and is capable of rapid drug release. Transferrin-modified mesoporous silica nanoparticles (TF-MSNs) were conjugated with the known AChE reactivator HI-6. This nanodrug rapidly penetrated the blood-brain barrier in zebrafish and

  5. Surface Changes and Impurity Release Kinetics of Titanium Dioxide Nanoparticles in Aqueous Environment

    EPA Science Inventory

    Previous studies have found the significant role of impurities (i.e., silicon, phosphorus) in the aggregation and sedimentation of TiO2 nanoparticles in water environment. However, it is not understood whether dissolution of the impurities potentially impacts the environment or t...

  6. Functionalized gold nanoparticle-polypyrrole nanobiocomposite with high effective surface area for electrochemical/pH dual stimuli-responsive smart release of insulin.

    PubMed

    Shamaeli, Ehsan; Alizadeh, Naader

    2015-02-01

    A novel functionalized gold nanoparticle-polypyrrole-nanobiocomposite (PPy-FGNP-NBC) with large effective surface area was fabricated for electrical/pH dual stimuli-responsive local delivery of insulin. The fabrication method involves simple electrodeposition and immobilization processes without use of organic solvents. Release studies based on the nature of insulin-surface binding indicated that release was promoted for PPy-FGNP-NBC. Kinetics analysis showed that release of insulin strongly affected by applying external potential stimuli. Also, the insulin release was under influence of pH and was slowed down under lower pH. This pH-sensitivity was remarkably increased by applying potential. Based on in vitro release study under applied potential condition, insulin release in the artificial gastric juice is significantly slower than that in the artificial intestinal fluid. Circular dichroism analysis showed that insulin retained its original conformation during electrochemically stimulated release.

  7. Rapid-releasing of HI-6 via brain-targeted mesoporous silica nanoparticles for nerve agent detoxification.

    PubMed

    Yang, Jun; Fan, Lixue; Wang, Feijian; Luo, Yuan; Sui, Xin; Li, Wanhua; Zhang, Xiaohong; Wang, Yongan

    2016-05-01

    The toxic nerve agent (NA) soman is the most toxic artificially synthesized compound that can rapidly penetrate into the brain and irreversibly inhibit acetylcholinesterase (AChE) activity, leading to immediate death. However, there are currently few brain-targeted nanodrugs that can treat acute chemical brain poisoning owing to the limited drug-releasing speed. The present study investigated the effectiveness of a nanodrug against NA toxicity that has high blood-brain barrier penetration and is capable of rapid drug release. Transferrin-modified mesoporous silica nanoparticles (TF-MSNs) were conjugated with the known AChE reactivator HI-6. This nanodrug rapidly penetrated the blood-brain barrier in zebrafish and mice and restored cerebral AChE activity via the released HI-6, preventing the brain damage caused by soman poisoning and increasing the survival rate in mice. Furthermore, there was no toxicity associated with the MSNs in mice or rats. These results demonstrate that TF-MSNs loaded with HI-6 represent the most effective antidote against NA poisoning by soman reported to date, and suggest that MSNs are a safe alternative to conventional drugs and an optimal nanocarrier for treating brain poisoning, which requires acute pulse cerebral administration.

  8. Silver nanoparticles temporarily retard NO2 - production without significantly affecting N2 O release by Nitrosomonas europaea.

    PubMed

    Michels, Camila; Yang, Yu; Moreira Soares, Hugo; Alvarez, Pedro J J

    2015-10-01

    Nitrifying bacteria are highly susceptible to silver nanoparticles (AgNPs). However, the effect of sublethal exposure to AgNPs after their release of nitrogenous compounds of environmental concern (e.g., the greenhouse gas nitrous oxide [N2 O] and the common water pollutant nitrite [NO2 -]) has not been systematically investigated. The present study reports the effect of AgNPs (and potentially released silver ions [Ag(+) ]) on NO2 - and N2 O production by Nitrosomonas europaea, and on the transcription of the associated genes. The release of NO2 - was more negatively affected than the production of N2 O. For example, exposure to AgNPs at 0.075 mg/L temporarily enhanced N2 O production (by 12%) without affecting nitrite release, whereas higher AgNP concentrations (>0.25 mg/L) inhibited NO2 - release (by >12%) but not N2 O production. Transcriptomic analyses corroborated these trends; AgNPs at 0.075 mg/L increased the expression of the nitric oxide reductase gene (norQ) associated with N2 O production (by 5.3-fold to 12.8-fold), whereas both 0.075 mg/L of Ag(+) and 0.75 mg/L of AgNPs down-regulated the ammonia monooxygenase gene (amoA2; by 0.08-fold to 0.15-fold and 0.32-fold to 0.64-fold, respectively), the nitrite reductase gene (nirK; by 0.01-fold to 0.02-fold and 0.22-fold to 0.44-fold, respectively), and norQ (by 0.11-fold to 0.15-fold and 0.32-fold to 0.57-fold, respectively). These results suggest that AgNP release to sewage treatment plants and land application of AgNP-containing biosolids should be minimized because of their potential temporary stimulation of N2 O release and interference with nitrification. Environ Toxicol Chem 2015;34:2231-2235. © 2015 SETAC. PMID:26010547

  9. Hydrophobic ion pairing of a minocycline/Ca(2+)/AOT complex for preparation of drug-loaded PLGA nanoparticles with improved sustained release.

    PubMed

    Holmkvist, Alexander Dontsios; Friberg, Annika; Nilsson, Ulf J; Schouenborg, Jens

    2016-02-29

    Polymeric nanoparticles is an established and efficient means to achieve controlled release of drugs. Incorporation of minocycline, an antibiotic with anti-inflammatory and neuroprotective properties, into biodegradable nanoparticles may therefore provide an efficient means to combat foreign body reactions to implanted electrodes in the brain. However, minocycline is commonly associated with poor encapsulation efficiencies and/or fast release rates due to its high solubility in water. Moreover, minocycline is unstable under conditions of low and high pH, heat and exposure to light, which exacerbate the challenges of encapsulation. In this work drug loaded PLGA nanoparticles were prepared by a modified emulsification-solvent-diffusion technique and characterized for size, drug encapsulation and in vitro drug release. A novel hydrophobic ion pair complex of minocycline, Ca(2+) ions and the anionic surfactant AOT was developed to protect minocycline from degradation and prolong its release. The optimized formulation resulted in particle sizes around 220 nm with an entrapment efficiency of 43% and showed drug release over 30 days in artificial cerebrospinal fluid. The present results constitute a substantial increase in release time compared to what has hitherto been achieved for minocycline and indicate that such particles might provide useful for sustained drug delivery in the CNS. PMID:26773599

  10. Hydration kinetics, ion-release and antimicrobial properties of white Portland cement blended with zirconium oxide nanoparticles.

    PubMed

    Li, Qiu; Coleman, Nichola J

    2014-01-01

    This study examines the impact of 20 wt% zirconium oxide nanoparticles on the early hydration kinetics of white Portland cement by isothermal conduction calorimetry and transmission electron microscopy. The findings confirm that the nano-ZrO2 particles do not directly participate in the chemical reactions during cement hydration; although, they do divert the normal hydration processes and accelerate the initial setting reactions. The rate of heat evolution and the extent of the exotherm associated with these reactions are reduced in the presence of nano-ZrO2. The incorporation of nano-ZrO2 into the cement also decreases the solubility of the silicate phases but does not compromise its capacity to release hydroxide ions. There was no observed difference in the antimicrobial activity of the nano-ZrO2-blended and unblended cement pastes against S. aureus and E. coli; however, a modest reduction in this property was noted against P. aeruginosa for the blended cement.

  11. Bioinspired fluorescent dipeptide nanoparticles for targeted cancer cell imaging and real-time monitoring of drug release

    NASA Astrophysics Data System (ADS)

    Fan, Zhen; Sun, Leming; Huang, Yujian; Wang, Yongzhong; Zhang, Mingjun

    2016-04-01

    Peptide nanostructures are biodegradable and are suitable for many biomedical applications. However, to be useful imaging probes, the limited intrinsic optical properties of peptides must be overcome. Here we show the formation of tryptophan–phenylalanine dipeptide nanoparticles (DNPs) that can shift the peptide's intrinsic fluorescent signal from the ultraviolet to the visible range. The visible emission signal allows the DNPs to act as imaging and sensing probes. The peptide design is inspired by the red shift seen in the yellow fluorescent protein that results from π–π stacking and by the enhanced fluorescence intensity seen in the green fluorescent protein mutant, BFPms1, which results from the structure rigidification by Zn(II). We show that DNPs are photostable, biocompatible and have a narrow emission bandwidth and visible fluorescence properties. DNPs functionalized with the MUC1 aptamer and doxorubicin can target cancer cells and can be used to image and monitor drug release in real time.

  12. Bioinspired fluorescent dipeptide nanoparticles for targeted cancer cell imaging and real-time monitoring of drug release

    NASA Astrophysics Data System (ADS)

    Fan, Zhen; Sun, Leming; Huang, Yujian; Wang, Yongzhong; Zhang, Mingjun

    2016-04-01

    Peptide nanostructures are biodegradable and are suitable for many biomedical applications. However, to be useful imaging probes, the limited intrinsic optical properties of peptides must be overcome. Here we show the formation of tryptophan-phenylalanine dipeptide nanoparticles (DNPs) that can shift the peptide's intrinsic fluorescent signal from the ultraviolet to the visible range. The visible emission signal allows the DNPs to act as imaging and sensing probes. The peptide design is inspired by the red shift seen in the yellow fluorescent protein that results from π-π stacking and by the enhanced fluorescence intensity seen in the green fluorescent protein mutant, BFPms1, which results from the structure rigidification by Zn(II). We show that DNPs are photostable, biocompatible and have a narrow emission bandwidth and visible fluorescence properties. DNPs functionalized with the MUC1 aptamer and doxorubicin can target cancer cells and can be used to image and monitor drug release in real time.

  13. Genetically designed biomolecular capping system for mesoporous silica nanoparticles enables receptor-mediated cell uptake and controlled drug release

    NASA Astrophysics Data System (ADS)

    Datz, Stefan; Argyo, Christian; Gattner, Michael; Weiss, Veronika; Brunner, Korbinian; Bretzler, Johanna; von Schirnding, Constantin; Torrano, Adriano A.; Spada, Fabio; Vrabel, Milan; Engelke, Hanna; Bräuchle, Christoph; Carell, Thomas; Bein, Thomas

    2016-04-01

    Effective and controlled drug delivery systems with on-demand release and targeting abilities have received enormous attention for biomedical applications. Here, we describe a novel enzyme-based cap system for mesoporous silica nanoparticles (MSNs) that is directly combined with a targeting ligand via bio-orthogonal click chemistry. The capping system is based on the pH-responsive binding of an aryl-sulfonamide-functionalized MSN and the enzyme carbonic anhydrase (CA). An unnatural amino acid (UAA) containing a norbornene moiety was genetically incorporated into CA. This UAA allowed for the site-specific bio-orthogonal attachment of even very sensitive targeting ligands such as folic acid and anandamide. This leads to specific receptor-mediated cell and stem cell uptake. We demonstrate the successful delivery and release of the chemotherapeutic agent Actinomycin D to KB cells. This novel nanocarrier concept provides a promising platform for the development of precisely controllable and highly modular theranostic systems.Effective and controlled drug delivery systems with on-demand release and targeting abilities have received enormous attention for biomedical applications. Here, we describe a novel enzyme-based cap system for mesoporous silica nanoparticles (MSNs) that is directly combined with a targeting ligand via bio-orthogonal click chemistry. The capping system is based on the pH-responsive binding of an aryl-sulfonamide-functionalized MSN and the enzyme carbonic anhydrase (CA). An unnatural amino acid (UAA) containing a norbornene moiety was genetically incorporated into CA. This UAA allowed for the site-specific bio-orthogonal attachment of even very sensitive targeting ligands such as folic acid and anandamide. This leads to specific receptor-mediated cell and stem cell uptake. We demonstrate the successful delivery and release of the chemotherapeutic agent Actinomycin D to KB cells. This novel nanocarrier concept provides a promising platform for the

  14. Evaluation of metal oxide and carbonate nanoparticle stability in soybean oil: Implications for controlled release of alkalinity during subsurface remediation

    NASA Astrophysics Data System (ADS)

    Ramsburg, C. A.; Leach, O. I.; Sebik, J.; Muller, K.

    2011-12-01

    Traditional methods for adjusting groundwater pH rely on injection of aqueous solutes and therefore, amendment distribution is reliant upon aqueous phase flow and transport. This reliance can limit mixing and sustention of amendments within the treatment zone. Oil-in-water emulsions offer an alternative for amendment delivery - one that has potential to enhance control of the distribution and release of buffering agents within the subsurface. Focus here is placed on using metal oxide and carbonate nanoparticles to release alkalinity from soybean oil, a common dispersed phase within emulsions designed to support remediation activities. Batch reactor systems were employed to examine the influence of dispersed phase composition on particle stability and solubility. The stability of uncoated MgO and CaCO3 particles in unmodified soybean oil was explored in a series of sedimentation studies conducted at solid loadings of 0.05, 0.1, and 0.2% mass. Three nominal sizes of MgO particles were examined (20, 50, and 100 nm) and one CaCO3 particle size (60 nm). Results from sedimentation studies conducted over four hours suggest that the viscosity of the soybean oil imparts a kinetic stability, for all sizes of the uncoated MgO and CaCO3 nanoparticles, which is sufficient time for particle encapsulation within oil-in-water emulsions. Based upon these results, the sedimentation of the 50 nm and 100 nm MgO, and 60 nm CaCO3 particles was assessed over longer durations (≥72 hr). Results from these stability tests suggest that the 50 nm and 100 nm MgO particles have greater kinetic stability than the 60 nm CaCO3. Batch studies were also used to assess the influence of n-butanol, a co-solvent hypothesized to aid in controlling the rate of alkalinity release, on phase behavior and metal (Mg2+ and Ca2+) solubility. Phase behavior studies suggest that n-butanol has a limited region of miscibility within the soybean oil-water system. Use of n-butanol and water within this region of

  15. Existence, release, and antibacterial actions of silver nanoparticles on Ag–PIII TiO2 films with different nanotopographies

    PubMed Central

    Li, Jinhua; Qiao, Yuqin; Zhu, Hongqin; Meng, Fanhao; Liu, Xuanyong

    2014-01-01

    Nanotopographical TiO2 films (including nanorod, nanotip, and nanowire topographies) were successfully fabricated on the metallic Ti surface via hydrothermal treatment and then underwent Ag plasma immersion ion implantation to incorporate Ag with TiO2. The surface morphology, phase component, and chemical composition before and after Ag–PIII were characterized. In view of the potential clinical applications, both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus were used to estimate their antimicrobial effect. The nanostructured TiO2 films on a Ti surface exhibit a better bacteriostatic effect on both microbes compared to the pristine Ti. The nanotopographies of the TiO2 films affect the nucleation, growth, and distribution of Ag nanoparticles in the films during Ag–PIII process. The Ag nanoparticles are completely embedded into the nanorod film while partially exposed out of the nanotip and nanowire films, which account for the significant differences in the release behaviors of Ag ions in vitro. However, no significant difference exists in their antimicrobial activity against both microbes. The antimicrobial actions of the Ag@TiO2 system described here consist of two methods – the contact-killing action and the release-killing action. Nevertheless, based on the observed results, the contact-killing action should be regarded as the main method to destroy microbes for all the Ag plasma-modified TiO2 nanofilms. This study provides insight to optimize the surface design of Ti-based implants to acquire more effective antimicrobial surfaces to meet clinical applications. PMID:25075186

  16. Multilayer Coating of Tetrandrine-loaded PLGA nanoparticles: Effect of surface charges on cellular uptake rate and drug release profile.

    PubMed

    Meng, Rui; Li, Ke; Chen, Zhe; Shi, Chen

    2016-02-01

    The effect of surface charges on the cellular uptake rate and drug release profile of tetrandrine-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (TPNs) was studied. Stabilizer-free nanoprecipitation method was used in this study for the synthesis of TPNs. A typical layer-by-layer approach was applied for multi-coating particles' surface with use of poly(styrene sulfonate) sodium salt (PSS) as anionic layer and poly(allylamine hydrochloride) (PAH) as cationic layer. The modified TPNs were characterized by different physicochemical techniques such as Zeta sizer, scanning electron microscopy and transmission electron microscopy. The drug loading efficiency, release profile and cellular uptake rate were evaluated by high performance liquid chromatography and confocal laser scanning microscopy, respectively. The resultant PSS/PAH/PSS/PAH/TPNs (4 layers) exhibited spherical-shaped morphology with the average size of 160.3±5.165 nm and zeta potential of-57.8 mV. The encapsulation efficiency and drug loading efficiency were 57.88% and 1.73%, respectively. Multi-layer coating of polymeric materials with different charges on particles' surface could dramatically influence the drug release profile of TPNs (4 layers vs. 3 layers). In addition, variable layers of surface coating could also greatly affect the cellular uptake rate of TPNs in A549 cells within 8 h. Overall, by coating particles' surface with those different charged polymers, precise control of drug release as well as cellular uptake rate can be achieved simultaneously. Thus, this approach provides a new strategy for controllable drug delivery. PMID:26838734

  17. A new method for pH triggered curcumin release by applying poly(L-lysine) mediated nanoparticle-congregation.

    PubMed

    Patra, Digambara; Sleem, Fatima

    2013-09-17

    We introduce a novel method for encapsulation of curcumin by synthesizing microcapsule containing self-assembled nanoparticles using poly (L-lysine), trisodium citrate and silica sol. Such microcapsules can only be prepared in neutral and alkaline environment and unencapsulated curcumin can be effectively removed by simple centrifugation with encapsulation efficiency 57.34%. The particle sizes are in the range 0.7-3 μm with an effective diameter 1.05 μm. The structure of the microcapsules is dependent upon the solubility of curcumin in the solvent environment, the microcapsule are spherical when prepared in 10% acetone and bowl-shaped/conical when prepared in water suspension, however, the size of these curcumin encapsulated microcapsules remain similar. Fluorescence microscope images confirm that curcumin is predominantly concentrated within the shell wall of the capsules. Photophysical behavior of Micro-curcumin with respect to curcumin alone is evaluated. Release of curcumin is found to be triggered by pH where acidic environment trigger maximum release compared to basic and neutral conditions. Micro-curcumin is as stable as curcumin. Drug release efficiency is found to be 61.44% and the drug release profile of Micro-curcumin follow Higuchi model. It is also revealed that β-diketone group of curcumin responsible for scavenging activity is retained in the Micro-curcumin, thus suggesting applicability of such system as a poorly water soluble drug delivery vehicle. In contrast to other curcumin delivery systems, the presented method is easy, fast and does not need flow rate monitoring device. In addition poly (L-lysine) as a non-toxic and highly stable material that prevents metabolic degradation is used in the present preparation method. PMID:23998538

  18. A Controlled Release Codelivery System of MSCs Encapsulated in Dextran/Gelatin Hydrogel with TGF-β3-Loaded Nanoparticles for Nucleus Pulposus Regeneration

    PubMed Central

    Xu, Yuan; Luo, Xiangdong

    2016-01-01

    Mesenchymal stem cell- (MSC-) based therapy is regarded as a potential tissue engineering strategy to achieve nucleus pulposus (NP) regeneration for the treatment of intervertebral disc degeneration (IDD). However, it is still a challenge to induce MSC differentiation in NP-like cells when MSCs are implanted into the NP. The purpose of this study was to construct poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles as carriers for TGF-β3 controlled release and establish a codelivery system of a dextran/gelatin hydrogel with the nanoparticles for long-term processing of discogenesis differentiation. TGF-β3-loaded PLGA nanoparticles were prepared by the double-emulsion solvent evaporation method and seeded uniformly into the hydrogel. Morphological observations, an assessment of the release kinetics of TGF-β3, a cytotoxic assay, a cell proliferation test, a biochemical content assay, qRT-PCR, and immunohistological analyses of the codelivery system were conducted in the study. The results showed that the TGF-β3-loaded nanoparticles could release TGF-β3 gradually. The codelivery system exhibited favorable cytocompatibility, and the TGF-β3 that was released could induce MSCs to NP-like cells while promoting ECM-related biosynthesis. These results suggest this codelivery system may be employed as a promising carrier for discogenesis of MSCs in situ. PMID:27774108

  19. Formation and characterization of β-cyclodextrin (β-CD) - polyethyleneglycol (PEG) - polyethyleneimine (PEI) coated Fe3O4 nanoparticles for loading and releasing 5-Fluorouracil drug.

    PubMed

    Prabha, G; Raj, V

    2016-05-01

    In this work, β-cyclodextrin (β-CD) - polyethyleneglycol (PEG) - polyethyleneimine (PEI) coated iron oxide nanoparticles (Fe3O4-β-CD-PEG-PEI) were developed as drug carriers for drug delivery applications. The 5- Fluorouracil (5-FU) was chosen as model drug molecule. The developed nanoparticles (Fe3O4-β-CD-PEG-PEI) were characterized by various techniques such as Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), Scanning electron microscopy (SEM), transmission electron microscopy (TEM) and vibrating sample magnetometry (VSM). The average particles size range of 5-FU loaded Fe3O4-β-CD, Fe3O4-β-CD-PEG and Fe3O4-β-CD-PEG-PEI nanoparticles were from 151 to 300nm and zeta potential value of nanoparticles were from -43mV to -20mV as measured using Malvern Zetasizer. Finally, encapsulation efficiency (EE), loading capacity (LC) and in-vitro drug release performance of 5-FU drug loaded Fe3O4-β-CD, Fe3O4-β-CD-PEG and Fe3O4-β-CD-PEG-PEI nanoparticles was evaluated by UV-vis spectroscopy. In-vitro cytotoxicity tests investigated by MTT assay indicate that 5-FU loaded Fe3O4-β-CD-PEG-PEI nanoparticles were toxic to cancer cells and non-toxic to normal cells. The in-vitro release behavior of 5-FU from drug (5-FU) loaded Fe3O4-β-CD-PEG-PEI composite at different pH values and temperature was studied. It was found that 5-FU was released faster in pH 6.8 than in the acidic mediums (pH 1.2), and the released quantity was higher. Therefore, the newly prepared Fe3O4-β-CD-PEG-PEI carrier exhibits a promising potential capability for anticancer drug delivery in tumor therapy. PMID:27133054

  20. Formation and characterization of β-cyclodextrin (β-CD) - polyethyleneglycol (PEG) - polyethyleneimine (PEI) coated Fe3O4 nanoparticles for loading and releasing 5-Fluorouracil drug.

    PubMed

    Prabha, G; Raj, V

    2016-05-01

    In this work, β-cyclodextrin (β-CD) - polyethyleneglycol (PEG) - polyethyleneimine (PEI) coated iron oxide nanoparticles (Fe3O4-β-CD-PEG-PEI) were developed as drug carriers for drug delivery applications. The 5- Fluorouracil (5-FU) was chosen as model drug molecule. The developed nanoparticles (Fe3O4-β-CD-PEG-PEI) were characterized by various techniques such as Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), Scanning electron microscopy (SEM), transmission electron microscopy (TEM) and vibrating sample magnetometry (VSM). The average particles size range of 5-FU loaded Fe3O4-β-CD, Fe3O4-β-CD-PEG and Fe3O4-β-CD-PEG-PEI nanoparticles were from 151 to 300nm and zeta potential value of nanoparticles were from -43mV to -20mV as measured using Malvern Zetasizer. Finally, encapsulation efficiency (EE), loading capacity (LC) and in-vitro drug release performance of 5-FU drug loaded Fe3O4-β-CD, Fe3O4-β-CD-PEG and Fe3O4-β-CD-PEG-PEI nanoparticles was evaluated by UV-vis spectroscopy. In-vitro cytotoxicity tests investigated by MTT assay indicate that 5-FU loaded Fe3O4-β-CD-PEG-PEI nanoparticles were toxic to cancer cells and non-toxic to normal cells. The in-vitro release behavior of 5-FU from drug (5-FU) loaded Fe3O4-β-CD-PEG-PEI composite at different pH values and temperature was studied. It was found that 5-FU was released faster in pH 6.8 than in the acidic mediums (pH 1.2), and the released quantity was higher. Therefore, the newly prepared Fe3O4-β-CD-PEG-PEI carrier exhibits a promising potential capability for anticancer drug delivery in tumor therapy.

  1. Size-dependent cytotoxicity of silver nanoparticles in human lung cells: the role of cellular uptake, agglomeration and Ag release

    PubMed Central

    2014-01-01

    Background Silver nanoparticles (AgNPs) are currently one of the most manufactured nanomaterials. A wide range of toxicity studies have been performed on various AgNPs, but these studies report a high variation in toxicity and often lack proper particle characterization. The aim of this study was to investigate size- and coating-dependent toxicity of thoroughly characterized AgNPs following exposure of human lung cells and to explore the mechanisms of toxicity. Methods BEAS-2B cells were exposed to citrate coated AgNPs of different primary particle sizes (10, 40 and 75 nm) as well as to 10 nm PVP coated and 50 nm uncoated AgNPs. The particle agglomeration in cell medium was investigated by photon cross correlation spectroscopy (PCCS); cell viability by LDH and Alamar Blue assay; ROS induction by DCFH-DA assay; genotoxicity by alkaline comet assay and γH2AX foci formation; uptake and intracellular localization by transmission electron microscopy (TEM); and cellular dose as well as Ag release by atomic absorption spectroscopy (AAS). Results The results showed cytotoxicity only of the 10 nm particles independent of surface coating. In contrast, all AgNPs tested caused an increase in overall DNA damage after 24 h assessed by the comet assay, suggesting independent mechanisms for cytotoxicity and DNA damage. However, there was no γH2AX foci formation and no increased production of intracellular reactive oxygen species (ROS). The reasons for the higher toxicity of the 10 nm particles were explored by investigating particle agglomeration in cell medium, cellular uptake, intracellular localization and Ag release. Despite different agglomeration patterns, there was no evident difference in the uptake or intracellular localization of the citrate and PVP coated AgNPs. However, the 10 nm particles released significantly more Ag compared with all other AgNPs (approx. 24 wt% vs. 4–7 wt%) following 24 h in cell medium. The released fraction in cell medium did not induce any

  2. Controlled-release of tetracycline and lovastatin by poly(D,L-lactide-co-glycolide acid)-chitosan nanoparticles enhances periodontal regeneration in dogs.

    PubMed

    Lee, Bor-Shiunn; Lee, Chien-Chen; Wang, Yi-Ping; Chen, Hsiao-Jan; Lai, Chern-Hsiung; Hsieh, Wan-Ling; Chen, Yi-Wen

    2016-01-01

    Chronic periodontitis is characterized by inflammation of periodontal tissues, leading to bone resorption and tooth loss. The goal of treatment is to regenerate periodontal tissues including bone and cementum lost as a consequence of disease. The local delivery of tetracycline was proven to be effective in controlling localized periodontal infection without apparent side effects. Previous studies suggested that lovastatin has a significant role in new bone formation; however, the local delivery of lovastatin might enhance its therapeutic effects. A number of local delivery devices have been developed recently, including poly(D,L-lactide-co-glycolide acid) (PLGA) nanoparticles. The aim of this study was to develop a local delivery device, PLGA-lovastatin-chitosan-tetracycline nanoparticles, which allows the sequential release of tetracycline and lovastatin to effectively control local infection and promote bone regeneration in periodontitis. The size and microstructure of nanoparticles were examined by transmission electron microscopy, Nanoparticle Size Analyzer, and Fourier transform infrared spectroscopy. The release of tetracycline and lovastatin was quantified using a UV-Vis spectrophotometer. Furthermore, the cytotoxic effect and alkaline phosphatase activity of the nanoparticles in osteoblast cell cultures as well as antibacterial activity against periodontal pathogens were investigated. Finally, the bone regeneration potential of PLGA nanoparticles in three-walled defects in beagle dogs was investigated. The results indicated that PLGA-lovastatin-chitosan-tetracycline nanoparticles showed good biocompatibility, antibacterial activity, and increased alkaline phosphatase activity. The volumetric analysis from micro-CT revealed significantly increased new bone formation in defects filled with nanoparticles in dogs. This novel local delivery device might be useful as an adjunctive treatment in periodontal regenerative therapy.

  3. Controlled-release of tetracycline and lovastatin by poly(d,l-lactide-co-glycolide acid)-chitosan nanoparticles enhances periodontal regeneration in dogs

    PubMed Central

    Lee, Bor-Shiunn; Lee, Chien-Chen; Wang, Yi-Ping; Chen, Hsiao-Jan; Lai, Chern-Hsiung; Hsieh, Wan-Ling; Chen, Yi-Wen

    2016-01-01

    Chronic periodontitis is characterized by inflammation of periodontal tissues, leading to bone resorption and tooth loss. The goal of treatment is to regenerate periodontal tissues including bone and cementum lost as a consequence of disease. The local delivery of tetracycline was proven to be effective in controlling localized periodontal infection without apparent side effects. Previous studies suggested that lovastatin has a significant role in new bone formation; however, the local delivery of lovastatin might enhance its therapeutic effects. A number of local delivery devices have been developed recently, including poly(d,l-lactide-co-glycolide acid) (PLGA) nanoparticles. The aim of this study was to develop a local delivery device, PLGA-lovastatin-chitosan-tetracycline nanoparticles, which allows the sequential release of tetracycline and lovastatin to effectively control local infection and promote bone regeneration in periodontitis. The size and microstructure of nanoparticles were examined by transmission electron microscopy, Nanoparticle Size Analyzer, and Fourier transform infrared spectroscopy. The release of tetracycline and lovastatin was quantified using a UV-Vis spectrophotometer. Furthermore, the cytotoxic effect and alkaline phosphatase activity of the nanoparticles in osteoblast cell cultures as well as antibacterial activity against periodontal pathogens were investigated. Finally, the bone regeneration potential of PLGA nanoparticles in three-walled defects in beagle dogs was investigated. The results indicated that PLGA-lovastatin-chitosan-tetracycline nanoparticles showed good biocompatibility, antibacterial activity, and increased alkaline phosphatase activity. The volumetric analysis from micro-CT revealed significantly increased new bone formation in defects filled with nanoparticles in dogs. This novel local delivery device might be useful as an adjunctive treatment in periodontal regenerative therapy. PMID:26848264

  4. Controlled-release of tetracycline and lovastatin by poly(D,L-lactide-co-glycolide acid)-chitosan nanoparticles enhances periodontal regeneration in dogs.

    PubMed

    Lee, Bor-Shiunn; Lee, Chien-Chen; Wang, Yi-Ping; Chen, Hsiao-Jan; Lai, Chern-Hsiung; Hsieh, Wan-Ling; Chen, Yi-Wen

    2016-01-01

    Chronic periodontitis is characterized by inflammation of periodontal tissues, leading to bone resorption and tooth loss. The goal of treatment is to regenerate periodontal tissues including bone and cementum lost as a consequence of disease. The local delivery of tetracycline was proven to be effective in controlling localized periodontal infection without apparent side effects. Previous studies suggested that lovastatin has a significant role in new bone formation; however, the local delivery of lovastatin might enhance its therapeutic effects. A number of local delivery devices have been developed recently, including poly(D,L-lactide-co-glycolide acid) (PLGA) nanoparticles. The aim of this study was to develop a local delivery device, PLGA-lovastatin-chitosan-tetracycline nanoparticles, which allows the sequential release of tetracycline and lovastatin to effectively control local infection and promote bone regeneration in periodontitis. The size and microstructure of nanoparticles were examined by transmission electron microscopy, Nanoparticle Size Analyzer, and Fourier transform infrared spectroscopy. The release of tetracycline and lovastatin was quantified using a UV-Vis spectrophotometer. Furthermore, the cytotoxic effect and alkaline phosphatase activity of the nanoparticles in osteoblast cell cultures as well as antibacterial activity against periodontal pathogens were investigated. Finally, the bone regeneration potential of PLGA nanoparticles in three-walled defects in beagle dogs was investigated. The results indicated that PLGA-lovastatin-chitosan-tetracycline nanoparticles showed good biocompatibility, antibacterial activity, and increased alkaline phosphatase activity. The volumetric analysis from micro-CT revealed significantly increased new bone formation in defects filled with nanoparticles in dogs. This novel local delivery device might be useful as an adjunctive treatment in periodontal regenerative therapy. PMID:26848264

  5. A stimuli-responsive nanoparticulate system using poly(ethylenimine)-graft-polysorbate for controlled protein release.

    PubMed

    Lai, Wing-Fu; Shum, Ho Cheung

    2016-01-01

    Proteins have emerged as an important class of therapeutic agents due to their high specificity in their physiological actions. Over the years, diverse protein carriers have been developed; however, some concerns, such as the relatively low loading efficiency and release sustainability, have limited the efficiency of protein delivery. This study reports the use of hydrogel nanoparticles based on a novel copolymer, poly(ethylenimine)-graft-polysorbate (PEIP), as effective protein carriers. The copolymer is fabricated by grafting poly(ethylenimine) (PEI) with polysorbate 20 using carbonyldiimidazole chemistry. Its cytotoxicity is much lower than that of unmodified PEI in RGC5 and HEK293 cells. In comparison with nanoparticles formed by unmodified PEI, our nanoparticles are not only more efficient in cellular internalization, as indicated by the 5- to 6-fold reduction in the time they take to cause 90% of cells to exhibit intracellular fluorescence, but also give a protein loading efficiency as high as 70-90%. These, together with the salt-responsiveness of the nanoparticles in protein release and the retention of the activity of the loaded protein, suggest that PEIP and its hydrogel nanoparticles warrant further development as protein carriers for therapeutic applications. PMID:26676890

  6. A stimuli-responsive nanoparticulate system using poly(ethylenimine)-graft-polysorbate for controlled protein release

    NASA Astrophysics Data System (ADS)

    Lai, Wing-Fu; Shum, Ho Cheung

    2015-12-01

    Proteins have emerged as an important class of therapeutic agents due to their high specificity in their physiological actions. Over the years, diverse protein carriers have been developed; however, some concerns, such as the relatively low loading efficiency and release sustainability, have limited the efficiency of protein delivery. This study reports the use of hydrogel nanoparticles based on a novel copolymer, poly(ethylenimine)-graft-polysorbate (PEIP), as effective protein carriers. The copolymer is fabricated by grafting poly(ethylenimine) (PEI) with polysorbate 20 using carbonyldiimidazole chemistry. Its cytotoxicity is much lower than that of unmodified PEI in RGC5 and HEK293 cells. In comparison with nanoparticles formed by unmodified PEI, our nanoparticles are not only more efficient in cellular internalization, as indicated by the 5- to 6-fold reduction in the time they take to cause 90% of cells to exhibit intracellular fluorescence, but also give a protein loading efficiency as high as 70-90%. These, together with the salt-responsiveness of the nanoparticles in protein release and the retention of the activity of the loaded protein, suggest that PEIP and its hydrogel nanoparticles warrant further development as protein carriers for therapeutic applications.

  7. Effect of soluble copper released from copper oxide nanoparticles solubilisation on growth and photosynthetic processes of Lemna gibba L.

    PubMed

    Perreault, François; Samadani, Mahshid; Dewez, David

    2014-06-01

    Copper oxide nanoparticles (CuO NPs) are used as a biocide in paints, textiles and plastics. Their application may lead to the contamination of aquatic ecosystems, where potential environmental effects remain to be determined. Toxic effects may be related to interactions of NPs with cellular systems or to particles' solubilisation releasing metal ions. In this report, we evaluated CuO NPs and soluble copper effects on photosynthesis of the aquatic macrophyte Lemna gibba L to determine the role of particle solubility in NPs toxicity. When L. gibba plants were exposed 48 h to CuO NPs or soluble copper, inhibition of photosynthetic activity was found, indicated by the inactivation of Photosystem II reaction centers, a decrease in electron transport and an increase of thermal energy dissipation. Toxicity of CuO NPs was mainly driven by copper ions released from particles. However, the bioaccumulation of CuO NPs in plant was shown, indicating the need to evaluate organisms of higher trophic level.

  8. Cationic solid lipid nanoparticles with primary and quaternary amines for release of saquinavir and biocompatibility with endothelia.

    PubMed

    Kuo, Yung-Chih; Wang, Cheng-Chin

    2013-01-01

    Application of cationic solid lipid nanoparticles (CSLNs), comprising complex internal matrix and lipid-regulated external surface, is an intriguing issue in current bionanotechnology. This study presents dissolution kinetics of saquinavir (SQV) from CSLNs with cholesterol-mediated esterquat 1 (EQ 1) and biocompatibility of SQV-loaded CSLNs with human brain-microvascular endothelial cells (HBMECs). CSLNs with SQV in lipid cores containing cholesterol were dissolved and incubated with HBMECs. The results revealed that an increase in the weight percentage of EQ 1 reduced the entrapment efficiency of SQV. In addition, the entrapment efficiency of SQV enhanced, when the weight percentage of cholesterol increased from 0% to 25% (w/w). The reverse was true when cholesterol increased from 0% to 75% (w/w). The dissolution profiles demonstrated that the mediation of cholesterol favored the sustained release of SQV. When the weight percentage of EQ 1 increased, the viability of HBMECs enhanced. An increase in the weight percentage of cholesterol, however, reduced the viability of HBMECs. The innovated CSLNs containing cholesterol can be effective in controlled release of SQV without inducing significant endothelial toxicity. PMID:22796778

  9. Effect of soluble copper released from copper oxide nanoparticles solubilisation on growth and photosynthetic processes of Lemna gibba L.

    PubMed

    Perreault, François; Samadani, Mahshid; Dewez, David

    2014-06-01

    Copper oxide nanoparticles (CuO NPs) are used as a biocide in paints, textiles and plastics. Their application may lead to the contamination of aquatic ecosystems, where potential environmental effects remain to be determined. Toxic effects may be related to interactions of NPs with cellular systems or to particles' solubilisation releasing metal ions. In this report, we evaluated CuO NPs and soluble copper effects on photosynthesis of the aquatic macrophyte Lemna gibba L to determine the role of particle solubility in NPs toxicity. When L. gibba plants were exposed 48 h to CuO NPs or soluble copper, inhibition of photosynthetic activity was found, indicated by the inactivation of Photosystem II reaction centers, a decrease in electron transport and an increase of thermal energy dissipation. Toxicity of CuO NPs was mainly driven by copper ions released from particles. However, the bioaccumulation of CuO NPs in plant was shown, indicating the need to evaluate organisms of higher trophic level. PMID:23521766

  10. TiO₂-based nanoparticles released in water from commercialized sunscreens in a life-cycle perspective: structures and quantities.

    PubMed

    Botta, Céline; Labille, Jérôme; Auffan, Mélanie; Borschneck, Daniel; Miche, Hélène; Cabié, Martiane; Masion, Armand; Rose, Jérôme; Bottero, Jean-Yves

    2011-06-01

    This work investigates the physical-chemical evolution during artificial aging in water of four commercialized sunscreens containing TiO₂-based nanocomposites. Sunscreens were analyzed in terms of mineralogy and TiO₂ concentration. The residues formed after aging were characterized in size, shape, chemistry and surface properties. The results showed that a significant fraction of nano-TiO₂ residues was released from all sunscreens, despite their heterogeneous behaviors. A stable dispersion of submicronic aggregates of nanoparticles was generated, representing up to 38 w/w% of the amount of sunscreen, and containing up to 30% of the total nano-TiO₂ initially present in the creams. The stability of the dispersion was tested as a function of salt concentration, revealing that in seawater conditions, a major part of these nano-TiO₂ residues will aggregate and sediment. These results were put in perspective with consumption and life cycle of sunscreens to estimate the amount of nano-TiO₂ potentially released into AQUATIC environment.

  11. A novel magnetic nanoparticle hyperthermia combined with ACMF-dependant drug release by DAMMs injection in VX-2 liver tumors.

    PubMed

    Zhang, Quanan; Tong, Jinlong; Chen, Huijuan; Jiang, Linlin; Zhu, Huiping; Zhu, Xiaofang; Yu, Hui; Liu, Jiwei; Liu, Baorui

    2012-01-01

    In this paper, we investigated the feasibility and effect of a novel combination therapy of magnetic nanoparticles (MNPs) hyperthermia with anticancer drugs for solid malignancies using doxorubicin-loaded alginate-templated magnetic microcapsules (DAMMs) in an animal liver cancer model. Firstly, DAMMs containing 18 nm gamma-Fe2O3 with doxorubicin (Dox) were synthesized and characterized. Then, the particular behavior of Dox release under external alternating current magnetic filed (ACMF) was tested in vitro. Moreover, to obtain accurate thermotherapy, the dose of DAMMs and temperature rise were computed by Hyperthermia treatment plan (HTP) and a fiber optic temperature sensor (FOTS) was used to monitor the temperature rise during treatments on VX-2 liver tumor-bearing rabbits. Furthermore, the therapeutic effect was studied by histopathological examinations and animal survival. The results showed that ACMF can induce Dox fast release during the treatment and the high MNPs content of DMMAs guaranteed the temperature rise for hyperthermia in tumors. The rabbits bearing VX-2 tumors in the magnetic hyperthermia using DMMAs group gained the most tumor necrosis and survival time. It was indicated that DAMMs-based magnetic hyperthermia could be a feasible and effective remedy which could be targeted at liver tumors by dual effects of hyperthermia and chemotherapy.

  12. Large intestine-targeted, nanoparticle-releasing oral vaccine to control genitorectal viral infection.

    PubMed

    Zhu, Qing; Talton, James; Zhang, Guofeng; Cunningham, Tshaka; Wang, Zijian; Waters, Robert C; Kirk, James; Eppler, Bärbel; Klinman, Dennis M; Sui, Yongjun; Gagnon, Susan; Belyakov, Igor M; Mumper, Russell J; Berzofsky, Jay A

    2012-08-01

    Both rectal and vaginal mucosal surfaces serve as transmission routes for pathogenic microorganisms. Vaccination through large intestinal mucosa, previously proven protective for both of these mucosal sites in animal studies, can be achieved successfully by direct intracolorectal (i.c.r.) administration, but this route is clinically impractical. Oral vaccine delivery seems preferable but runs the risk of the vaccine's destruction in the upper gastrointestinal tract. Therefore, we designed a large intestine-targeted oral delivery with pH-dependent microparticles containing vaccine nanoparticles, which induced colorectal immunity in mice comparably to colorectal vaccination and protected against rectal and vaginal viral challenge. Conversely, vaccine targeted to the small intestine induced only small intestinal immunity and provided no rectal or vaginal protection, demonstrating functional compartmentalization within the gut mucosal immune system. Therefore, using this oral vaccine delivery system to target the large intestine, but not the small intestine, may represent a feasible new strategy for immune protection of rectal and vaginal mucosa.

  13. Preparation of liposomal nanoparticles incorporating terbinafine in vitro drug release studies.

    PubMed

    Koutsoulas, Charalampos; Pippa, Natassa; Demetzos, Costas; Zabka, Marian

    2014-06-01

    Terbinafine hydrochloride (TBH) (E)-N-(6,6-dimethyl-2-hepten-4-inyl)-N-methyl-1-naphthaline-methanamine(-hydrochloride) is an effective antifungal agent already existing on the market in the form of topical formulations. The present study deals with the preparation and physicochemical characterization (size, polydispersity, zeta-potential) of 1,2-Diacyl-sn-glycero-3-phosphocholine (EggPC) incorporating TBH in two different dispersion media (tris-buffered saline (TBS) of pH 7.4 or in phosphate buffer solution (PS) of pH 5.5) in order to investigate how pH of dispersion media affects the incorporation efficiency of TBH into liposomes. There were further prepared three Carbopol 934 hydrogels of different concentrations (0.5, 1 and 2%) and their viscosity was measured and evaluated. Moreover, the in vitro drug release from three liposomal gels was studied, in order to investigate the ability of liposomes to act as carriers for TBH in a gel. All formulations were found to retain their original physicochemical properties at least for three weeks. These early studies on the release kinetics from liposomal gel show that Korsmeyer-Peppas model could be the best fitted model concerning the TBH release profile and could be supported biophysically from extended Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. PMID:24738424

  14. Fabrication and in vitro release behavior of a novel antibacterial coating containing halogenated furanone-loaded poly(L-lactic acid) nanoparticles on microarc-oxidized titanium

    PubMed Central

    Cheng, Yicheng; Wu, Jiang; Gao, Bo; Zhao, Xianghui; Yao, Junyan; Mei, Shenglin; Zhang, Liang; Ren, Huifang

    2012-01-01

    Background Dental implants have become increasingly common for the management of missing teeth. However, peri-implant infection remains a problem, is usually difficult to treat, and may lead eventually to dental implant failure. The aim of this study was to fabricate a novel antibacterial coating containing a halogenated furanone compound, ie, (Z-)-4-bromo-5-(bromomethylene)-2(5H)-furanone (BBF)-loaded poly(L-lactic acid) (PLLA) nanoparticles on microarc-oxidized titanium and to evaluate its release behavior in vitro. Methods BBF-loaded PLLA nanoparticles were prepared using the emulsion solvent-evaporation method, and the antibacterial coating was fabricated by cross-linking BBF-loaded PLLA nanoparticles with gelatin on microarc-oxidized titanium. Results The BBF-loaded PLLA nanoparticles had a small particle size (408 ± 14 nm), a low polydispersity index (0.140 ± 0.008), a high encapsulation efficiency (72.44% ± 1.27%), and a fine spherical shape with a smooth surface. The morphology of the fabricated antibacterial coating showed that the BBF-loaded PLLA nanoparticles were well distributed in the pores of the microarc oxidation coating, and were cross-linked with each other and the wall pores by gelatin. The release study indicated that the antibacterial coating could achieve sustained release of BBF for 60 days, with a slight initial burst release during the first 4 hours. Conclusion The novel antibacterial coating fabricated in this study is a potentially promising method for prevention of early peri-implant infection. PMID:23152682

  15. Silver speciation and characterization of nanoparticles released from plastic food containers by single particle ICPMS.

    PubMed

    Ramos, K; Gómez-Gómez, M M; Cámara, C; Ramos, L

    2016-05-01

    Silver migration from a commercial baby feeding bottle and a food box containing AgNPs, as confirmed by SEM-EDX analysis, was evaluated using food simulant solutions [i.e., water, 3% (v/v) acetic acid, and 10% and 90% (v/v) ethanol]. Silver release was investigated at temperatures in the 20-70°C range using contact times of up to 10 days. Migration of silver from the food box was in all cases 2 to 3 orders of magnitude higher than that observed for the baby bottle, although the total silver content in the original box material was half of that found in the baby bottle. As expected, for both food containers, silver migration depended on both the nature of the tested solution and the applied conditions. The highest release was observed for 3% acetic acid at 70°C for 2h, corresponding to 62ngdm(2) and 1887ngdm(-2) of silver for the baby bottle and the food box, respectively. Single particle-inductively coupled plasma mass spectrometry (SP-ICPMS) was used to characterise and quantify AgNPs in the food simulants extracts. Sample preparation was optimized to preserve AgNPs integrity. The experimental parameters affecting AgNPs detection, sizing and quantification by SP-ICPMS were also optimised. Analyses of water and acidic extracts revealed the presence of both dissolved silver and AgNPs. Small AgNPs (in the 18-30nm range) and particle number concentrations within the 4-1510 10(6)L(-1) range were detected, corresponding to only 0.1-8.6% of the total silver released from these materials. The only exception was AgNPs migrated into water at 40°C and 70°C from the food box, which accounted for as much as 34% and 69% of the total silver content, respectively.

  16. Silk fibroin nanoparticles constitute a vector for controlled release of resveratrol in an experimental model of inflammatory bowel disease in rats

    PubMed Central

    Lozano-Pérez, Antonio Abel; Rodriguez-Nogales, Alba; Ortiz-Cullera, Víctor; Algieri, Francesca; Garrido-Mesa, José; Zorrilla, Pedro; Rodriguez-Cabezas, M Elena; Garrido-Mesa, Natividad; Utrilla, M Pilar; De Matteis, Laura; de la Fuente, Jesús Martínez; Cenis, José Luis; Gálvez, Julio

    2014-01-01

    Purpose We aimed to evaluate the intestinal anti-inflammatory properties of silk fibroin nanoparticles, around 100 nm in size, when loaded with the stilbene compound resveratrol, in an experimental model of rat colitis. Methods Nanoparticles were loaded with resveratrol by adsorption. The biological effects of the resveratrol-loaded nanoparticles were tested both in vitro, in a cell culture of RAW 264.7 cells (mouse macrophages), and in vivo, in the trinitrobenzenesulfonic acid model of rat colitis, when administered intracolonically. Results The resveratrol liberation in 1× phosphate-buffered saline (PBS; pH 7.4) was characterized by fast liberation, reaching the solubility limit in 3 hours, which was maintained over a period of 80 hours. The in vitro assays revealed immunomodulatory properties exerted by these resveratrol-loaded nanoparticles since they promoted macrophage activity in basal conditions and inhibited this activity when stimulated with lipopolysaccharide. The in vivo experiments showed that after evaluation of the macroscopic symptoms, inflammatory markers, and intestinal barrier function, the fibroin nanoparticles loaded with resveratrol had a better effect than the single treatments, being similar to that produced by the glucocorticoid dexamethasone. Conclusion Silk fibroin nanoparticles constitute an attractive strategy for the controlled release of resveratrol, showing immunomodulatory properties and intestinal anti-inflammatory effects. PMID:25285004

  17. Comparative modeling of exposure to airborne nanoparticles released by consumer spray products.

    PubMed

    Riebeling, Christian; Luch, Andreas; Götz, Mario Enrico

    2016-01-01

    Consumer exposure to sprays containing nano-objects is a continuing concern as a potential health hazard. One potential hazard has been formulated in the overload hypothesis. It describes a volume fraction of the macrophages that is occupied by deposited nanoparticles that leads to reduced macrophage mobility. Subsequent chronic inflammation may then lead to severe health consequences including cancer. To calculate lung deposition of spherical particles, the Multiple-Path Particle Dosimetry (MPPD) model (ARA, Albuquerque, NM) provides different kinds of lung models and age settings. Using the MPPD v 2.11 software, we modeled several consumer-related exposure scenarios. Different body orientations and age groups were investigated. Moreover, a number of materials representing different densities were used, and the exposure calculated using MPPD is compared to the hazard derived from the overload hypothesis. Conditions leading to macrophage overload were found for exposures to high particle doses for prolonged times and repeated exposure. Such conditions are unlikely in the context of regular consumer exposure. The overload hypothesis assumes the particles to be inert and biopersistent, a condition that currently lacks a clear regulatory definition and is valid only for a few selected materials. Furthermore, because of material-specific effects and the possibility of surface adsorption of hazardous chemicals, nano-objects in propellant sprays remain of concern for consumer health.

  18. Comparison of dust released from sanding conventional and nanoparticle-doped wall and wood coatings

    PubMed Central

    Koponen, Ismo Kalevi; Jensen, Keld Alstrup; Schneider, Thomas

    2011-01-01

    Introduction of engineered nanoparticles (ENPs) into traditional surface coatings (e.g., paints, lacquers, fillers) may result in new exposures to both workers and consumers and possibly also a new risk to their health. During finishing and renovation, such products may also be a substantial source of exposure to ENPs or aggregates thereof. This study investigates the particle size distributions (5.6 nm–19.8 μm) and the total number of dust particles generated during sanding of ENP-doped paints, lacquers, and fillers as compared to their conventional counterparts. In all products, the dust emissions from sanding were found to consist of five size modes: three modes under 1 μm and two modes around 1 and 2 μm. Corrected for the emission from the sanding machine, the sanding dust, was dominated by 100–300 nm size particles, whereas the mass and surface area spectra were dominated by the micrometer modes. Adding ENPs to the studied products only vaguely affected the geometric mean diameters of the particle modes in the sanding dust when compared to their reference products. However, we observed considerable differences in the number concentrations in the different size modes, but still without revealing a clear effect of ENPs on dust emissions from sanding. PMID:20485339

  19. Comparison of non-crystalline silica nanoparticles in IL-1β release from macrophages

    PubMed Central

    2012-01-01

    Background Respirable crystalline silica (silicon dioxide; SiO2, quartz) particles are known to induce chronic inflammation and lung disease upon long-term inhalation, whereas non-crystalline (amorphous) SiO2 particles in the submicrometre range are regarded as less harmful. Several reports have demonstrated that crystalline, but also non-crystalline silica particles induce IL-1β release from macrophages via the NALP3-inflammasome complex (caspase-1, ASC and NALP3) in the presence of lipopolysaccharide (LPS) from bacteria. Our aim was to study the potential of different non-crystalline SiO2 particles from the nano- to submicro-sized range to activate IL-1β responses in LPS-primed RAW264.7 macrophages and primary rat lung macrophages. The role of the NALP3-inflammasome and up-stream mechanisms was further explored in RAW264.7 cells. Results In the present study, we have shown that 6 h exposure to non-crystalline SiO2 particles in nano- (SiNPs, 5–20 nm, 50 nm) and submicro-sizes induced strong IL-1β responses in LPS-primed mouse macrophages (RAW264.7) and primary rat lung macrophages. The primary lung macrophages were more sensitive to Si-exposure than the RAW-macrophages, and responded more strongly. In the lung macrophages, crystalline silica (MinUsil 5) induced IL-1β release more potently than the non-crystalline Si50 and Si500, when adjusted to surface area. This difference was much less pronounced versus fumed SiNPs. The caspase-1 inhibitor zYVAD and RNA silencing of the NALP3 receptor reduced the particle-induced IL-1β release in the RAW264.7 macrophages. Furthermore, inhibitors of phagocytosis, endosomal acidification, and cathepsin B activity reduced the IL-1β responses to the different particles to a similar extent. Conclusions In conclusion, non-crystalline silica particles in the nano- and submicro-size ranges seemed to induce IL-1β release from LPS-primed RAW264.7 macrophages via similar mechanisms as crystalline silica, involving particle

  20. Polymersome magneto-valves for reversible capture and release of nanoparticles

    PubMed Central

    van Rhee, P.G.; Rikken, R.S.M.; Abdelmohsen, L.K.E.A.; Maan, J.C.; Nolte, R.J.M.; van Hest, J.C.M.; Christianen, P.C.M.; Wilson, D.A.

    2014-01-01

    Stomatocytes are polymersomes with an infolded bowl-shaped architecture. This internal cavity is connected to the outside environment via a small ‘mouth’ region. Stomatocytes are assembled from diamagnetic amphiphilic block-copolymers with a highly anisotropic magnetic susceptibility, which permits to magnetically align and deform the polymeric self-assemblies. Here we show the reversible opening and closing of the mouth region of stomatocytes in homogeneous magnetic fields. The control over the size of the opening yields magneto-responsive supramolecular valves that are able to reversibly capture and release cargo. Furthermore, the increase in the size of the opening is gradual and starts at fields below 10 T, which opens the possibility of using these structures for delivery and nanoreactor applications. PMID:25248402

  1. Polymersome magneto-valves for reversible capture and release of nanoparticles

    NASA Astrophysics Data System (ADS)

    van Rhee, P. G.; Rikken, R. S. M.; Abdelmohsen, L. K. E. A.; Maan, J. C.; Nolte, R. J. M.; van Hest, J. C. M.; Christianen, P. C. M.; Wilson, D. A.

    2014-09-01

    Stomatocytes are polymersomes with an infolded bowl-shaped architecture. This internal cavity is connected to the outside environment via a small ‘mouth’ region. Stomatocytes are assembled from diamagnetic amphiphilic block-copolymers with a highly anisotropic magnetic susceptibility, which permits to magnetically align and deform the polymeric self-assemblies. Here we show the reversible opening and closing of the mouth region of stomatocytes in homogeneous magnetic fields. The control over the size of the opening yields magneto-responsive supramolecular valves that are able to reversibly capture and release cargo. Furthermore, the increase in the size of the opening is gradual and starts at fields below 10 T, which opens the possibility of using these structures for delivery and nanoreactor applications.

  2. Polymersome magneto-valves for reversible capture and release of nanoparticles.

    PubMed

    van Rhee, P G; Rikken, R S M; Abdelmohsen, L K E A; Maan, J C; Nolte, R J M; van Hest, J C M; Christianen, P C M; Wilson, D A

    2014-01-01

    Stomatocytes are polymersomes with an infolded bowl-shaped architecture. This internal cavity is connected to the outside environment via a small 'mouth' region. Stomatocytes are assembled from diamagnetic amphiphilic block-copolymers with a highly anisotropic magnetic susceptibility, which permits to magnetically align and deform the polymeric self-assemblies. Here we show the reversible opening and closing of the mouth region of stomatocytes in homogeneous magnetic fields. The control over the size of the opening yields magneto-responsive supramolecular valves that are able to reversibly capture and release cargo. Furthermore, the increase in the size of the opening is gradual and starts at fields below 10 T, which opens the possibility of using these structures for delivery and nanoreactor applications. PMID:25248402

  3. PLGA nanoparticles for oral delivery of hydrophobic drugs: influence of organic solvent on nanoparticle formation and release behavior in vitro and in vivo using estradiol as a model drug.

    PubMed

    Sahana, D K; Mittal, G; Bhardwaj, V; Kumar, M N V Ravi

    2008-04-01

    The aim of present investigation was to screen different solvents for optimizing nanoparticle preparation in terms of particle size, entrapment efficiency, and finally, release behavior using a model drug estradiol. Nanoparticles were prepared following emulsion-diffusion-evaporation method using didodecyldimethyl ammonium bromide (DMAB) or polyvinyl alcohol (PVA) as stabilizers. Ethyl acetate (EA), acetone (ACE), chloroform (CHL), and dichloromethane (DCM) were used as organic solvents either individually or in combinations. DMAB when used as surfactant led to smaller particle size as compared to PVA irrespective of the solvents and combinations used, but on the other hand, PVA produced particles with higher entrapment when combinations of solvents used. DCM in combination with EA resulted in highest entrapment with both the stabilizers. All the formulations exhibited similar in vitro release profile (Zero order) irrespective of stabilizer (DMAB or PVA) used, however, the average release per day was higher in case of DCM formulations due to greater entrapment. In situ uptake studies suggest that smaller the particle size better is the uptake. The bioavailability from nanoparticles was assessed in male Sprague Dawley (SD) rats at a dose of 1 mg drug/rat. EA/DMAB (size 116.0 +/- 2.6 nm) and DCM:EA 70:30/DMAB (size 253.0 +/- 5.5 nm) showed the release for 9 and 5 days, respectively, whereas EA/PVA (size 279.3 +/- 2.5 nm) released the drug over the periods of 3 days suggesting that particle size has significant role in determining the fate of nanoparticles in vivo. Histopathological examination revealed absence of any inflammatory response with the formulations under the studied period.

  4. 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

  5. Growth kinetics and mechanistic action of reactive oxygen species released by silver nanoparticles from Aspergillus niger on Escherichia coli.

    PubMed

    Ninganagouda, Shivaraj; Rathod, Vandana; Singh, Dattu; Hiremath, Jyoti; Singh, Ashish Kumar; Mathew, Jasmine; ul-Haq, Manzoor

    2014-01-01

    Silver Nanoparticles (AgNPs), the real silver bullet, are known to have good antibacterial properties against pathogenic microorganisms. In the present study AgNPs were prepared from extracellular filtrate of Aspergillus niger. Characterization of AgNPs by UV-Vis spectrum reveals specific surface plasmon resonance at peak 416 nm; TEM photographs revealed the size of the AgNPs to be 20-55 nm. Average diameter of the produced AgNPs was found to be 73 nm with a zeta potential that was -24 mV using Malvern Zetasizer. SEM micrographs showed AgNPs to be spherical with smooth morphology. EDS revealed the presence of pure metallic AgNPs along with carbon and oxygen signatures. Of the different concentrations (0, 2.5, 5, 10, and 15 μg/mL) used 10 μg/mL were sufficient to inhibit 10(7) CFU/mL of E. coli. ROS production was measured using DCFH-DA method and the the free radical generation effect of AgNPs on bacterial growth inhibition was investigated by ESR spectroscopy. This paper not only deals with the damage inflicted on microorganisms by AgNPs but also induces cell death through the production of ROS released by AgNPs and also growth kinetics of E. coli supplemented with AgNPs produced by A. niger. PMID:25028666

  6. Growth Kinetics and Mechanistic Action of Reactive Oxygen Species Released by Silver Nanoparticles from Aspergillus niger on Escherichia coli

    PubMed Central

    Ninganagouda, Shivaraj; Rathod, Vandana; Singh, Dattu; Hiremath, Jyoti; Singh, Ashish Kumar; Mathew, Jasmine; ul-Haq, Manzoor

    2014-01-01

    Silver Nanoparticles (AgNPs), the real silver bullet, are known to have good antibacterial properties against pathogenic microorganisms. In the present study AgNPs were prepared from extracellular filtrate of Aspergillus niger. Characterization of AgNPs by UV-Vis spectrum reveals specific surface plasmon resonance at peak 416 nm; TEM photographs revealed the size of the AgNPs to be 20–55 nm. Average diameter of the produced AgNPs was found to be 73 nm with a zeta potential that was −24 mV using Malvern Zetasizer. SEM micrographs showed AgNPs to be spherical with smooth morphology. EDS revealed the presence of pure metallic AgNPs along with carbon and oxygen signatures. Of the different concentrations (0, 2.5, 5, 10, and 15 μg/mL) used 10 μg/mL were sufficient to inhibit 107 CFU/mL of E. coli. ROS production was measured using DCFH-DA method and the the free radical generation effect of AgNPs on bacterial growth inhibition was investigated by ESR spectroscopy. This paper not only deals with the damage inflicted on microorganisms by AgNPs but also induces cell death through the production of ROS released by AgNPs and also growth kinetics of E. coli supplemented with AgNPs produced by A. niger. PMID:25028666

  7. Design and Synthesis of Core-Shell-Shell Upconversion Nanoparticles for NIR-Induced Drug Release, Photodynamic Therapy, and Cell Imaging.

    PubMed

    Wang, Hao; Han, Ren-lu; Yang, Li-ming; Shi, Jun-hui; Liu, Zong-jun; Hu, Yu; Wang, You; Liu, Shu-juan; Gan, Yang

    2016-02-01

    Novel core-shell-shell structured nanoparticles 75 nm in diameter with all-in-one "smart" functional capabilities for simultaneous photoresponsive drug release, photodynamic therapy, and cell imaging are designed and prepared. These nanoparticles consist of an upconversion (UC) emission core, a photosensitizer-embodied silica sandwich shell, and a β-cyclodextrin (β-CD) gated mesoporous silica outmost shell with drugs (Rhodamine B as a model) loaded inside. We show in this proof-of-concept demonstration that, under 980 nm near-infrared irradiation, UC 540 nm green light emissions were emitted for cell imaging, and 660 nm red light emissions were excited for activating photosensitizers to generate singlet oxygen, which could be exploited directly to kill cancer cells and simultaneously dissociate β-CD gatekeeper to release drugs. The preliminary results reported here will shed new light on the future design and applications of multifunctional platforms for cancer therapy and diagnostic. PMID:26816249

  8. Recent Advances in Nanoparticle-Based Förster Resonance Energy Transfer for Biosensing, Molecular Imaging and Drug Release Profiling

    PubMed Central

    Chen, Nai-Tzu; Cheng, Shih-Hsun; Liu, Ching-Ping; Souris, Jeffrey S.; Chen, Chen-Tu; Mou, Chung-Yuan; Lo, Leu-Wei

    2012-01-01

    Förster resonance energy transfer (FRET) may be regarded as a “smart” technology in the design of fluorescence probes for biological sensing and imaging. Recently, a variety of nanoparticles that include quantum dots, gold nanoparticles, polymer, mesoporous silica nanoparticles and upconversion nanoparticles have been employed to modulate FRET. Researchers have developed a number of “visible” and “activatable” FRET probes sensitive to specific changes in the biological environment that are especially attractive from the biomedical point of view. This article reviews recent progress in bringing these nanoparticle-modulated energy transfer schemes to fruition for applications in biosensing, molecular imaging and drug delivery. PMID:23443121

  9. Improved insulin loading in poly(lactic-co-glycolic) acid (PLGA) nanoparticles upon self-assembly with lipids.

    PubMed

    García-Díaz, María; Foged, Camilla; Nielsen, Hanne Mørck

    2015-03-30

    Polymeric nanoparticles are widely investigated as drug delivery systems for oral administration. However, the hydrophobic nature of many polymers hampers effective loading of the particles with hydrophilic macromolecules such as insulin. Thus, the aim of this work was to improve the loading of insulin into poly(lactic-co-glycolic) acid (PLGA) nanoparticles by pre-assembly with amphiphilic lipids. Insulin was complexed with soybean phosphatidylcholine or sodium caprate by self-assembly and subsequently loaded into PLGA nanoparticles by using the double emulsion-solvent evaporation technique. The nanoparticles were characterized in terms of size, zeta potential, insulin encapsulation efficiency and loading capacity. Upon pre-assembly with lipids, there was an increased distribution of insulin into the organic phase of the emulsion, eventually resulting in significantly enhanced encapsulation efficiencies (90% as compared to 24% in the absence of lipids). Importantly, the insulin loading capacity was increased up to 20% by using the lipid-insulin complexes. The results further showed that a main fraction of the lipid was incorporated into the nanoparticles and remained associated to the polymer during release studies in buffers, whereas insulin was released in a non-complexed form as a burst of approximately 80% of the loaded insulin. In conclusion, the protein load in PLGA nanoparticles can be significantly increased by employing self-assembled protein-lipid complexes.

  10. In vitro release characteristics and cellular uptake of poly(D,L-lactic-co-glycolic acid) nanoparticles for topical delivery of antisense oligodeoxynucleotides.

    PubMed

    Chen, Ying-Shan; Alany, Raid G; Young, Simon A; Green, Colin R; Rupenthal, Ilva D

    2011-01-01

    The efficacy of antisense oligodeoxynucleotides (AsODNs) is compromised by their poor stability in biological fluids and the inefficient cellular uptake due to their size and negative charge. Since chemical modifications of these molecules have resulted in a number of non-antisense activities, incorporation into particulate delivery systems has offered a promising alternative. The aim of this study was to evaluate various poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles for AsODN entrapment and delivery. PLGA nanoparticles were prepared using the double emulsion solvent evaporation method. The influence of formulation parameters such as PLGA concentration and volume ratio of internal aqueous phase volume (Va1) to organic phase volume (Vo) to external aqueous phase volume (Va2) on particle size, polydispersity index (PDI) and zeta potential (ZP) was investigated using a full factorial study. The particle size increased with increasing PLGA concentrations and volume ratios, with an interaction detectable between the two factors. AsODN entrapment efficiencies ranged between 49.97% and 54.95% with no significant difference between various formulations. By fitting the in vitro release profiles to a dual first order release model it was shown that the AsODN release occurred via two processes: a diffusion controlled process in the early phase (25 to 32% within one day) and a PLGA degradation process in the latter (39 to 70% after 14 days). Cellular uptake studies using primary corneal epithelial cells suggested active transport of nanoparticles via endocytosis. PLGA nanoparticles therefore show potential to successfully entrap AsODNs, transport them into cells and release them over time due to polymer erosion.

  11. Light-responsive nanoparticle depot to control release of a small molecule angiogenesis inhibitor in the posterior segment of the eye

    PubMed Central

    Anh Nguyen Huu, Viet; Luo, Jing; Zhu, Jie; Zhu, Jing; Patel, Sherrina; Boone, Alexander; Mahmoud, Enas; McFearin, Cathryn; Olejniczak, Jason; de Gracia Lux, Caroline; Lux, Jacques; Fomina, Nadezda; Huynh, Michelle; Zhang, Kang; Almutairi, Adah

    2015-01-01

    Therapies for macular degeneration and diabetic retinopathy require intravitreal injections every 4-8 weeks. Injections are uncomfortable, time-consuming, and carry risks of infection and retinal damage. However, drug delivery via noninvasive methods to the posterior segment of the eye has been a major challenge due to the eye's unique anatomy and physiology. Here we present a novel nanoparticle depot platform for on-demand drug delivery using a far ultraviolet (UV) light-degradable polymer, which allows noninvasively triggered drug release using brief, low-power light exposure. Nanoparticles stably retain encapsulated molecules in the vitreous, and can release cargo in response to UV exposure up to 30 weeks post-injection. Light-triggered release of nintedanib (BIBF 1120), a small molecule angiogenesis inhibitor, 10 weeks post-injection suppresses choroidal neovascularization (CNV) in rats. Light-sensitive nanoparticles are biocompatible and cause no adverse effects on the eye as assessed by electroretinograms (ERG), corneal and retinal tomography, and histology. PMID:25571784

  12. Multifunctional PEG modified DOX loaded mesoporous silica nanoparticle@CuS nanohybrids as photo-thermal agent and thermal-triggered drug release vehicle for hepatocellular carcinoma treatment

    NASA Astrophysics Data System (ADS)

    Wu, Lingjie; Wu, Ming; Zeng, Yongyi; Zhang, Da; Zheng, Aixian; Liu, Xiaolong; Liu, Jingfeng

    2015-01-01

    The combination of a multi-therapeutic mode with a controlled fashion is a key improvement in nanomedicine. Here, we synthesized polyethylene glycol (PEG)-modified doxorubicin (DOX)-loaded mesoporous silica nanoparticle (MSN) @CuS nanohybrids as efficient drug delivery carriers, combined with photothermal therapy and chemotherapy to enhance the therapeutic efficacy on hepatocellular carcinoma (HCC). The physical properties of the nanohybrids were characterized by transmission electron microscopy (TEM), N2 adsorption and desorption experiments and by the Vis-NIR absorption spectra. The results showed that the doxorubicin could be stored in the inner pores of mesoporous silica nanoparticles; the CuS nanoparticles, which are coated on the surface of a mesoporous silica nanoparticle, could serve as efficient photothermal therapy (PTT) agents; the loaded drug release could be easily triggered by NIR irradiation. The combination of the PTT treatment with controlled chemotherapy could further enhance the cancer ablation ability compared to any of the single approaches alone. Hence, the reported PEG-modified DOX-loaded mesoporous silica nanoparticle@CuS nanohybrids might be very promising therapeutic agents for HCC treatment.

  13. Iron oxide nanoparticles show no toxicity in the comet assay in lymphocytes: A promising vehicle as a nitric oxide releasing nanocarrier in biomedical applications

    NASA Astrophysics Data System (ADS)

    de Lima, R.; Oliveira, J. L.; Murakami, P. S. K.; Molina, M. A. M.; Itri, R.; Haddad, P.; Seabra, A. B.

    2013-04-01

    This work reports the synthesis and toxicological evaluation of surface modified magnetic iron oxide nanoparticles as vehicles to carry and deliver nitric oxide (NO). The surface of the magnetic nanoparticles (MNPs) was coated with two thiol-containing hydrophilic ligands: mercaptosuccinic acid (MSA) or dimercaptosuccinic acid (DMSA), leading to thiolated MNPs. Free thiols groups on the surface of MSA- or DMSA-MNPs were nitrosated leading to NO-releasing MNPs. The genotoxicity of thiolated-coated MNPs was evaluated towards human lymphocyte cells by the comet assay. No genotoxicity was observed due to exposure of human lymphocytes to MSA- or DMSA-MNPs, indicating that these nanovectors can be used as inert vehicles in drug delivery, in biomedical applications. On the other hand, NO-releasing MPNs showed genotoxicity and apoptotic activities towards human lymphocyte cell cultures. These results indicate that NO-releasing MNPs may result in important biomedical applications, such as the treatment of tumors, in which MNPs can be guided to the target site through the application of an external magnetic field, and release NO directly to the desired site of action.

  14. Radio-frequency triggered heating and drug release using doxorubicin-loaded LSMO nanoparticles for bimodal treatment of breast cancer.

    PubMed

    Kulkarni, Vaishnavi M; Bodas, Dhananjay; Dhoble, Deepa; Ghormade, Vandana; Paknikar, Kishore

    2016-09-01

    Radio-frequency responsive nanomaterials combined with drugs for simultaneous hyperthermia and drug delivery are potential anti-cancer agents. In this study, chitosan coated La0.7Sr0.3MnO3 nanoparticles (C-LSMO NPs) were synthesized and characterized by X-ray diffraction, dynamic light scattering, Fourier transform infra red spectroscopy, vibrating sample magnetometer, scanning electron and atomic force microscopy. Under low radio-frequency (365kHz, RF), C-LSMO NPs (90nm) showed good colloidal stability (+22mV), superparamagnetic nature (15.4 emu/g) and heating capacity (57.4W/g SAR value). Chitosan facilitated doxorubicin entrapment (76%) resulted in DC-LSMO NPs that showed drug release upon a 5min RF exposure. MCF-7 and MDA-MB-231 cancer cells responded to a 5min RF exposure in the presence of bimodal DC-LSMO NPs with a significant decrease in viability to 73% and 88% (Pearson correlation, r=1, P<0.01) respectively, as compared to hyperthermia alone. Internalization of DC-LSMO NPs via the endosomal pathway led to an efficient localization of doxorubicin within the cell nucleus. The ensuing DNA damage, heat shock protein induction, and caspase production triggered apoptotic cell death. Moreover, DC-LSMO NPs successfully restricted the migration of metastatic MDA-MB-231 cancer cells. These data suggest that DC-LSMO NPs are potential bimodal therapeutic agents for cancer treatment and hold promise against disease recurrence and drug resistance. PMID:27337564

  15. nanoparticles

    NASA Astrophysics Data System (ADS)

    Andreu-Cabedo, Patricia; Mondragon, Rosa; Hernandez, Leonor; Martinez-Cuenca, Raul; Cabedo, Luis; Julia, J. Enrique

    2014-10-01

    Thermal energy storage (TES) is extremely important in concentrated solar power (CSP) plants since it represents the main difference and advantage of CSP plants with respect to other renewable energy sources such as wind, photovoltaic, etc. CSP represents a low-carbon emission renewable source of energy, and TES allows CSP plants to have energy availability and dispatchability using available industrial technologies. Molten salts are used in CSP plants as a TES material because of their high operational temperature and stability of up to 500°C. Their main drawbacks are their relative poor thermal properties and energy storage density. A simple cost-effective way to improve thermal properties of fluids is to dope them with nanoparticles, thus obtaining the so-called salt-based nanofluids. In this work, solar salt used in CSP plants (60% NaNO3 + 40% KNO3) was doped with silica nanoparticles at different solid mass concentrations (from 0.5% to 2%). Specific heat was measured by means of differential scanning calorimetry (DSC). A maximum increase of 25.03% was found at an optimal concentration of 1 wt.% of nanoparticles. The size distribution of nanoparticle clusters present in the salt at each concentration was evaluated by means of scanning electron microscopy (SEM) and image processing, as well as by means of dynamic light scattering (DLS). The cluster size and the specific surface available depended on the solid content, and a relationship between the specific heat increment and the available particle surface area was obtained. It was proved that the mechanism involved in the specific heat increment is based on a surface phenomenon. Stability of samples was tested for several thermal cycles and thermogravimetric analysis at high temperature was carried out, the samples being stable.

  16. Drug release and skin penetration from solid lipid nanoparticles and a base cream: a systematic approach from a comparison of three glucocorticoids.

    PubMed

    Schlupp, P; Blaschke, T; Kramer, K D; Höltje, H-D; Mehnert, W; Schäfer-Korting, M

    2011-01-01

    Solid lipid nanoparticles (SLNs) can enhance drug penetration into the skin, yet the mechanism of the improved transport is not known in full. To unravel the influence of the drug-particle interaction on penetration enhancement, 3 glucocorticoids (GCs), prednisolone (PD), the diester prednicarbate (PC) and the monoester betamethasone 17-valerate (BMV), varying in structure and lipophilicity, were loaded onto SLNs. Theoretical permeability coefficients (cm/s) of the agents rank BMV (-6.38) ≥ PC (-6.57) > PD (-7.30). GC-particle interaction, drug release and skin penetration were investigated including a conventional oil-in-water cream for reference. Both with SLN and cream, PD release was clearly superior to PC release which exceeded BMV release. With the cream, the rank order did not change when studying skin penetration, and skin penetration is thus predominantly influenced by drug release. Yet, the penetration profile for the GCs loaded onto SLNs completely changed, and differences between the steroids were almost lost. Thus, SLNs influence skin penetration by an intrinsic mechanism linked to a specific interaction of the drug-carrier complex and the skin surface, which becomes possible by the lipid nature and nanosize of the carrier and appears not to be derived by testing drug release. Interestingly, PC and PD uptake from SLN even resulted in epidermal targeting. Thus, SLNs are not only able to improve skin penetration of topically applied drugs, but may also be of particular interest when specifically aiming to influence epidermal dysfunction.

  17. In-vitro release and permeation studies of ketoconazole from optimized dermatological vehicles using powder, nanoparticles and solid dispersion forms of drug

    NASA Astrophysics Data System (ADS)

    Mohammed, Irfan A.

    To optimize the clinical efficacy of Ketoconazole from an externally applied product, this project was undertaken to evaluate the drug release/permeation profile from various dermatological vehicles using regular powder, nanoparticles and solid dispersion forms with reduced level of drug. Nanoparticles of drug were prepared by wet media milling method using Polyvinylpyrrolidone (PVP-10K) as a stabilizer. The nanoparticles were in the size range of 250-300nm. Solid dispersion was prepared by solvent evaporation method using drug to PVP-10K at a weight ratio of (1:2). Formulations containing 1% w/w drug were developed using HPMC gel, Carbomer gel and a cationic cream as the vehicles. Penetration enhancers including propylene glycol (PG), dimethylsulfoxide (DMSO) and polyethylene glycol 400 (PEG-400) at various levels were evaluated. A commercial 2% w/w ketoconazole product was included as a control for comparison. Studies were carried out with Franz Diffusion Cells using cellulose membrane and human cadaver skin for two and six hour studies. Among the formulations evaluated, the general rank order of the drug release through the cellulose membrane was observed to be: HPMC gel base > Anionic gel base > Cationic gel base > Commercial product. The addition of penetration enhancers showed variable effects in all samples evaluated. However, the HPMC gel-based vehicle showed significant effect in enhancing the drug release in the presence of DMSO. The formulation containing 1% w/w ketoconazole and 20% w/w DMSO gave a maximum drug release of 20.21% when compared to only 1.60% from the commercial product. This represents a twelve fold increase in the release of ketoconazole from the formulation. Furthermore, when the optimum gel-based formulation containing 1% w/w ketoconazole was studied over an extended period of 6 hours, it gave 36.01% drug release from the sample formulation compared to only 2.00% from the commercial product. Finally, this formulation was selected to

  18. Induction of apoptosis in cancer cells by NiZn ferrite nanoparticles through mitochondrial cytochrome C release

    PubMed Central

    Al-Qubaisi, Mothanna Sadiq; Rasedee, Abdullah; Flaifel, Moayad Husein; Ahmad, Sahrim Hj; Hussein-Al-Ali, Samer; Hussein, Mohd Zobir; Zainal, Zulkarnain; Alhassan, Fatah H; Taufiq-Yap, Yun H; Eid, Eltayeb EM; Arbab, Ismail Adam; Al-Asbahi, Bandar A; Webster, Thomas J; Zowalaty, Mohamed Ezzat El

    2013-01-01

    The long-term objective of the present study was to determine the ability of NiZn ferrite nanoparticles to kill cancer cells. NiZn ferrite nanoparticle suspensions were found to have an average hydrodynamic diameter, polydispersity index, and zeta potential of 254.2 ± 29.8 nm, 0.524 ± 0.013, and −60 ± 14 mV, respectively. We showed that NiZn ferrite nanoparticles had selective toxicity towards MCF-7, HepG2, and HT29 cells, with a lesser effect on normal MCF 10A cells. The quantity of Bcl-2, Bax, p53, and cytochrome C in the cell lines mentioned above was determined by colorimetric methods in order to clarify the mechanism of action of NiZn ferrite nanoparticles in the killing of cancer cells. Our results indicate that NiZn ferrite nanoparticles promote apoptosis in cancer cells via caspase-3 and caspase-9, downregulation of Bcl-2, and upregulation of Bax and p53, with cytochrome C translocation. There was a concomitant collapse of the mitochondrial membrane potential in these cancer cells when treated with NiZn ferrite nanoparticles. This study shows that NiZn ferrite nanoparticles induce glutathione depletion in cancer cells, which results in increased production of reactive oxygen species and eventually, death of cancer cells. PMID:24204141

  19. Magneto-controllable capture and release of cancer cells by using a micropillar device decorated with graphite oxide-coated magnetic nanoparticles.

    PubMed

    Yu, Xiaolei; He, Rongxiang; Li, Shasha; Cai, Bo; Zhao, Libo; Liao, Lei; Liu, Wei; Zeng, Qian; Wang, Hao; Guo, Shi-Shang; Zhao, Xing-Zhong

    2013-11-25

    Aiming to highly efficient capture and analysis of circulating tumor cells, a micropillar device decorated with graphite oxide-coated magnetic nanoparticles is developed for magneto-controllable capture and release of cancer cells. Graphite oxide-coated, Fe3 O4 magnetic nanoparticles (MNPs) are synthesized by solution mixing and functionalized with a specific antibody, following by the immobilization of such modified MNPs on our designed micropillar device. For the proof-of-concept study, a HCT116 colorectal cancer cell line is employed to exam the capture efficiency. Under magnetic field manipulation, the high density packing of antibody-modified MNPs on the micropillars increases the local concentration of antibody, as well as the topographic interactions between cancer cells and micropillar surfaces. The flow rate and the micropillar geometry are optimized by studying their effects on capture efficiency. Then, a different number of HCT116 cells spiked in two kinds of cell suspension are investigated, yielding capture efficiency >70% in culture medium and >40% in blood sample, respectively. Moreover, the captured HCT116 cells are able to be released from the micropillars with a saturated efficiency of 92.9% upon the removal of applied magnetic field and it is found that 78% of the released cancer cells are viable, making them suitable for subsequent biological analysis.

  20. Nanoparticles of lipid monolayer shell and biodegradable polymer core for controlled release of paclitaxel: effects of surfactants on particles size, characteristics and in vitro performance.

    PubMed

    Liu, Yutao; Pan, Jie; Feng, Si-Shen

    2010-08-16

    This work developed a system of nanoparticles of lipid monolayer shell and biodegradable polymer core for controlled release of anticancer drugs with paclitaxel as a model drug, in which the emphasis was given to the effects of the surfactant type and the optimization of the emulsifier amount used in the single emulsion solvent evaporation/extraction process for the nanoparticle preparation on the particle size, characters and in vitro performance. The drug loaded nanoparticles were characterized by laser light scattering (LLS) for size and size distribution, field-emission scanning electron microscopy (FESEM) for surface morphology, X-ray photoelectron spectroscopy (XPS) for surface chemistry, zetasizer for surface charge, and high performance liquid chromatography (HPLC) for drug encapsulation efficiency and in vitro drug release kinetics. MCF-7 breast cancer cells were employed to evaluate the cellular uptake and cytotoxicity. It was found that phospholipids of short chains such as 1,2-dilauroylphosphatidylocholine (DLPC) have great advantages over the traditional emulsifier poly(vinyl alcohol) (PVA), which is used most often in the literature, in preparation of nanoparticles of biodegradable polymers such as poly(D,L-lactide-co-glycolide) (PLGA) for desired particle size, character and in vitro cellular uptake and cytotoxicity. After incubation with MCF-7 cells at 0.250 mg/ml NP concentration, the coumarin-6 loaded PLGA NPs of DLPC shell showed more effective cellular uptake versus those of PVA shell. The analysis of IC(50), i.e. the drug concentration at which 50% of the cells are killed, demonstrated that our DLPC shell PLGA core NP formulation of paclitaxel could be 5.88-, 5.72-, 7.27-fold effective than the commercial formulation Taxol after 24, 48, 72h treatment, respectively. PMID:20472049

  1. Doxorubicin-Incorporated Nanotherapeutic Delivery System Based on Gelatin-Coated Gold Nanoparticles: Formulation, Drug Release, and Multimodal Imaging of Cellular Internalization.

    PubMed

    Suarasan, Sorina; Focsan, Monica; Potara, Monica; Soritau, Olga; Florea, Adrian; Maniu, Dana; Astilean, Simion

    2016-09-01

    In this work, we developed a new pH- and temperature-responsive nanochemotherapeutic system based on Doxorubicin (DOX) noncovalently bound to biosynthesized gelatin-coated gold nanoparticles (DOX-AuNPs@gelatin). The real-time release profile of DOX was evaluated at different pH values (7.4, 5.3, and 4.6) and temperatures (22-45 °C) in aqueous solutions, and its therapeutic performance was examined in vitro against MCF-7 breast cancer cells. TEM, dark-field scattering, and wide-field fluorescence microscopy indicated the effective uptake of nanochemotherapeutics with the subsequent release and progressive accumulation of DOX in cell nuclei. MTT assays clearly showed the effectiveness of the treatment by inhibiting the growth of MCF-7 breast cancer cells for a loaded drug concentration of 5 μg/mL. The most informative data about the dynamic release and localization were provided by scanning confocal microscopy using time-resolved fluorescence and surface-enhanced Raman scattering (SERS) techniques. In particular, fluorescence-lifetime imaging (FLIM) recorded under 485 nm pulsed diode laser excitation revealed the bimodal distribution of DOX in cells. The shorter fluorescence lifetime of DOX localized in nuclei (1.52 ns) than in the cytoplasm (2.4 ns) is consistent with the cytotoxic mechanism induced by DOX-DNA intercalation. Remarkably, the few DOX molecules captured between nanoparticles ("electromagnetic hotspots") after most drug is released act as SERS reporters for the localization of plasmonic nanocarriers in MCF-7 cells. The high drug loading capacity and effective drug release under pH control combined with the advantage of multimodal visualization inside cells clearly indicate the high potential of our DOX-AuNPs@gelatin delivery system for implementation in nanomedicine.

  2. Polymeric nanoparticles loaded with the 3,5,3′-triiodothyroacetic acid (Triac), a thyroid hormone: factorial design, characterization, and release kinetics

    PubMed Central

    dos Santos, Karen C; da Silva, Maria Fatima GF; Pereira-Filho, Edenir R; Fernandes, Joao B; Polikarpov, Igor; Forim, Moacir R

    2012-01-01

    This present investigation deals with the development and optimization of polymeric nanoparticle systems loaded with 3,5,3′-triiodothyroacetic acid (Triac). A 211–6 fractional factorial design and another 22 factorial design were used to study the contrasts on particle size distribution, morphology, surface charge, drug content, entrapment efficiency, and in vitro drug release profiles. The independent variables were the concentration of Triac, type and quantity of both polymer and oil, quantity of Span™ 60 and Tween® 80, volume of solvent and water, and velocity of both magnetic stirring and the transfer of the organic phase into the aqueous solution. The results of optimized formulations showed a narrow size distribution with a polydispersity index lower than 0.200. The particle sizes were on average 159.6 nm and 285.6 nm for nanospheres and nanocapsules, respectively. The zeta potential was higher than 20 mV (in module) and the entrapment efficiency was nearly 100%. A high-performance liquid chromatography method was developed, validated, and efficiently applied to Triac quantification in colloidal suspension. The main independent variables were the type and quantity of the polymer and oil. In vitro drug release profile depicted several features to sustain Triac release. Different formulations showed various release rates indicating an interaction between Triac and other formulation compounds such as polymer and/or oil quantity. Two different models were identified (biexponential and monoexponential) that allowed the control of both the release rate and Triac concentration. Thus, the prepared nanoparticles described here may be of clinical importance in delivering Triac for thyroid treatment. PMID:24198495

  3. Doxorubicin-Incorporated Nanotherapeutic Delivery System Based on Gelatin-Coated Gold Nanoparticles: Formulation, Drug Release, and Multimodal Imaging of Cellular Internalization.

    PubMed

    Suarasan, Sorina; Focsan, Monica; Potara, Monica; Soritau, Olga; Florea, Adrian; Maniu, Dana; Astilean, Simion

    2016-09-01

    In this work, we developed a new pH- and temperature-responsive nanochemotherapeutic system based on Doxorubicin (DOX) noncovalently bound to biosynthesized gelatin-coated gold nanoparticles (DOX-AuNPs@gelatin). The real-time release profile of DOX was evaluated at different pH values (7.4, 5.3, and 4.6) and temperatures (22-45 °C) in aqueous solutions, and its therapeutic performance was examined in vitro against MCF-7 breast cancer cells. TEM, dark-field scattering, and wide-field fluorescence microscopy indicated the effective uptake of nanochemotherapeutics with the subsequent release and progressive accumulation of DOX in cell nuclei. MTT assays clearly showed the effectiveness of the treatment by inhibiting the growth of MCF-7 breast cancer cells for a loaded drug concentration of 5 μg/mL. The most informative data about the dynamic release and localization were provided by scanning confocal microscopy using time-resolved fluorescence and surface-enhanced Raman scattering (SERS) techniques. In particular, fluorescence-lifetime imaging (FLIM) recorded under 485 nm pulsed diode laser excitation revealed the bimodal distribution of DOX in cells. The shorter fluorescence lifetime of DOX localized in nuclei (1.52 ns) than in the cytoplasm (2.4 ns) is consistent with the cytotoxic mechanism induced by DOX-DNA intercalation. Remarkably, the few DOX molecules captured between nanoparticles ("electromagnetic hotspots") after most drug is released act as SERS reporters for the localization of plasmonic nanocarriers in MCF-7 cells. The high drug loading capacity and effective drug release under pH control combined with the advantage of multimodal visualization inside cells clearly indicate the high potential of our DOX-AuNPs@gelatin delivery system for implementation in nanomedicine. PMID:27537061

  4. A study of chitosan hydrogel with embedded mesoporous silica nanoparticles loaded by ibuprofen as a dual stimuli-responsive drug release system for surface coating of titanium implants.

    PubMed

    Zhao, Pengkun; Liu, Hongyu; Deng, Hongbing; Xiao, Ling; Qin, Caiqin; Du, Yumin; Shi, Xiaowen

    2014-11-01

    In this study, the complex pH and electro responsive system made of chitosan hydrogel with embedded mesoporous silica nanoparticles (MSNs) was evaluated as a tunable drug release system. As a model drug, ibuprofen (IB) was used; its adsorption in MSNs was evidenced by Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and thermogravimetric analysis (TG). In order to prepare the complex drug release system, the loaded particles IB-MSNs were dispersed in chitosan solution and then the complex IB-MSNs/chitosan film of 2mm thickness was deposited as a hydrogel on the titanium electrode. The codeposition of components was performed under a negative biasing of the titanium electrode at -0.75 mA/cm2 current density during 30 min. The IB release from the IB-MSNs/chitosan hydrogel film was studied as dependent on pH of the release media and electrical conditions applied to the titanium plate. When incubating the complex hydrogel film in buffers with different pH, the IB release followed a near zero-order profile, though its kinetics varied. Compared to the spontaneous IB release from the hydrogel in 0.9% NaCl solution (at 0 V), the application of negative biases to the coated titanium plate had profound effluences on the release behavior. The release was retarded when -1.0 V was applied, but a faster kinetics was observed at -5.0 V. These results imply that a rapid, mild and facile electrical process for covering titanium implants by complex IB-MSNs/chitosan hydrogel films can be used for controlled drug delivery applications.

  5. The release characteristics of a model protein from self-assembled succinimide-terminated poly(lactide-co-glycolide ethylene oxide fumarate) nanoparticles

    NASA Astrophysics Data System (ADS)

    Mercado, Angel E.; He, Xuezhong; Xu, Weijie; Jabbari, Esmaiel

    2008-08-01

    Lactide-co-glycolide-based functionalized nanoparticles (NPs), because of their high surface areas for conjugation and biodegradability, are attractive as carriers for stabilization and sustained delivery of therapeutic agents and protein drugs. The objective of this work was to compare the release characteristics of model molecules encapsulated in NPs produced from poly(lactide-co-glycolide fumarate) (PLGF) macromer with those of model molecules conjugated to NPs produced from succinimide (NHS)-terminated PLGF-NHS macromer. Poly(lactide fumarate) (PLAF), PLGF and poly(lactide-co-ethylene oxide fumarate) (PLEOF) macromers were synthesized by condensation polymerization. The hydroxyl end-groups of PLAF and PLGF macromers were reacted with N,N'-disuccinimidyl carbonate (DSC) to produce succinimide-terminated PLAF-NHS and PLGF-NHS macromers. The macromers were self-assembled by dialysis to form NPs. The amphiphilic PLEOF macromer was used as the surfactant to stabilize the NPs in the process of self-assembly. 1-(2-pyridylazo)-2-naphthol (PAN) was used as a model small molecule for encapsulation in PLAF or PLGF NPs and bovine serum albumin (BSA) was used as a model protein for conjugation to PLAF-NHS and PLGF-NHS NPs. The profile of release of the encapsulated PAN from PLAF and PLGF NPs was non-linear and consisted of a burst release followed by a period of sustained release. The release profile for BSA, conjugated to PLAF-NHS and PLGF-NHS NPs, was linear up to complete degradation of the NPs. PLGF and PLAF NPs degraded in 15 and 28 days, respectively, while PLGF-NHS and PLAF-NHS NPs degraded in 25 and 38 days, which demonstrated that the release was dominated by erosion of the matrix. PLAF-NHS and PLGF-NHS NPs are potentially useful as carriers for sustained in situ release of protein drugs.

  6. Targeted delivery and pH-responsive release of stereoisomeric anti-cancer drugs using β-cyclodextrin assemblied Fe3O4 nanoparticles

    NASA Astrophysics Data System (ADS)

    Wang, Congli; Huang, Lizhen; Song, Shengmei; Saif, Bassam; Zhou, Yehong; Dong, Chuan; Shuang, Shaomin

    2015-12-01

    The β-cyclodextrin assemblied magnetic Fe3O4 nanoparticles (β-CD-MNPs) were successfully fabricated via a layer-by-layer method. Possessing an average size 14 nm, good stability and super-paramagnetic response (Ms 64 emu/g), the resultant nanocomposites could be served as a versatile biocompatible platform for selective loading, targeted delivery and pH-responsive release of stereoisomeric doxorubicin (DOX) and epirubicin (EPI). 1H-nuclear magnetic resonance (1H NMR) and the computer simulation further give the evidence that partial anthracene ring of drug molecule is included by β-CD. In addition, non-toxic β-CD-MNPs have excellent biocompatibility on MCF-7 cells, and cellular uptake indicate that different amounts of DOX or EPI can be transported to targeting site and released from the internalized carriers. The results demonstrate that as-prepared β-CD-MNPs could be a very promising vehicle for DOX and EPI.

  7. Layer-by-Layer Assembled Milk Protein Coated Magnetic Nanoparticle Enabled Oral Drug Delivery with High Stability in Stomach and Enzyme-Responsive Release in Small Intestine

    PubMed Central

    Huang, Jing; Shu, Qing; Wang, Liya; Wu, Hui; Wang, Andrew Y.; Mao, Hui

    2014-01-01

    We report a novel drug delivery system composed of layer-by-layer (LBL) milk protein casein (CN) coated iron oxide nanoparticles. Doxorubicin (DOX) and indocyanine green (ICG) were selected as model drug molecules, which were incorporated into the inner polymeric layer, and subsequently coated with casein. The resulting casein coated iron oxide nanoparticles (CN-DOX/ICG-IO) were stable in the acidic gastric condition with the presence of gastric protease. On the other hand, the loaded drugs were released when the casein outer layer was gradually degraded by the intestinal protease in the simulated intestine condition. Such unique properties enable maintenance of the bioactivity of the drugs and thus enhance the drug delivery efficiency. Ex vivo experiments showed that the LBL CN-DOX-IO improved the translocation of DOX across microvilli and its absorption in the small intestine sacs. In vivo imaging of mice that were orally administered with these LBL CN-ICG-IO nanostructures further confirmed that the reported drug delivery vehicles could pass the stomach without significant degradation, and then accumulated in the small intestine. In addition, the magnetic iron oxide nanoparticle core offered an MRI contrast enhancing capability for in vivo imaging guided drug delivery. Therefore, the reported LBL CN-DOX/ICG-IO is a promising oral drug delivery nanoplatform, especially for drugs that are poorly soluble in water or degradable in the gastric environment. PMID:25477177

  8. Towards the controlled release of metal nanoparticles from biomaterials: Physico-chemical, morphological and bioactivity features of Cu-containing sol-gel glasses

    NASA Astrophysics Data System (ADS)

    Aina, Valentina; Cerrato, Giuseppina; Martra, Gianmario; Malavasi, Gianluca; Lusvardi, Gigliola; Menabue, Ledi

    2013-10-01

    Two Cu-containing bioactive glasses were prepared and characterized in order to obtain a detailed description of chemical, morphological and bioactivity proprieties of potential Cu releasing systems. The characterization has demonstrated that by varying the synthesis procedure is possible to obtain two systems with Cu species in two different oxidation states and aggregation: (i) SGCu(ox) - oxidated Cu - (Cu oxidation state +2) homogeneously dispersed in the glass network matrix and (ii) SGCu(red) - metallic Cu - (Cu oxidation state 0) containing nano-particles (5-130 nm range) mainly present on the glass surface. The introduction of Cu maintains the bioactivity of the Cu-containing glasses almost unchanged, inducing a partial delay in the hydroxyapatite/hydroxy-carbonate apatite (HA/HCA) formation on the glass surface with respect to the reference glass (free Cu glass). During the bioactivity test, Cu is released from both Cu-containing glasses, in particular in the case of the SGCu(red) the presence of Cu nanoparticles (CuNPs) of diameter in the range 5-10 nm has been detected in solution.

  9. Release Behavior and Toxicity Profiles towards Leukemia (WEHI-3B) Cell Lines of 6-Mercaptopurine-PEG-Coated Magnetite Nanoparticles Delivery System

    PubMed Central

    Kura, Aminu Umar; Hussein-Al-Ali, Samer Hasan; Hussein, Mohd Zobir bin; Fakurazi, Sharida; Shaari, Abdul Halim; Ahmad, Zalinah

    2014-01-01

    The coating of an active drug, 6-mercaptopurine, into the iron oxide nanoparticles-polyethylene glycol (FNPs-PEG) in order to form a new nanocomposite, FPEGMP-2, was accomplished using coprecipitation technique. The resulting nanosized with a narrow size distribution magnetic polymeric particles show the superparamagnetic properties with 38.6 emu/g saturation magnetization at room temperature. Fourier transform infrared spectroscopy and the thermal analysis study supported the formation of the nanocomposite and the enhancement of thermal stability in the resulting nanocomposite comparing with its counterpart in free state. The loading of 6-mercaptopurine (MP) in the FPEGMP-2 nanocomposite was estimated to be about 5.6% and the kinetic experimental data properly correlated with the pseudo-second order model. Also, the release of MP from the FPEGMP-2 nanocomposite shows the sustained release manner which is remarkably lower in phosphate buffered solution at pH 7.4 than pH 4.8, due to different release mechanism. The maximum percentage release of MP from the nanocomposite reached about 60% and 97% within about 92 and 74 hours when exposed to pH 7.4 and 4.8, respectively. PMID:24895684

  10. DNA-mediated construction of hollow upconversion nanoparticles for protein harvesting and near-infrared light triggered release.

    PubMed

    Zhou, Li; Chen, Zhaowei; Dong, Kai; Yin, Meili; Ren, Jinsong; Qu, Xiaogang

    2014-04-16

    A simple DNA-mediated solvothermal method has been developed for the construction of well-defined hollow UNPs that can be used for a new paradigm to realize NIR light-controlled non-invasive protein release. In vitro studies show that the UNPs are capable of the transportation of enzyme into living cells. Intracellular NIR triggers the release of enzymes with high spatial and temporal precision and the released enzyme also retains its biological activity.

  11. Cytotoxicity and cytokine release in rat hepatocytes, C3A cells and macrophages exposed to gold nanoparticles--effect of biological dispersion media or corona.

    PubMed

    Brown, David M; Johnston, Helinor; Gubbins, Eva; Stone, Vicki

    2014-11-01

    The study aim was to investigate how gold nanoparticles (NPs) of different sizes (20 and 100 nm) influence primary hepatocytes, the hepatocyte cell line C3A and macrophage cytokine responses when dispersed in lung or blood relevant fluids. Gold Au NPs induced cytotoxicity in primary hepatocytes at the highest dose of 66 μg/cm2, this effect was modified by the dispersant, the effect was greater with lung lining fluid (LLF). Release of interleukin (IL)-6, Monocyte chemoattractant protein-1 (MCP-1) and IL-1β was enhanced by the Au NPs and the effects were influenced by the particle size and dispersant. In medium, the smallest particle size was most effective at inducing IL-6 release, while in LLF the largest particles were most effective at inducing IL-6 release. Both 20 nm and 100 nm particles enhanced MCP-1 and IL-1β in the presence of LLF. The Au particles had no cytotoxic effects nor did they stimulate the release of cytokines in the C3A hepatoma cell line. The Au NPs had no significant impact on macrophage viability. Particles induced IL-6 and TNF-α release. LLF and serum reduced the IL-6 response while albumin enhanced the TNF-α response compared to medium dispersed Au NPs. The Au NPs did not impact on MCP-1 release, but this cytokine was enhanced by albumin and serum, while it was depressed by LLF. The macrophage responses were lower than those evoked in primary hepatocytes. In conclusion, when assessing the cytotoxic and pro-inflammatory responses induced by Au NPs, the response is influenced by the dispersant, with different dispersants having different effects in different cell types. PMID:26000400

  12. Self-carried curcumin nanoparticles for in vitro and in vivo cancer therapy with real-time monitoring of drug release

    NASA Astrophysics Data System (ADS)

    Zhang, Jinfeng; Li, Shengliang; An, Fei-Fei; Liu, Juan; Jin, Shubin; Zhang, Jin-Chao; Wang, Paul C.; Zhang, Xiaohong; Lee, Chun-Sing; Liang, Xing-Jie

    2015-08-01

    The use of different nanocarriers for delivering hydrophobic pharmaceutical agents to tumor sites has garnered major attention. Despite the merits of these nanocarriers, further studies are needed to improve their drug loading capacities (which are typically <10%) and reduce their potential systemic toxicity. Therefore, the development of alternative self-carried nanodrug delivery strategies without using inert carriers is highly desirable. In this study, we developed a self-carried curcumin (Cur) nanodrug for highly effective cancer therapy in vitro and in vivo with real-time monitoring of drug release. With a biocompatible C18PMH-PEG functionalization, the Cur nanoparticles (NPs) showed excellent dispersibility and outstanding stability in physiological environments with drug loading capacities >78 wt%. Both confocal microscopy and flow cytometry confirmed the cellular fluorescence ``OFF-ON'' activation and real-time monitoring of the Cur molecule release. In vitro and in vivo experiments clearly show that the therapeutic efficacy of the PEGylated Cur NPs is considerably better than that of free Cur. This self-carried strategy with real-time monitoring of drug release may open a new way for simultaneous cancer therapy and monitoring.The use of different nanocarriers for delivering hydrophobic pharmaceutical agents to tumor sites has garnered major attention. Despite the merits of these nanocarriers, further studies are needed to improve their drug loading capacities (which are typically <10%) and reduce their potential systemic toxicity. Therefore, the development of alternative self-carried nanodrug delivery strategies without using inert carriers is highly desirable. In this study, we developed a self-carried curcumin (Cur) nanodrug for highly effective cancer therapy in vitro and in vivo with real-time monitoring of drug release. With a biocompatible C18PMH-PEG functionalization, the Cur nanoparticles (NPs) showed excellent dispersibility and outstanding

  13. Release of Phosphorous Impurity from TiO2 Anatase and Rutile Nanoparticles in Aquatic Environments and Its Implications

    EPA Science Inventory

    Phosphorus-bearing materials as an additive have been popularly used in nanomaterial synthesis and the residual phosphorus within the nanoparticles (NPs) can be of an environmental concern. For instance, phosphorus within pristine commercial TiO2 NPs greatly influences the surfac...

  14. Exposure-dependent Ag+ release from silver nanoparticles and its complexation in AgS2 sites in primary murine macrophages

    NASA Astrophysics Data System (ADS)

    Veronesi, G.; Aude-Garcia, C.; Kieffer, I.; Gallon, T.; Delangle, P.; Herlin-Boime, N.; Rabilloud, T.; Carrière, M.

    2015-04-01

    Silver nanoparticle (AgNP) toxicity is related to their dissolution in biological environments and to the binding of the released Ag+ ions in cellulo; the chemical environment of recombined Ag+ ions is responsible for their toxicological outcome, moreover it is indicative of the cellular response to AgNP exposure, and can therefore shed light on the mechanisms governing AgNP toxicity. This study probes the chemistry of Ag species in primary murine macrophages exposed to AgNPs by making use of X-ray Absorption Fine Structure spectroscopy under cryogenic conditions: the linear combination analysis of the near-edge region of the spectra provides the fraction of Ag+ ions released from the AgNPs under a given exposure condition and highlights their complexation with thiolate groups; the ab initio modelling of the extended spectra allows measuring the Ag-S bond length in cellulo. Dissolution rates depend on the exposure scenario, chronicity leading to higher Ag+ release than acute exposure; Ag-S bond lengths are 2.41 +/- 0.03 Å and 2.38 +/- 0.01 Å in acute and chronic exposure respectively, compatible with digonal AgS2 coordination. Glutathione is identified as the most likely putative ligand for Ag+. The proposed method offers a scope for the investigation of metallic nanoparticle dissolution and recombination in cellular models.Silver nanoparticle (AgNP) toxicity is related to their dissolution in biological environments and to the binding of the released Ag+ ions in cellulo; the chemical environment of recombined Ag+ ions is responsible for their toxicological outcome, moreover it is indicative of the cellular response to AgNP exposure, and can therefore shed light on the mechanisms governing AgNP toxicity. This study probes the chemistry of Ag species in primary murine macrophages exposed to AgNPs by making use of X-ray Absorption Fine Structure spectroscopy under cryogenic conditions: the linear combination analysis of the near-edge region of the spectra provides

  15. Rational design on controlled release ion-exchange polymeric microspheres and polymer-lipid hybrid nanoparticles for the delivery of water-soluble drugs through a multidisciplinary approach

    NASA Astrophysics Data System (ADS)

    Li, Yongqiang

    Sulfopropyl dextran sulfate (SP-DS) microspheres and polymer-lipid hybrid nanoparticles (PLN) for the delivery of water-soluble anticancer drugs and P-glycoprotein inhibitors were developed by our group recently and demonstrated effectiveness in local chemotherapy. To optimize the delivery performance of these particulate systems, particularly PLN, an integrated multidisciplinary approach was developed, based on an in-depth understanding of drug-excipient interactions, internal structure, drug loading and release mechanisms, and application of advanced modeling/optimization techniques. An artificial neural networks (ANN) simulator capable of formulation optimization and drug release prediction was developed. In vitro drug release kinetics of SP-DS microspheres, with various drug loading and in different release media, were predicted by ANN. The effects of independent variables on drug release were evaluated. Good modeling performance suggested that ANN is a useful tool to predict drug release from ion-exchange microspheres. To further improve the performance of PLN, drug-polymer-lipid interactions were characterized theoretically and experimentally using verapamil hydrochloride (VRP) as a model drug and dextran sulfate sodium (DS) as a counter-ion polymer. VRP-DS complexation followed a stoichiometric rule and solid-state transformation of VRP were observed. Dodecanoic acid (DA) was identified as the lead lipid carrier material. Based upon the optimized drug-polymer-lipid interactions, PLN with high drug loading capacity (36%, w/w) and sustained release without initial burst release were achieved. VRP remained amorphous and was molecularly dispersed within PLN. H-bonding contributed to the miscibility between the VRP-DS complex and DA. Drug release from PLN was mainly controlled by diffusion and ion-exchange processes. Drug loading capacity and particle size of PLN depend on the formulation factors of the weight ratio of drug to lipid and concentrations of

  16. Inventory of Engineered Nanoparticle-Containing Consumer Products Available in the Singapore Retail Market and Likelihood of Release into the Aquatic Environment.

    PubMed

    Zhang, Yuanyuan; Leu, Yu-Rui; Aitken, Robert J; Riediker, Michael

    2015-08-01

    Consumer products containing engineered nanoparticles (ENP) are already entering the marketplace. This leads, inter alia, to questions about the potential for release of ENP into the environment from commercial products. We have inventoried the prevalence of ENP-containing consumer products in the Singapore market by carrying out onsite assessments of products sold in all major chains of retail and cosmetic stores. We have assessed their usage patterns and estimated release factors and emission quantities to obtain a better understanding of the quantities of ENP that are released into which compartments of the aquatic environment in Singapore. Products investigated were assessed for their likelihood to contain ENP based on the declaration of ENP by producers, feature descriptions, and the information on particle size from the literature. Among the 1,432 products investigated, 138 were "confirmed" and 293 were "likely" to contain ENP. Product categories included sunscreens, cosmetics, health and fitness, automotive, food, home and garden, clothing and footwear, and eyeglass/lens coatings. Among the 27 different types of nanomaterials identified, SiO2 was predominant, followed by TiO2 and ZnO, Carbon Black, Ag, and Au. The amounts of ENP released into the aquatic system, which was estimated on the basis of typical product use, ENP concentration in the product, daily use quantity, release factor, and market share, were in the range of several hundred tons per year. As these quantities are likely to increase, it will be important to further study the fate of ENP that reach the aquatic environment in Singapore. PMID:26213957

  17. Inventory of Engineered Nanoparticle-Containing Consumer Products Available in the Singapore Retail Market and Likelihood of Release into the Aquatic Environment

    PubMed Central

    Zhang, Yuanyuan; Leu, Yu-Rui; Aitken, Robert J.; Riediker, Michael

    2015-01-01

    Consumer products containing engineered nanoparticles (ENP) are already entering the marketplace. This leads, inter alia, to questions about the potential for release of ENP into the environment from commercial products. We have inventoried the prevalence of ENP-containing consumer products in the Singapore market by carrying out onsite assessments of products sold in all major chains of retail and cosmetic stores. We have assessed their usage patterns and estimated release factors and emission quantities to obtain a better understanding of the quantities of ENP that are released into which compartments of the aquatic environment in Singapore. Products investigated were assessed for their likelihood to contain ENP based on the declaration of ENP by producers, feature descriptions, and the information on particle size from the literature. Among the 1,432 products investigated, 138 were “confirmed” and 293 were “likely” to contain ENP. Product categories included sunscreens, cosmetics, health and fitness, automotive, food, home and garden, clothing and footwear, and eyeglass/lens coatings. Among the 27 different types of nanomaterials identified, SiO2 was predominant, followed by TiO2 and ZnO, Carbon Black, Ag, and Au. The amounts of ENP released into the aquatic system, which was estimated on the basis of typical product use, ENP concentration in the product, daily use quantity, release factor, and market share, were in the range of several hundred tons per year. As these quantities are likely to increase, it will be important to further study the fate of ENP that reach the aquatic environment in Singapore. PMID:26213957

  18. Inventory of Engineered Nanoparticle-Containing Consumer Products Available in the Singapore Retail Market and Likelihood of Release into the Aquatic Environment.

    PubMed

    Zhang, Yuanyuan; Leu, Yu-Rui; Aitken, Robert J; Riediker, Michael

    2015-07-24

    Consumer products containing engineered nanoparticles (ENP) are already entering the marketplace. This leads, inter alia, to questions about the potential for release of ENP into the environment from commercial products. We have inventoried the prevalence of ENP-containing consumer products in the Singapore market by carrying out onsite assessments of products sold in all major chains of retail and cosmetic stores. We have assessed their usage patterns and estimated release factors and emission quantities to obtain a better understanding of the quantities of ENP that are released into which compartments of the aquatic environment in Singapore. Products investigated were assessed for their likelihood to contain ENP based on the declaration of ENP by producers, feature descriptions, and the information on particle size from the literature. Among the 1,432 products investigated, 138 were "confirmed" and 293 were "likely" to contain ENP. Product categories included sunscreens, cosmetics, health and fitness, automotive, food, home and garden, clothing and footwear, and eyeglass/lens coatings. Among the 27 different types of nanomaterials identified, SiO2 was predominant, followed by TiO2 and ZnO, Carbon Black, Ag, and Au. The amounts of ENP released into the aquatic system, which was estimated on the basis of typical product use, ENP concentration in the product, daily use quantity, release factor, and market share, were in the range of several hundred tons per year. As these quantities are likely to increase, it will be important to further study the fate of ENP that reach the aquatic environment in Singapore.

  19. Facile synthesis of magnetic-/pH-responsive hydrogel beads based on Fe3O4 nanoparticles and chitosan hydrogel as MTX carriers for controlled drug release.

    PubMed

    Wu, Juan; Jiang, Wei; Tian, Renbing; Shen, Yewen; Jiang, Wei

    2016-10-01

    In the present study, methotrexate (MTX)-encapsulated magnetic-/pH-responsive hydrogel beads based on Fe3O4 nanoparticles and chitosan were successfully prepared through a one-step gelation process, which is a very facile, economic and environmentally friendly route. The developed hydrogel beads exhibited homogeneous porous structure and super-paramagnetic responsibility. MTX can be successfully encapsulated into magnetic chitosan hydrogel beads, and the drug encapsulation efficiency (%) and encapsulation content (%) were 93.8 and 6.28%, respectively. In addition, the drug release studies in vitro indicated that the MTX-encapsulated magnetic chitosan hydrogel beads had excellent pH-sensitivity, 90.6% MTX was released from the magnetic chitosan hydrogel beads within 48 h at pH 4.0. WST-1 assays in human liver hepatocellular carcinoma cells (HepG2) demonstrated that the MTX-encapsulated magnetic chitosan hydrogel beads had good cytocompatibility and high anti-tumor activity. Therefore, our results revealed that the MTX-encapsulated magnetic chitosan hydrogel beads would be a competitive candidate for controlled drug release in the area of targeted cancer therapy in the near future.

  20. Facile synthesis of magnetic-/pH-responsive hydrogel beads based on Fe3O4 nanoparticles and chitosan hydrogel as MTX carriers for controlled drug release.

    PubMed

    Wu, Juan; Jiang, Wei; Tian, Renbing; Shen, Yewen; Jiang, Wei

    2016-10-01

    In the present study, methotrexate (MTX)-encapsulated magnetic-/pH-responsive hydrogel beads based on Fe3O4 nanoparticles and chitosan were successfully prepared through a one-step gelation process, which is a very facile, economic and environmentally friendly route. The developed hydrogel beads exhibited homogeneous porous structure and super-paramagnetic responsibility. MTX can be successfully encapsulated into magnetic chitosan hydrogel beads, and the drug encapsulation efficiency (%) and encapsulation content (%) were 93.8 and 6.28%, respectively. In addition, the drug release studies in vitro indicated that the MTX-encapsulated magnetic chitosan hydrogel beads had excellent pH-sensitivity, 90.6% MTX was released from the magnetic chitosan hydrogel beads within 48 h at pH 4.0. WST-1 assays in human liver hepatocellular carcinoma cells (HepG2) demonstrated that the MTX-encapsulated magnetic chitosan hydrogel beads had good cytocompatibility and high anti-tumor activity. Therefore, our results revealed that the MTX-encapsulated magnetic chitosan hydrogel beads would be a competitive candidate for controlled drug release in the area of targeted cancer therapy in the near future. PMID:27464586

  1. Embedding fluorescent mesoporous silica nanoparticles into biocompatible nanogels for tumor cell imaging and thermo/pH-sensitive in vitro drug release.

    PubMed

    Gui, Rijun; Wang, Yanfeng; Sun, Jie

    2014-04-01

    Thermo/pH-sensitive/fluorescent/biocompatible nanospheres consisting of quantum dots-embedded mesoporous silica nanoparticles (Q-MS) as a core and poly(N-isopropylacrylamide (NIPAM))-graft-chitosan (CS) nanogels as a shell (PNIPAM-g-CS) were prepared via temperature-regulated one-pot copolymerization of NIPAM monomer and CS in the presence of Q-MS. The prepared nanospheres exhibited remarkable fluorescence/thermo/pH-sensitivity. HepG2 cells treated with nanospheres displayed bright fluorescence imaging. Loading efficiency and capacity of Doxorubicin (Dox) into nanospheres were regularly increased with the increment of Dox concentration. At a high temperature and a low pH, cumulative in vitro release of Dox from Dox-loaded nanospheres was much great and fast. Released Dox still retained high anticancer activity, and blank nanosphere carriers produced neglectful toxicity to HepG2 cells. The multifunctional nanospheres could be further developed toward temperature/pH-regulated drug carriers for in vivo tumor therapy with a rapid drug release and fluorescence imaging in targeted tissues.

  2. Beyond platinum: synthesis, characterization, and in vitro toxicity of Cu(II)-releasing polymer nanoparticles for potential use as a drug delivery vector

    NASA Astrophysics Data System (ADS)

    Harris, Alesha N.; Hinojosa, Barbara R.; Chavious, Montaleé D.; Petros, Robby A.

    2011-07-01

    The field of drug delivery focuses primarily on delivering small organic molecules or DNA/RNA as therapeutics and has largely ignored the potential for delivering catalytically active transition metal ions and complexes. The delivery of a variety of transition metals has potential for inducing apoptosis in targeted cells. The chief aims of this work were the development of a suitable delivery vector for a prototypical transition metal, Cu2+, and demonstration of the ability to impact cancer cell viability via exposure to such a Cu-loaded vector. Carboxylate-functionalized nanoparticles were synthesized by free radical polymerization and were subsequently loaded with Cu2+ via binding to particle-bound carboxylate functional groups. Cu loading and release were characterized via ICP MS, EDX, XPS, and elemental analysis. Results demonstrated that Cu could be loaded in high weight percent (up to 16 wt.%) and that Cu was released from the particles in a pH-dependent manner. Metal release was a function of both pH and the presence of competing ligands. The toxicity of the particles was measured in HeLa cells where reductions in cell viability greater than 95% were observed at high Cu loading. The combined pH sensitivity and significant toxicity make this copper delivery vector an excellent candidate for the targeted killing of disease cells when combined with an effective cellular targeting strategy.

  3. Deposition and Release Behaviour of ZnO Nanoparticles in Saturated Quartz Sand: Role of Biofilm, Ionic Strength, and pH

    NASA Astrophysics Data System (ADS)

    Hwang, Gukhwa; Han, Yosep; Kim, Donghyun; Bradford, Scott A.; Lee, Byoungcheun; Eom, Igchun; Kim, Pil Je; Choi, Siyoung Q.; Lee, Youngsoo; Kim, Hyunjung

    2015-04-01

    The influence of biofilm, ionic strength, and pH on the deposition and release behavior of zinc oxide nanoparticles (ZnO-NPs) was systematically investigated in well-controlled saturated sand column. The results for the initial transport of the ZnO-NPs at pH 9 showed significant retention at the inlet of the column with hyper-exponential retention profiles regardless of solution ionic strength investigated (0.1 and 10 mM) and Pseudomonas putida biofilm coating; however, the increase in solution ionic strength and the presence of biofilm onto quartz sand tended to increase the retention of ZnO-NPs. The trend was likely attributed to more favorable NPs-NPs interaction and greater surface roughness, respectively. The results were well supported by the DLVO interaction energy profiles and Electron Microscopic observations. For the release tests, particle free solution at pH 6 was continuously injected into the column with the ZnO-NPs retained during the initial transport tests. The results for breakthrough curves and time-lapsed retention profiles showed that reducing solution pH led to the release of large amount of the initially retained ZnO-NPs, and the release rate was observed to be greater for bare silica than biofilm-coated sand. The release of ZnO-NPs was likely attributed to the dissolution of Zn2+ due to the change of pH. The proposed mechanism was further verified by conducting additional column tests at higher pHs (pH 9 and 10), which showed significantly reduced release of ZnO-NPs, and even nearly no release at pH 10. The findings from this study suggests that there exists high potential of complete transport of ZnO-NPs into groundwater in that the pH of various soil environments typically ranges from 5 to 9. This work was supported by the National Institute of Environmental Research, Ministry of Environment and the Energy Efficiency & Resources Core Technology Program of the Korea Institute of Energy Technology Evaluation and Planning (KETEP), granted

  4. Loading of Silica Nanoparticles in Block Copolymer Vesicles during Polymerization-Induced Self-Assembly: Encapsulation Efficiency and Thermally Triggered Release.

    PubMed

    Mable, Charlotte J; Gibson, Rebecca R; Prevost, Sylvain; McKenzie, Beulah E; Mykhaylyk, Oleksandr O; Armes, Steven P

    2015-12-30

    Poly(glycerol monomethacrylate)-poly(2-hydroxypropyl methacrylate) diblock copolymer vesicles can be prepared in the form of concentrated aqueous dispersions via polymerization-induced self-assembly (PISA). In the present study, these syntheses are conducted in the presence of varying amounts of silica nanoparticles of approximately 18 nm diameter. This approach leads to encapsulation of up to hundreds of silica nanoparticles per vesicle. Silica has high electron contrast compared to the copolymer which facilitates TEM analysis, and its thermal stability enables quantification of the loading efficiency via thermogravimetric analysis. Encapsulation efficiencies can be calculated using disk centrifuge photosedimentometry, since the vesicle density increases at higher silica loadings while the mean vesicle diameter remains essentially unchanged. Small angle X-ray scattering (SAXS) is used to confirm silica encapsulation, since a structure factor is observed at q ≈ 0.25 nm(-1). A new two-population model provides satisfactory data fits to the SAXS patterns and allows the mean silica volume fraction within the vesicles to be determined. Finally, the thermoresponsive nature of the diblock copolymer vesicles enables thermally triggered release of the encapsulated silica nanoparticles simply by cooling to 0-10 °C, which induces a morphological transition. These silica-loaded vesicles constitute a useful model system for understanding the encapsulation of globular proteins, enzymes, or antibodies for potential biomedical applications. They may also serve as an active payload for self-healing hydrogels or repair of biological tissue. Finally, we also encapsulate a model globular protein, bovine serum albumin, and calculate its loading efficiency using fluorescence spectroscopy. PMID:26600089

  5. Phytotoxicity of ZnO nanoparticles and the released Zn(II) ion to corn (Zea mays L.) and cucumber (Cucumis sativus L.) during germination.

    PubMed

    Zhang, Ruichang; Zhang, Haibo; Tu, Chen; Hu, Xuefeng; Li, Lianzhen; Luo, Yongming; Christie, Peter

    2015-07-01

    Toxicity of engineered nanoparticles on organisms is of concern worldwide due to their extensive use and unique properties. The impacts of ZnO nanoparticles (ZnO NPs) on seed germination and root elongation of corn (Zea mays L.) and cucumber (Cucumis sativus L.) were investigated in this study. The role of seed coats of corn in the mitigation toxicity of nanoparticles was also evaluated. ZnO NPs (1,000 mg L(-1)) reduced root length of corn and cucumber by 17 % (p < 0.05) and 51 % (p < 0.05), respectively, but exhibited no effects on germination. In comparison with Zn(2+), toxicity of ZnO NPs on the root elongation of corn could be attributed to the nanoparticulate ZnO, while released Zn ion from ZnO could solely contribute to the inhibition of root elongation of cucumber. Zn uptake in corn exposed to ZnO NPs during germination was much higher than that in corn exposed to Zn(2+), whereas Zn uptake in cucumber was significantly correlated with soluble Zn in suspension. It could be inferred that Zn was taken up by corn and cucumber mainly in the form of ZnO NPs and soluble Zn, respectively. Transmission electron microscope confirmed the uptake of ZnO NPs into root of corn. Although isolation of the seed coats might not be the principal factor that achieved avoidance from toxicity on germination, seed coats of corn were found to mitigate the toxicity of ZnO NPs on root elongation and prevent approximately half of the Zn from entering into root and endosperm.

  6. The antimicrobial efficacy of sustained release silver–carbene complex-loaded l-tyrosine polyphosphate nanoparticles: Characterization, in vitro and in vivo studies

    PubMed Central

    Hindi, Khadijah M.; Ditto, Andrew J.; Panzner, Matthew J.; Medvetz, Douglas A.; Han, Daniel S.; Hovis, Christine E.; Hilliard, Julia K.; Taylor, Jane B.; Yun, Yang H.; Cannon, Carolyn L.; Youngs, Wiley J.

    2009-01-01

    The pressing need to treat multi-drug resistant bacteria in the chronically infected lungs of cystic fibrosis (CF) patients has given rise to novel nebulized antimicrobials. We have synthesized a silver–carbene complex (SCC10) active against a variety of bacterial strains associated with CF and chronic lung infections. Our studies have demonstrated that SCC10-loaded into l-tyrosine polyphosphate nanoparticles (LTP NPs) exhibits excellent antimicrobial activity in vitro and in vivo against the CF relevant bacteria Pseudomonas aeruginosa. Encapsulation of SCC10 in LTP NPs provides sustained release of the antimicrobial over the course of several days translating into efficacious results in vivo with only two administered doses over a 72 h period. PMID:19395021

  7. Challenge to assess the toxic contribution of metal cation released from nanomaterials for nanotoxicology - the case of ZnO nanoparticles

    NASA Astrophysics Data System (ADS)

    Xu, Mingsheng; Li, Jie; Hanagata, Nobutaka; Su, Huanxing; Chen, Hongzheng; Fujita, Daisuke

    2013-05-01

    The identification of physicochemical factors that govern toxic effects of nanomaterials (NMs) is important for the safe design and synthesis of NMs. The release of metal cations from NMs in cell culture medium and the role of the metal cations in cytotoxicity are still under dispute. Here, we report that removal of NMs such as ZnO nanoparticles (NPs) by centrifugation, the procedure commonly used for the estimation of released ion concentration in nanotoxicology, was incomplete even at a relative centrifugal force of 150 000 × g. In this sense, the Zn concentration in supernatant measured by inductively coupled plasma-mass spectrometry cannot be regarded as the concentration of free Zn2+ ions which were released from ZnO NPs in cell culture medium. This suggests the urgent need to develop relevant analytical techniques for nanotoxicology. The toxic contribution of released Zn2+ ions to the A549 cell lines was estimated to be only about 10%. We conclude that the cytotoxicity associated with ZnO NPs is not a function of the Zn concentration, suggesting that other factors play an important role in the toxic effect of ZnO NPs.The identification of physicochemical factors that govern toxic effects of nanomaterials (NMs) is important for the safe design and synthesis of NMs. The release of metal cations from NMs in cell culture medium and the role of the metal cations in cytotoxicity are still under dispute. Here, we report that removal of NMs such as ZnO nanoparticles (NPs) by centrifugation, the procedure commonly used for the estimation of released ion concentration in nanotoxicology, was incomplete even at a relative centrifugal force of 150 000 × g. In this sense, the Zn concentration in supernatant measured by inductively coupled plasma-mass spectrometry cannot be regarded as the concentration of free Zn2+ ions which were released from ZnO NPs in cell culture medium. This suggests the urgent need to develop relevant analytical techniques for nanotoxicology. The

  8. Increase of the duration of the anticonvulsive activity of a novel NMDA receptor antagonist using poly(butylcyanoacrylate) nanoparticles as a parenteral controlled release system.

    PubMed

    Friese, A; Seiller, E; Quack, G; Lorenz, B; Kreuter, J

    2000-03-01

    A novel non-competitive NMDA receptor antagonist MRZ 2/576 is a potent but rather short-acting (5-15 min) anticonvulsant following intravenous administration to mice as estimated by the prevention of maximal electroshock induced convulsions. This is most probably due to a rapid elimination of the drug from the central nervous system by transport processes that are sensitive to probenecid. Intravenous administration of the drug bound to poly(butylcyanoacrylate) nanoparticles coated with polysorbate 80 prolongs the duration of the anticonvulsive activity in mice up to 210 min and after probenecid pre-treatment up to 270 min compared to 150 min with probenecid and MRZ 2/576 alone. The results of this study demonstrate that polysorbate 80 coated poly(butylcyanoacrylate) nanoparticles used so far as a delivery system to the brain for drugs that do not freely penetrate the blood brain barrier can also be used as a parenteral controlled release system to prolong the CNS availability of drugs that have a short duration of action.

  9. Magnetic Field-Induced Accentuation of Drug Release from Core/Shell Magnetic Mesoporous Silica Nanoparticles for Anticancer Treatment.

    PubMed

    Knezević Nikola Z

    2016-04-01

    Drug (9-aminoacridine) loaded core/shell magnetic iron oxide-containing mesoporous silica nanoparticles (MMSN) were treated with HeLa cells and the drug carriers were agitated by expo- sure to magnetic field. Viability studies show the applicability of drug loaded magnetic material for anticancer treatment, which is enhanced upon stimulation with magnetic field. Confocal micrographs of fluorescein grafted MMSN-treated HeLa cells confirmed the ability of magnetic field to concentrate the synthesized material in the exposed area of the cells. The synthesized material and the applied drug delivery method may find application in magnetic field-responsive targeted treatment of cancer. PMID:27451786

  10. Targeted radiotherapy enhancement during electronic brachytherapy of accelerated partial breast irradiation (APBI) using controlled release of gold nanoparticles.

    PubMed

    Cifter, G; Chin, J; Cifter, F; Altundal, Y; Sinha, N; Sajo, E; Ngwa, W

    2015-12-01

    Several studies have demonstrated low rates of local recurrence with brachytherapy-based accelerated partial breast irradiation (APBI). However, long-term outcomes on toxicity (e.g. telangiectasia) and cosmesis remain a major concern. The purpose of this study is to investigate the dosimetric feasibility of using targeted non-toxic radiosensitizing gold nanoparticles (GNPs) for localized dose enhancement to the planning target volume (PTV) during electronic brachytherapy APBI while reducing normal tissue toxicity. We propose to incorporate GNPs into a micrometer-thick polymer film on the surface of routinely used lumpectomy balloon applicators and provide subsequent treatment using a 50 kVp Xoft device. An experimentally determined diffusion coefficient was used to determine space-time customizable distribution of GNPs for feasible in-vivo concentrations of 7 mg/g and 43 mg/g. An analytical approach from previously published work was employed to estimate the dose enhancement due to GNPs as a function of distance up to 1 cm from the lumpectomy cavity surface. Clinically significant dose enhancement values of at least 1.2, due to 2 nm GNPs, were found at 1 cm away from the lumpectomy cavity wall when using electronic brachytherapy APBI. Higher customizable dose enhancement was also achieved at other distances as a function of nanoparticle size. Our preliminary results suggest that significant dose enhancement can be achieved to residual tumor cells targeted with GNPs during APBI with electronic brachytherapy.

  11. Palmitate Induces mRNA Translation and Increases ER Protein Load in Islet β-Cells via Activation of the Mammalian Target of Rapamycin Pathway

    PubMed Central

    Hatanaka, Masayuki; Maier, Bernhard; Sims, Emily K.; Templin, Andrew T.; Kulkarni, Rohit N.; Evans-Molina, Carmella

    2014-01-01

    Saturated free fatty acids (FFAs) have complex effects on the islet β-cell, acutely promoting adaptive hyperplasia but chronically impairing insulin release. The acute effects of FFAs remain incompletely defined. To elucidate these early molecular events, we incubated mouse β-cells and islets with palmitate and then studied mRNA translation by polyribosomal profiling and analyzed signaling pathways by immunoblot analysis. We found that palmitate acutely increases polyribosome occupancy of total RNA, consistent with an increase in mRNA translation. This effect on translation was attributable to activation of mammalian target of rapamycin (mTOR) pathways via L-type Ca2+ channels but was independent of insulin signaling. Longer incubations led to depletion of polyribosome-associated RNA, consistent with activation of the unfolded protein response (UPR). Pharmacologic inhibition of mTOR suppressed both the acute effects of palmitate on mRNA translation and the chronic effects on the UPR. Islets from mice fed a high-fat diet for 7 days showed increases in polyribosome-associated RNA and phosphorylation of S6K, both consistent with activation of mTOR. Our results suggest that palmitate acutely activates mRNA translation and that this increase in protein load contributes to the later UPR. PMID:24834975

  12. A Long-Acting BMP-2 Release System Based on Poly(3-hydroxybutyrate) Nanoparticles Modified by Amphiphilic Phospholipid for Osteogenic Differentiation

    PubMed Central

    Peng, Xiaochun; Chen, Yunsu; Li, Yamin; Wang, Yiming

    2016-01-01

    We explored a novel poly(3-hydroxybutyrate) (PHB) nanoparticle loaded with hydrophilic recombinant human BMP-2 with amphiphilic phospholipid (BPC-PHB NP) for a rapid-acting and long-acting delivery system of BMP-2 for osteogenic differentiation. The BPC-PHB NPs were prepared by a solvent evaporation method and showed a spherical particle with a mean particle size of 253.4 nm, mean zeta potential of −22.42 mV, and high entrapment efficiency of 77.18%, respectively. For BPC-PHB NPs, a short initial burst release of BMP-2 from NPs in 24 h was found and it has steadily risen to reach about 80% in 20 days for in vitro test. BPC-PHB NPs significantly reduced the burst release of BMP-2, as compared to that of PHB NPs loading BMP-2 without PL (B-PHB NPs). BPC-PHB NPs maintained the content of BMP-2 for a long-term osteogenic differentiation. The OCT-1 cells with BPC-PHB NPs have high ALP activity in comparison with others. The gene markers for osteogenic differentiation were significantly upregulated for sample with BPC-PHB NPs, implying that BPC-PHB NPs can be used as a rapid-acting and long-acting BMP-2 delivery system for osteogenic differentiation. PMID:27379249

  13. Responsive polymer-fluorescent carbon nanoparticle hybrid nanogels for optical temperature sensing, near-infrared light-responsive drug release, and tumor cell imaging.

    PubMed

    Wang, Hui; Ke, Fuyou; Mararenko, Anton; Wei, Zengyan; Banerjee, Probal; Zhou, Shuiqin

    2014-07-01

    Fluorescent carbon nanoparticles (FCNPs) have been successfully immobilized into poly(N-isopropylacrylamide-co-acrylamide) [poly(NIPAM-AAm)] nanogels based on one-pot precipitation copolymerization of NIPAM monomers with hydrogen bonded FCNP-AAm complex monomers in water. The resultant poly(NIPAM-AAm)-FCNP hybrid nanogels can combine functions from each building block for fluorescent temperature sensing, cell imaging, and near-infrared (NIR) light responsive drug delivery. The FCNPs in the hybrid nanogels not only emit bright and stable photoluminescence (PL) and exhibit up-conversion PL properties, but also increase the loading capacity of the nanogels for curcumin drug molecules. The reversible thermo-responsive swelling/shrinking transition of the poly(NIPAM-AAm) nanogel can not only modify the physicochemical environment of the FCNPs to manipulate the PL intensity for sensing the environmental temperature change, but also regulate the releasing rate of the loaded anticancer drug. In addition, the FCNPs embedded in the nanogels can convert the NIR light to heat, thus an exogenous NIR irradiation can further accelerate the drug release and enhance the therapeutic efficacy. The hybrid nanogels can overcome cellular barriers to enter the intracellular region and light up the mouse melanoma B16F10 cells upon laser excitation. The demonstrated hybrid nanogels with nontoxic and optically active FCNPs immobilized in responsive polymer nanogels are promising for the development of a new generation of multifunctional materials for biomedical applications.

  14. Tamoxifen-loaded nanoparticles based on a novel mixture of biodegradable polyesters: characterization and in vitro evaluation as sustained release systems.

    PubMed

    Pérez, Elena; Benito, Marta; Teijón, César; Olmo, Rosa; Teijón, José M; Blanco, M Dolores

    2012-01-01

    Nanoparticles (NP) from mixtures of two poly(D,L-lactide-co-caprolactone) (PLC) copolymers, PLC 40/60 and PLC 86/14, with poly(D,L-lactide) (PDLLA) and PCL were prepared: PLC 40/60-PCL (25:75), PLC 86/14-PCL (75:25) and PLC 86/14-PLA (75:25). Tamoxifen was loaded with encapsulation efficiency between 65% and 75% (29.9-36.3 µg TMX/ mg NP). All selected systems showed spherical shape and nano-scale size. TMX-loaded NPs were in the range of 293-352 nm. TMX release from NP took place with different profiles depending on polymeric composition of the particles. After 60 days, 59.81% and 82.65% of the loaded drug was released. The cytotoxicity of unloaded NP in MCF7 and HeLa cells was very low. Cell uptake of NP took place in both cell types by unspecific internalization in a time dependent process. The administration of 6 and 10 µm TMX by TMX-loaded NP was effective on both cellular types, mainly in MCF7 cells. PMID:22251238

  15. Controlled release matrices and micro/nanoparticles of chitosan with antimicrobial potential: development of new strategies for microbial control in agriculture.

    PubMed

    Cota-Arriola, Octavio; Cortez-Rocha, Mario Onofre; Burgos-Hernández, Armando; Ezquerra-Brauer, Josafat Marina; Plascencia-Jatomea, Maribel

    2013-05-01

    The control of micro-organisms responsible for pre- and postharvest diseases of agricultural products, mainly viruses and fungi, is a problem that remains unresolved, together with the environmental impact of the excessive use of chemicals to tackle this problem. Current efforts are focused on the search for efficient alternatives for microbial control that will not result in damage to the environment or an imbalance in the existing biota. One alternative is the use of natural antimicrobial compounds such as chitosan, a linear cationic biopolymer, which is biodegradable, biocompatible and non-toxic, has filmogenic properties and is capable of forming matrices for the transport of active substances. The study of chitosan has attracted great interest owing to its ability to form complexes or matrices for the controlled release of active compounds such as micro- and nanoparticles, which, together with the biological properties of chitosan, has allowed a major breakthrough in the pharmaceutical and biomedical industries. Another important field of study is the development of chitosan-based matrices for the controlled release of active compounds in areas such as agriculture and food for the control of viruses, bacteria and fungi, which is one of the least exploited areas and holds much promise for future research.

  16. Responsive polymer-fluorescent carbon nanoparticle hybrid nanogels for optical temperature sensing, near-infrared light-responsive drug release, and tumor cell imaging.

    PubMed

    Wang, Hui; Ke, Fuyou; Mararenko, Anton; Wei, Zengyan; Banerjee, Probal; Zhou, Shuiqin

    2014-07-01

    Fluorescent carbon nanoparticles (FCNPs) have been successfully immobilized into poly(N-isopropylacrylamide-co-acrylamide) [poly(NIPAM-AAm)] nanogels based on one-pot precipitation copolymerization of NIPAM monomers with hydrogen bonded FCNP-AAm complex monomers in water. The resultant poly(NIPAM-AAm)-FCNP hybrid nanogels can combine functions from each building block for fluorescent temperature sensing, cell imaging, and near-infrared (NIR) light responsive drug delivery. The FCNPs in the hybrid nanogels not only emit bright and stable photoluminescence (PL) and exhibit up-conversion PL properties, but also increase the loading capacity of the nanogels for curcumin drug molecules. The reversible thermo-responsive swelling/shrinking transition of the poly(NIPAM-AAm) nanogel can not only modify the physicochemical environment of the FCNPs to manipulate the PL intensity for sensing the environmental temperature change, but also regulate the releasing rate of the loaded anticancer drug. In addition, the FCNPs embedded in the nanogels can convert the NIR light to heat, thus an exogenous NIR irradiation can further accelerate the drug release and enhance the therapeutic efficacy. The hybrid nanogels can overcome cellular barriers to enter the intracellular region and light up the mouse melanoma B16F10 cells upon laser excitation. The demonstrated hybrid nanogels with nontoxic and optically active FCNPs immobilized in responsive polymer nanogels are promising for the development of a new generation of multifunctional materials for biomedical applications. PMID:24881520

  17. Aminated polyethersulfone-silver nanoparticles (AgNPs-APES) composite membranes with controlled silver ion release for antibacterial and water treatment applications.

    PubMed

    Haider, M Salman; Shao, Godlisten N; Imran, S M; Park, Sung Soo; Abbas, Nadir; Tahir, M Suleman; Hussain, Manwar; Bae, Wookeun; Kim, Hee Taik

    2016-05-01

    The present study reports the antibacterial disinfection properties of a series of silver nanoparticle (AgNP) immobilized membranes. Initially, polyethersulfone (PES) was functionalized through the introduction of amino groups to form aminated polyethersulfone (NH2-PES, APES). AgNPs were then coordinately immobilized on the surface of the APES composite membrane to form AgNPs-APES. The properties of the obtained membrane were examined by FT-IR, XPS, XRD, TGA, ICP-OES and SEM-EDAX analyses. These structural characterizations revealed that AgNPs ranging from 5 to 40 nm were immobilized on the surface of the polymer membrane. Antibacterial tests of the samples showed that the AgNPs-APES exhibited higher activity than the AgNPs-PES un-functionalized membrane. Generally, the AgNPs-APES 1 cm × 3 cm strip revealed a four times longer life than the un-functionalized AgNPs polymer membranes. The evaluation of the Ag(+) leaching properties of the obtained samples indicated that approximately 30% of the AgNPs could be retained, even after 12 days of operation. Further analysis indicated that silver ion release can be sustained for approximately 25 days. The present study provides a systematic and novel approach to synthesize water treatment membranes with controlled and improved silver (Ag(+)) release to enhance the lifetime of the membranes.

  18. Luteinizing hormone-releasing hormone targeted poly(methyl vinyl ether maleic acid) nanoparticles for doxorubicin delivery to MCF-7 breast cancer cells.

    PubMed

    Varshosaz, Jaleh; Jahanian-Najafabadi, Ali; Ghazzavi, Jila

    2016-08-01

    The purpose of this study was to design a targeted anti-cancer drug delivery system for breast cancer. Therefore, doxorubicin (DOX) loaded poly(methyl vinyl ether maleic acid) nanoparticles (NPs) were prepared by ionic cross-linking method using Zn(2+) ions. To optimise the effect of DOX/polymer ratio, Zn/polymer ratio, and stirrer rate a full factorial design was used and their effects on particle size, zeta potential, loading efficiency (LE, %), and release efficiency in 72 h (RE72, %) were studied. Targeted NPs were prepared by chemical coating of tiptorelin/polyallylamin conjugate on the surface of NPs by using 1-ethyl-3-(3-dimethylaminopropyl) carboiimid HCl as cross-linking agent. Conjugation efficiency was measured by Bradford assay. Conjugated triptorelin and targeted NPs were studied by Fourier-transform infrared spectroscopy (FTIR). The cytotoxicity of DOX loaded in targeted NPs and non-targeted ones were studied on MCF-7 cells which overexpress luteinizing hormone-releasing hormone (LHRH) receptors and SKOV3 cells as negative LHRH receptors using Thiazolyl blue tetrazolium bromide assay. The best results obtained from NPs prepared by DOX/polymer ratio of 5%, Zn/polymer ratio of 50%, and stirrer rate of 960 rpm. FTIR spectrum confirmed successful conjugation of triptorelin to NPs. The conjugation efficiency was about 70%. The targeted NPs showed significantly less IC50 for MCF-7 cells compared to free DOX and non-targeted NPs. PMID:27463791

  19. Surface modification with dopamine and heparin/poly-L-lysine nanoparticles provides a favorable release behavior for the healing of vascular stent lesions.

    PubMed

    Liu, Tao; Zeng, Zheng; Liu, Yang; Wang, Jian; Maitz, Manfred F; Wang, Yuan; Liu, Shihui; Chen, Junying; Huang, Nan

    2014-06-11

    Surface biofunctional modification of coronary artery stents to prevent thrombosis and restenosis formation, as well as accelerate endothelialization, has become a new hot spot. However, bioactive coatings on implants are not yet sufficiently developed for long-term activity, as they quickly lose efficiency in vivo and finally fail. On the basis of a novel time-ordered concept of biofunctionality for vascular stents, heparin/poly l-lysine nanoparticle (NP) was developed and immobilized on a polydopamine-coated titanium surface, with the aim of regulating and maintaining the intravascular biological response within the normal range after biomaterial implantation. An in vitro dynamic release model was established to mimic the blood flow condition in vivo with three phases: (1) An early phase (1-7 days) with release of predominantly anticoagulant and anti-inflammatory substances and to a minor degree antiproliferative effects against smooth muscle cells (SMCs); (2) this is followed by a phase (7-14 days) of supported endothelial cell (ECs) proliferation and suppressed SMC proliferation with persisting high antithrombogenicity and anti-inflammatory properties of the surface. (3) Finally, a stable stage (14-28 days) with adequate biomolecules on the surface that maintain hemocompatibility and anti inflammation as well as inhibit SMCs proliferation and promote ECs growth. In vivo animal tests further confirmed that the NP-modified surface provides a favorable release behavior to apply a stage-adjusted remedy. We suggested that these observations provide important guidance and potential means for reasonable and suitable platform construction on a stent surface. PMID:24731022

  20. Assessing bio-available silver released from silver nanoparticles embedded in silica layers using the green algae Chlamydomonas reinhardtii as bio-sensors.

    PubMed

    Pugliara, Alessandro; Makasheva, Kremena; Despax, Bernard; Bayle, Maxime; Carles, Robert; Benzo, Patrizio; BenAssayag, Gérard; Pécassou, Béatrice; Sancho, Maria Carmen; Navarro, Enrique; Echegoyen, Yolanda; Bonafos, Caroline

    2016-09-15

    Silver nanoparticles (AgNPs) because of their strong antibacterial activity are widely used in health-care sector and industrial applications. Their huge surface-volume ratio enhances the silver release compared to the bulk material, leading to an increased toxicity for microorganisms sensitive to this element. This work presents an assessment of the toxic effect on algal photosynthesis due to small (size <20nm) AgNPs embedded in silica layers. Two physical approaches were originally used to elaborate the nanocomposite structures: (i) low energy ion beam synthesis and (ii) combined silver sputtering and plasma polymerization. These techniques allow elaboration of a single layer of AgNPs embedded in silica films at defined nanometer distances (from 0 to 7nm) beneath the free surface. The structural and optical properties of the nanostructures were studied by transmission electron microscopy and optical reflectance. The silver release from the nanostructures after 20h of immersion in buffered water was measured by inductively coupled plasma mass spectrometry and ranges between 0.02 and 0.49μM. The short-term toxicity of Ag to photosynthesis of Chlamydomonas reinhardtii was assessed by fluorometry. The obtained results show that embedding AgNPs reduces the interactions with the buffered water free media, protecting the AgNPs from fast oxidation. The release of bio-available silver (impacting on the algal photosynthesis) is controlled by the depth at which AgNPs are located for a given host matrix. This provides a procedure to tailor the toxicity of nanocomposites containing AgNPs. PMID:26953143

  1. Adenosine Triphosphate-Triggered Release of Macromolecular and Nanoparticle Loads from Aptamer/DNA-Cross-Linked Microcapsules.

    PubMed

    Liao, Wei-Ching; Lu, Chun-Hua; Hartmann, Raimo; Wang, Fuan; Sohn, Yang Sung; Parak, Wolfgang J; Willner, Itamar

    2015-09-22

    The synthesis of stimuli-responsive DNA microcapsules acting as carriers for different payloads, and being dissociated through the formation of aptamer-ligand complexes is described. Specifically, stimuli-responsive anti-adenosine triphosphate (ATP) aptamer-cross-linked DNA-stabilized microcapsules loaded with tetramethylrhodamine-modified dextran (TMR-D), CdSe/ZnS quantum dots (QDs), or microperoxidase-11 (MP-11) are presented. In the presence of ATP as trigger, the microcapsules are dissociated through the formation of aptamer-ATP complexes, resulting in the release of the respective loads. Selective unlocking of the capsules is demonstrated, and CTP, GTP, or TTP do not unlock the pores. The ATP-triggered release of MP-11 from the microcapsules enables the MP-11-catalyzed oxidation of Amplex UltraRed by H2O2 to the fluorescent product resorufin. PMID:26266334

  2. Development of novel cationic chitosan-and anionic alginate–coated poly(d,l-lactide-co-glycolide) nanoparticles for controlled release and light protection of resveratrol

    PubMed Central

    Sanna, Vanna; Roggio, Anna Maria; Siliani, Silvia; Piccinini, Massimo; Marceddu, Salvatore; Mariani, Alberto; Sechi, Mario

    2012-01-01

    Background Resveratrol, like other natural polyphenols, is an extremely photosensitive compound with low chemical stability, which limits the therapeutic application of its beneficial effects. The development of innovative formulation strategies, able to overcome physicochemical and pharmacokinetic limitations of this compound, may be achieved via suitable carriers able to associate controlled release and protection. In this context, nanotechnology is proving to be a powerful strategy. In this study, we developed novel cationic chitosan (CS)- and anionic alginate (Alg)-coated poly(d,l-lactide-co-glycolide) nanoparticles (NPs) loaded with the bioactive polyphenolic trans-(E)-resveratrol (RSV) for biomedical applications. Methods NPs were prepared by the nanoprecipitation method and characterized in terms of morphology, size and zeta potential, encapsulation efficiency, Raman spectroscopy, swelling properties, differential scanning calorimetry, and in vitro release studies. The protective effect of the nanosystems under the light-stressed RSV and long-term stability were investigated. Results NPs turned out to be spherical in shape, with size ranging from 135 to about 580 nm, depending on the composition and the amount of polyelectrolytes, while the encapsulation efficiencies increased from 8% of uncoated poly(d,l-lactide-co-glycolide) (PLGA) to 23% and 32% of Alg- and CS-coated PLGA NPs, respectively. All nanocarriers are characterized by a biphasic release pattern, and more effective controlled release rates are obtained for NPs formulated with higher polyelectrolyte concentrations. Stability studies revealed that encapsulation provides significant protection against light-exposure degradation, by reducing the trans–cis photoisomerization reaction. Moreover, the nanosystems are able to prevent the degradation of trans isoform and the leakage of RSV from the carrier for a period of 6 months. Conclusion Our findings indicated that the newly developed CS- and Alg

  3. Mesoporous Silica Nanoparticles Coated by Layer-by-Layer Self-assembly Using Cucurbit[7]uril for in Vitro and in Vivo Anticancer Drug Release

    PubMed Central

    2015-01-01

    Mesoporous silica nanoparticles (MSNs) are promising solid supports for controlled anticancer drug delivery. Herein, we report biocompatible layer-by-layer (LbL) coated MSNs (LbL-MSNs) that are designed and crafted to release encapsulated anticancer drugs, e.g., doxorubicin hydrochloride (DOX), by changing the pH or by adding competitive agents. The LbL coating process comprises bis-aminated poly(glycerol methacrylate)s (BA-PGOHMAs) and cucurbit[7]uril (CB[7]), where CB[7] serves as a molecular bridge holding two different bis-aminated polymeric layers together by means of host–guest interactions. This integrated nanosystem is tuned to respond under specific acidic conditions or by adding adamantaneamine hydrochloride (AH), attributed to the competitive binding of hydronium ions or AH to CB[7] with BA-PGOHMAs. These LbL-MSN hybrids possess excellent biostability, negligible premature drug leakage at pH 7.4, and exceptional stimuli-responsive drug release performance. The pore sizes of the MSNs and bis-aminated compounds (different carbon numbers) of BA-PGOHMAs have been optimized to provide effective integrated nanosystems for the loading and release of DOX. Significantly, the operating pH for the controlled release of DOX matches the acidifying endosomal compartments of HeLa cancer cells, suggesting that these hybrid nanosystems are good candidates for autonomous anticancer drug nanocarriers actuated by intracellular pH changes without any invasive external stimuli. The successful cellular uptake and release of cargo, e.g., propidium iodide (PI), in human breast cancer cell line MDA-231 from PI-loaded LbL-MSNs have been confirmed by confocal laser scanning microscopy (CLSM), while the cytotoxicities of DOX-loaded LbL-MSNs have been quantified by the Cell Counting Kit-8 (CCK-8) viability assay against HeLa cell lines and fibroblast L929 cell lines. The uptake of DOX-loaded LbL-MSNs by macrophages can be efficiently reduced by adding biocompatible hydrophilic poly

  4. Toxic responses in rat embryonic cells to silver nanoparticles and released silver ions as analyzed via gene expression profiles and transmission electron microscopy.

    PubMed

    Xu, Liming; Shi, Chang; Shao, Anliang; Li, Xuefei; Cheng, Xiang; Ding, Rigao; Wu, Gang; Chou, Laisheng Lee

    2015-05-01

    After exposing rat embryonic cells to 20 μg/mL of silver nanoparticle (NP) suspension and their released ions for different time periods, silver nanoparticles were found in cellular nuclei, mitochondria, cytoplasm and lysosomes by transmission electron microscopy (TEM). We also observed mitochondrial destruction, distension of endoplasmic reticulum and apoptotic bodies. Global gene expression analysis showed a total of 279 genes that were up-regulated and 389 genes that were down-regulated in the silver-NP suspension exposure group, while 3 genes were up-regulated and 41 genes were down-regulated in the silver ion exposure group. Further, the GO pathway analysis suggested that these differentially expressed genes are involved in several biological processes, such as energy metabolism, oxygen transport, enzyme activities, molecular binding, etc. It is possible that inhibition of oxygen transport is mediated by the significant down-regulation of genes of the globin family, which might play an important role in silver ion-induced toxicity. KEGG pathway analysis showed that there were 23 signal pathways that were affected in the cells after exposure to silver-NP suspension, but not silver ion alone. The most significant change concerned inflammatory signal pathways, which were only found in silver-NP suspension exposed cells, indicating that inflammatory response might play an important role in the mechanism(s) of silver-NP-induced toxicity. The significant up-regulation of matrix metalloproteinases 3 and 9 suggests that silver NPs could induce extracellular matrix degradation via an inflammatory signaling pathway. The significant up-regulation of secretory leukocyte peptidase inhibitor and serine protease inhibitor 2c was considered to be an embryonic cellular defense mechanism in response to silver-NP-induced inflammation.

  5. WE-G-BRE-09: Targeted Radiotherapy Enhancement During Accelerated Partial Breast Irradiation (ABPI) Using Controlled Release of Gold Nanoparticles (GNPs)

    SciTech Connect

    Cifter, G; Ngwa, W; Chin, J; Cifter, F; Sajo, E; Sinha, N; Bellon, J

    2014-06-15

    Purpose: Several studies have demonstrated low rates of local recurrence with brachytherapy-based accelerated partial breast irradiation (APBI). However, long-term outcomes on toxicity (e.g. telangiectasia), and cosmesis remain a major concern. The purpose of this study is to investigate the dosimetric feasibility of using targeted non-toxic radiosensitizing gold nanoparticles (GNPs) for localized dose enhancement to the planning target volume (PTV) during APBI while reducing dose to normal tissue. Methods: Two approaches for administering the GNPs were considered. In one approach, GNPs are assumed to be incorporated in a micrometer-thick polymer film on the surface of routinely used mammosite balloon applicators, for sustained controlled in-situ release, and subsequent treatment using 50-kVp Xoft devices. In case two, GNPs are administered directly into the lumpectomy cavity e.g. via injection or using fiducials coated with the GNP-loaded polymer film. Recent studies have validated the use of fiducials for reducing the PTV margin during APBI with 6 MV beams. An experimentally determined diffusion coefficient was used to determine space-time customizable distribution of GNPs for feasible in-vivo concentrations of 43 mg/g. An analytic calculational approach from previously published work was employed to estimate the dose enhancement due to GNPs (2 and 10 nm) as a function of distance up to 1 cm from lumpectomy cavity. Results: Dose enhancement due to GNP was found to be about 130% for 50-kVp x-rays, and 110% for 6-MV external beam radiotherapy, 1 cm away from the lumpectomy cavity wall. Higher customizable dose enhancement could be achieved at other distances as a function of nanoparticle size. Conclusion: Our preliminary results suggest that significant dose enhancement can be achieved to residual tumor cells targeted with GNPs during APBI with electronic brachytherapy or external beam therapy. The findings provide a useful basis for developing nanoparticle

  6. Mitomycin C-soybean phosphatidylcholine complex-loaded self-assembled PEG-lipid-PLA hybrid nanoparticles for targeted drug delivery and dual-controlled drug release.

    PubMed

    Li, Yang; Wu, Hongjie; Yang, Xiangrui; Jia, Mengmeng; Li, Yanxiu; Huang, Yu; Lin, Jinyan; Wu, Shichao; Hou, Zhenqing

    2014-08-01

    Most present drug-phospholipid delivery systems were based on a water-insoluble drug-phospholipid complex but rarely water-soluble drug-phospholipid complex. Mitomycin C (MMC) is a water-soluble anticancer drug extensively used in first-line chemotherapy but is limited by its poor aqueous stability in vitro, rapid elimination from the body, and lack of target specificity. In this article, we report the MMC-soybean phosphatidylcholine complex-loaded PEG-lipid-PLA hybrid nanoparticles (NPs) with Folate (FA) functionalization (FA-PEG-PE-PLA NPs@MMC-SPC) for targeted drug delivery and dual-controlled drug release. FA-PEG-PE-PLA NPs@MMC-SPC comprise a hydrophobic core (PLA) loaded with MMC-SPC, an amphiphilic lipid interface layer (PE), a hydrophilic shell (PEG), and a targeting ligand (FA) on the surface, with a spherical shape, a nanoscaled particle size, and high drug encapsulation efficiency of almost 95%. The advantage of the new drug delivery systems is the early phase controlled drug release by the drug-phospholipid complex and the late-phase controlled drug release by the pH-sensitive polymer-lipid hybrid NPs. In vitro cytotoxicity and hemolysis assays demonstrated that the drug carriers were cytocompatible and hemocompatible. The pharmacokinetics study in rats showed that FA-PEG-PE-PLA NPs@MMC-SPC significantly prolonged the blood circulation time compared to that of the free MMC. More importantly, FA-PEG-PE-PLA NPs@MMC-SPC presented the enhanced cell uptake/cytotoxicity in vitro and superior tumor accumulation/therapeutic efficacy in vivo while reducing the systemic toxicity. A significant accumulation of MMC in the nuclei as the site of MMC action achieved in FA-PEG-PE-PLA NPs@MMC-SPC made them ideal for MMC drug delivery. This study may provide an effective strategy for the design and development of the water-soluble drug-phospholipid complex-based targeted drug delivery and sustained/controlled drug release.

  7. Synthesis of doxorubicin-PLGA loaded chitosan stabilized (Mn, Zn)Fe2O4 nanoparticles: Biological activity and pH-responsive drug release.

    PubMed

    Montha, Wararat; Maneeprakorn, Weerakanya; Buatong, Nattha; Tang, I-Ming; Pon-On, Weeraphat

    2016-02-01

    We have synthesized Mn1-xZnxFe2O4 ((Mn, Zn) ferrite) magnetic nanoparticles (MNPs) having radius of 25nm to act as platforms for delivering drugs. The Mn0.9Zn0.1Fe2O4 MNPs exhibit superparamagnetic behavior with large saturation magnetization (MS). They were encapsulated in polymer so that they can be developed into PLGA-coated chitosan stabilized (Mn, Zn) MNPs, i.e., DOX-PLGA@CS@Mn0.9Zn0.1Fe2O4 which can serve as an effective carrier of the anti-cancer drug doxorubicin (DOX) whose release would be controlled by the pH in the environment surrounding the cancer tumor. The structure of the as-prepared particles is of a magnetic core-encapsulated by polymer shell layer of around 50nm thick. At a pH of 4.0, the DOX release within the first 5h is fast (around 57%). It becomes slower (around 46% over the next 25h) when the pH is increased to 7.4. The DOX-PLGA@CS@Mn0.9Zn0.1Fe2O4 (for concentrations lower than 125μgmL(-1)) shows lower toxicity against HeLa cells using DOX only. When the DOX-PLGA@CS@Mn0.9Zn0.1Fe2O4 is increased to 250μgmL(-1), the DOX-PLGA@CS@Mn0.9Zn0.1Fe2O4 shows greater anti-cancer activity and has satisfactory therapeutic effect. The slow sustained release of the DOX by the drug loaded particles when they are in the physiological pH environment (7.4) of normal tissues and mild toxicity of DOX against cancer cell at low concentration point to the DOX loaded PLGA@CS@Mn0.9Zn0.1Fe2O4 being safely used for treating cancer. The higher dosage of DOX needed to kill the cancer cells will be released when the synthesized carriers are subject to the pH stimuli surrounding these cells.

  8. Synthesis of doxorubicin-PLGA loaded chitosan stabilized (Mn, Zn)Fe2O4 nanoparticles: Biological activity and pH-responsive drug release.

    PubMed

    Montha, Wararat; Maneeprakorn, Weerakanya; Buatong, Nattha; Tang, I-Ming; Pon-On, Weeraphat

    2016-02-01

    We have synthesized Mn1-xZnxFe2O4 ((Mn, Zn) ferrite) magnetic nanoparticles (MNPs) having radius of 25nm to act as platforms for delivering drugs. The Mn0.9Zn0.1Fe2O4 MNPs exhibit superparamagnetic behavior with large saturation magnetization (MS). They were encapsulated in polymer so that they can be developed into PLGA-coated chitosan stabilized (Mn, Zn) MNPs, i.e., DOX-PLGA@CS@Mn0.9Zn0.1Fe2O4 which can serve as an effective carrier of the anti-cancer drug doxorubicin (DOX) whose release would be controlled by the pH in the environment surrounding the cancer tumor. The structure of the as-prepared particles is of a magnetic core-encapsulated by polymer shell layer of around 50nm thick. At a pH of 4.0, the DOX release within the first 5h is fast (around 57%). It becomes slower (around 46% over the next 25h) when the pH is increased to 7.4. The DOX-PLGA@CS@Mn0.9Zn0.1Fe2O4 (for concentrations lower than 125μgmL(-1)) shows lower toxicity against HeLa cells using DOX only. When the DOX-PLGA@CS@Mn0.9Zn0.1Fe2O4 is increased to 250μgmL(-1), the DOX-PLGA@CS@Mn0.9Zn0.1Fe2O4 shows greater anti-cancer activity and has satisfactory therapeutic effect. The slow sustained release of the DOX by the drug loaded particles when they are in the physiological pH environment (7.4) of normal tissues and mild toxicity of DOX against cancer cell at low concentration point to the DOX loaded PLGA@CS@Mn0.9Zn0.1Fe2O4 being safely used for treating cancer. The higher dosage of DOX needed to kill the cancer cells will be released when the synthesized carriers are subject to the pH stimuli surrounding these cells. PMID:26652369

  9. Responsive polymer-fluorescent carbon nanoparticle hybrid nanogels for optical temperature sensing, near-infrared light-responsive drug release, and tumor cell imaging

    NASA Astrophysics Data System (ADS)

    Wang, Hui; Ke, Fuyou; Mararenko, Anton; Wei, Zengyan; Banerjee, Probal; Zhou, Shuiqin

    2014-06-01

    Fluorescent carbon nanoparticles (FCNPs) have been successfully immobilized into poly(N-isopropylacrylamide-co-acrylamide) [poly(NIPAM-AAm)] nanogels based on one-pot precipitation copolymerization of NIPAM monomers with hydrogen bonded FCNP-AAm complex monomers in water. The resultant poly(NIPAM-AAm)-FCNP hybrid nanogels can combine functions from each building block for fluorescent temperature sensing, cell imaging, and near-infrared (NIR) light responsive drug delivery. The FCNPs in the hybrid nanogels not only emit bright and stable photoluminescence (PL) and exhibit up-conversion PL properties, but also increase the loading capacity of the nanogels for curcumin drug molecules. The reversible thermo-responsive swelling/shrinking transition of the poly(NIPAM-AAm) nanogel can not only modify the physicochemical environment of the FCNPs to manipulate the PL intensity for sensing the environmental temperature change, but also regulate the releasing rate of the loaded anticancer drug. In addition, the FCNPs embedded in the nanogels can convert the NIR light to heat, thus an exogenous NIR irradiation can further accelerate the drug release and enhance the therapeutic efficacy. The hybrid nanogels can overcome cellular barriers to enter the intracellular region and light up the mouse melanoma B16F10 cells upon laser excitation. The demonstrated hybrid nanogels with nontoxic and optically active FCNPs immobilized in responsive polymer nanogels are promising for the development of a new generation of multifunctional materials for biomedical applications.Fluorescent carbon nanoparticles (FCNPs) have been successfully immobilized into poly(N-isopropylacrylamide-co-acrylamide) [poly(NIPAM-AAm)] nanogels based on one-pot precipitation copolymerization of NIPAM monomers with hydrogen bonded FCNP-AAm complex monomers in water. The resultant poly(NIPAM-AAm)-FCNP hybrid nanogels can combine functions from each building block for fluorescent temperature sensing, cell imaging

  10. UV and dark-triggered repetitive release and encapsulation of benzophenone-3 from biocompatible ZnO nanoparticles potential for skin protection

    NASA Astrophysics Data System (ADS)

    Huang, Xiao; Wang, Xiaoying; Wang, Sichun; Yang, Jiawen; Zhong, Li; Pan, Jun

    2013-05-01

    The present study reports a UV and dark-triggered highly intelligent drug delivery system for skin protection. ZnO nanoparticles (NPs), a UV filter, were synthesized and characterized to be the carrier for benzophenone-3 (Bp-3), a UV-absorption medicine, by varying the molar ratio of ZnO NPs to Bp-3 ranging from 300 : 1 to 20 : 1. The drug release under three cycles of UV and dark stimulation (each for two hours) and its cytotoxicity to human keratinocyte cells and skin fibroblasts were investigated. SEM studies showed the diameter of ZnO was around 30 to 40 nm, which assembled into loose and large NPs ranging from 500 to 1400 nm. Contact angle tests showed ZnO NPs switched to a more hydrophilic and back to a more hydrophobic state under two hours of UV and dark exposure. The optimized encapsulation efficiency and loading capacity of Bp-3 were 53.68 +/- 0.13% and 133.61 +/- 0.20% when the molar ratio of ZnO NPs to Bp-3 was 150 : 1 and 80 : 1. The Bp-3 was almost completely released from ZnO NPs under 2 hours of UV radiation and was mostly encapsulated in after 2 hours of dark stay in three cycles of UV and dark exposure. The Bp-3 loaded ZnO NPs showed low cytotoxicity to human keratinocyte cells and human skin fibroblasts. Overall, a UV and dark-triggered repetitively on-demand drug delivery system biocompatible to skin cells and potential for skin protection from UV radiation was developed.

  11. Dry powders based on PLGA nanoparticles for pulmonary delivery of antibiotics: modulation of encapsulation efficiency, release rate and lung deposition pattern by hydrophilic polymers.

    PubMed

    Ungaro, Francesca; d'Angelo, Ivana; Coletta, Ciro; d'Emmanuele di Villa Bianca, Roberta; Sorrentino, Raffaella; Perfetto, Brunella; Tufano, Maria Antonietta; Miro, Agnese; La Rotonda, Maria Immacolata; Quaglia, Fabiana

    2012-01-10

    Although few experimental studies have been handled so far to exploit the potential of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) in the production of dry powders for antibiotic inhalation, there has been no comprehensive study on the role played by NP composition. In this work, we try to shed light on this aspect by designing and developing a pulmonary delivery system for antibiotics, such as tobramycin (Tb), based on PLGA NPs embedded in an inert microcarrier made of lactose, referred to as nano-embedded micro-particles (NEM). At nanosize level, helper hydrophilic polymers were used to impart the desired surface, bulk and release properties to PLGA NPs prepared by a modified emulsion-solvent diffusion technique. Results showed that poly(vinyl alcohol) (PVA) and chitosan (CS) are essential to optimise the size and modulate the surface properties of Tb-loaded PLGA NPs, whereas the use of alginate (Alg) allows efficient Tb entrapment within NPs and its release up to one month. Optimized formulations display good in vitro antimicrobial activity against P. aeruginosa planktonic cells. Furthermore, spray-drying of the NPs with lactose yielded NEM with peculiar but promising flow and aerosolization properties, while preserving the peculiar NP features. Nonetheless, in vivo biodistribution studies showed that PVA-modified Alg/PLGA NPs reached the deep lung, while CS-modified NPs were found in great amounts in the upper airways, lining lung epithelial surfaces. In conclusion, PLGA NP composition appears to play a crucial role in determining not only the technological features of NPs but, once processed in the form of NEM, also their in vitro/in vivo deposition pattern.

  12. UV and dark-triggered repetitive release and encapsulation of benzophenone-3 from biocompatible ZnO nanoparticles potential for skin protection.

    PubMed

    Huang, Xiao; Wang, Xiaoying; Wang, Sichun; Yang, Jiawen; Zhong, Li; Pan, Jun

    2013-06-21

    The present study reports a UV and dark-triggered highly intelligent drug delivery system for skin protection. ZnO nanoparticles (NPs), a UV filter, were synthesized and characterized to be the carrier for benzophenone-3 (Bp-3), a UV-absorption medicine, by varying the molar ratio of ZnO NPs to Bp-3 ranging from 300 : 1 to 20 : 1. The drug release under three cycles of UV and dark stimulation (each for two hours) and its cytotoxicity to human keratinocyte cells and skin fibroblasts were investigated. SEM studies showed the diameter of ZnO was around 30 to 40 nm, which assembled into loose and large NPs ranging from 500 to 1400 nm. Contact angle tests showed ZnO NPs switched to a more hydrophilic and back to a more hydrophobic state under two hours of UV and dark exposure. The optimized encapsulation efficiency and loading capacity of Bp-3 were 53.68 ± 0.13% and 133.61 ± 0.20% when the molar ratio of ZnO NPs to Bp-3 was 150 : 1 and 80 : 1. The Bp-3 was almost completely released from ZnO NPs under 2 hours of UV radiation and was mostly encapsulated in after 2 hours of dark stay in three cycles of UV and dark exposure. The Bp-3 loaded ZnO NPs showed low cytotoxicity to human keratinocyte cells and human skin fibroblasts. Overall, a UV and dark-triggered repetitively on-demand drug delivery system biocompatible to skin cells and potential for skin protection from UV radiation was developed. PMID:23680782

  13. Conjugated polymer and drug co-encapsulated nanoparticles for Chemo- and Photo-thermal Combination Therapy with two-photon regulated fast drug release

    NASA Astrophysics Data System (ADS)

    Yuan, Youyong; Wang, Zuyong; Cai, Pingqiang; Liu, Jie; Liao, Lun-De; Hong, Minghui; Chen, Xiaodong; Thakor, Nitish; Liu, Bin

    2015-02-01

    The spatial-temporal synchronization of photothermal therapy and chemotherapy is highly desirable for an efficient cancer treatment with synergistic effect. Herein, we developed a chemotherapeutic drug doxorubicin (DOX) and photothermal conjugated polymer (CP) co-loaded nanoplatform using a near-infrared (NIR) laser responsive amphiphilic brush copolymer as the encapsulation matrix. The obtained nanoparticles (NPs) exhibit good monodispersity and excellent stability, which can efficiently convert laser energy into thermal energy for photothermal therapy. Moreover, the hydrophobic polymer matrix bearing a number of 2-diazo-1,2-naphthoquinones (DNQ) moieties could be transformed to a hydrophilic one upon NIR two-photon laser irradiation, which leads to fast drug release. Furthermore, the surface modification of the NPs with cyclic arginine-glycine-aspartic acid (cRGD) tripeptide significantly enhances the accumulation of the NPs within integrin αvβ3 overexpressed cancer cells. The half-maximal inhibitory concentration (IC50) of the combination therapy is 13.7 μg mL-1, while the IC50 for chemotherapy and photothermal therapy alone is 147.8 μg mL-1 and 36.2 μg mL-1, respectively. The combination index (C.I.) is 0.48 (<1), which indicates the synergistic effect for chemotherapy and PTT. These findings provide an excellent NIR laser regulated nanoplatform for combined cancer treatment with synergistic effect due to the synchronous chemo- and photo-thermal therapy.

  14. Effect of polymer architecture on curcumin encapsulation and release from PEGylated polymer nanoparticles: Toward a drug delivery nano-platform to the CNS.

    PubMed

    Rabanel, Jean-Michel; Faivre, Jimmy; Paka, Ghislain Djiokeng; Ramassamy, Charles; Hildgen, Patrice; Banquy, Xavier

    2015-10-01

    We developed a nanoparticles (NPs) library from poly(ethylene glycol)-poly lactic acid comb-like polymers with variable amount of PEG. Curcumin was encapsulated in the NPs with a view to develop a delivery platform to treat diseases involving oxidative stress affecting the CNS. We observed a sharp decrease in size between 15 and 20% w/w of PEG which corresponds to a transition from a large solid particle structure to a "micelle-like" or "polymer nano-aggregate" structure. Drug loading, loading efficacy and release kinetics were determined. The diffusion coefficients of curcumin in NPs were determined using a mathematical modeling. The higher diffusion was observed for solid particles compared to "polymer nano-aggregate" particles. NPs did not present any significant toxicity when tested in vitro on a neuronal cell line. Moreover, the ability of NPs carrying curcumin to prevent oxidative stress was evidenced and linked to polymer architecture and NPs organization. Our study showed the intimate relationship between the polymer architecture and the biophysical properties of the resulting NPs and sheds light on new approaches to design efficient NP-based drug carriers.

  15. Anti-leukemia activity of PVP-coated silver nanoparticles via generation of reactive oxygen species and release of silver ions.

    PubMed

    Guo, Dawei; Zhu, Lingying; Huang, Zhihai; Zhou, Haixia; Ge, Yue; Ma, Wenjuan; Wu, Jie; Zhang, Xiuyan; Zhou, Xuefeng; Zhang, Yu; Zhao, Yun; Gu, Ning

    2013-10-01

    Silver nanoparticles (AgNPs) have anti-cancer effect. However, whether and how these particles could inhibit the growth of acute myeloid leukemia (AML) cells is unclear. In the present study, we prepared AgNPs with various sizes and investigated their cytotoxic effect on AML cells. We found that AgNPs could inhibit the viability of AML cells including the isolates from AML patients. AgNPs caused the production of reactive oxygen species (ROS), losses of mitochondrial membrane potential (MMP), DNA damage and apoptosis. Both vitamin C (Vit C) and N-acetyl-L-cysteine (NAC) could completely reverse the generation of ROS upon AgNPs, however only NAC but not Vit C could protect the cells from losses of MMP, DNA damage and apoptosis thoroughly. Similar results were obtained when cells were treated with silver ions alone. As NAC was not only an antioxidant to scavenge ROS but also a silver ion chelator, these data supported the model that both generation of ROS and release of silver ions played critical roles in the AgNPs-induced cytotoxic effect against AML cells. Taken together, this work elucidated the cytotoxic effect of AgNPs on AML cells and their underlying mechanism and might have significant impact on AML treatment.

  16. Nrf2 protects the lung against inflammation induced by titanium dioxide nanoparticles: A positive regulator role of Nrf2 on cytokine release.

    PubMed

    Delgado-Buenrostro, Norma L; Medina-Reyes, Estefany I; Lastres-Becker, Isabel; Freyre-Fonseca, Verónica; Ji, Zhaoxia; Hernández-Pando, Rogelio; Marquina, Brenda; Pedraza-Chaverri, José; Espada, Sandra; Cuadrado, Antonio; Chirino, Yolanda I

    2015-07-01

    Titanium dioxide nanoparticles (TiO2 NPs) have been classified as possibly carcinogenic to humans and they are an important nanomaterial widely used in pharmaceutical and paint industries. Inhalation is one of the most important routes of exposure in occupational settings. Several experimental models have shown that oxidative stress and inflammation are key mediators of cell damage. In this regard, Nrf2 modulates cytoprotection against oxidative stress and inflammation, however, its role in inflammation induced by TiO2 NPs exposure has been less investigated. The aim of this work was to investigate the role of Nrf2 in the cytokines produced after 4 weeks of TiO2 NPs exposure (5 mg/kg/2 days/week) using wild-type and Nrf2 knockout C57bl6 mice. Results showed that Nrf2 protects against inflammation and oxidative damage induced by TiO2 NPs exposure, however, Nrf2 is a positive mediator in the expression of IFN-γ, TNF-α, and TGF-β in bronchial epithelium and alveolar space after 4 weeks of exposure. These results suggest that Nrf2 has a central role in up-regulation of cytokines released during inflammation induced by TiO2 NPs and those cytokines are needed to cope with histological alterations in lung tissue.

  17. Poly(D, L-lactide-co-glycolide) nanoparticles as delivery agents for photodynamic therapy: enhancing singlet oxygen release and photototoxicity by surface PEG coating

    NASA Astrophysics Data System (ADS)

    Boix-Garriga, Ester; Acedo, Pilar; Casadó, Ana; Villanueva, Angeles; Stockert, Juan Carlos; Cañete, Magdalena; Mora, Margarita; Lluïsa Sagristá, Maria; Nonell, Santi

    2015-09-01

    Poly(D, L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) are being considered as nanodelivery systems for photodynamic therapy. The physico-chemical and biological aspects of their use remain largely unknown. Herein we report the results of a study of PLGA NPs for the delivery of the model hydrophobic photosensitizer ZnTPP to HeLa cells. ZnTPP was encapsulated in PLGA with high efficiency and the NPs showed negative zeta potentials and diameters close to 110 nm. Poly(ethylene glycol) (PEG) coating, introduced to prevent opsonization and clearance by macrophages, decreased the size and zeta potential of the NPs by roughly a factor of two and improved their stability in the presence of serum proteins. Photophysical studies revealed two and three populations of ZnTPP and singlet oxygen in uncoated and PEGylated NPs, respectively. Singlet oxygen is confined within the NPs in bare PLGA while it is more easily released into the external medium after PEG coating, which contributes to a higher photocytotoxicity towards HeLa cells in vitro. PLGA NPs are internalized by endocytosis, deliver their cargo to lysosomes and induce cell death by apoptosis upon exposure to light. In conclusion, PLGA NPs coated with PEG show high potential as delivery systems for photodynamic applications.

  18. Application of Box-Behnken design for preparation of levofloxacin-loaded stearic acid solid lipid nanoparticles for ocular delivery: Optimization, in vitro release, ocular tolerance, and antibacterial activity.

    PubMed

    Baig, Mirza Salman; Ahad, Abdul; Aslam, Mohammed; Imam, Syed Sarim; Aqil, Mohd; Ali, Asgar

    2016-04-01

    The aim of the present study was to develop and optimize levofloxacin loaded solid lipid nanoparticles for the treatment of conjunctivitis. Box-Behnken experimental design was applied for optimization of solid lipid nanoparticles. The independent variables were stearic acid as lipid (X1), Tween 80 as surfactant (X2) and sodium deoxycholate as co-surfactant (X3) while particle size (Y1) and entrapment efficiency (Y2) were the dependent variables. Further in vitro release and antibacterial activity in vitro were also performed. The optimized formulation of levofloxacin provides particle size of 237.82 nm and showed 78.71% entrapment efficiency and achieved flux 0.2,493 μg/cm(2)/h across excised goat cornea. In vitro release study showed prolonged drug release from the optimized formulation following Korsmeyer-Peppas model. Antimicrobial study revealed that the developed formulation possesses antibacterial activity against Staphylococcus aureus, and Escherichia coli equivalent to marketed eye drops. HET-CAM test demonstrated that optimized formulation was found to be non-irritant and safe for topical ophthalmic use. Our results concluded that solid lipid nanoparticles are an efficient carrier for ocular delivery of levofloxacin and other drugs.

  19. Effects of fat, protein, and carbohydrate and protein load on appetite, plasma cholecystokinin, peptide YY, and ghrelin, and energy intake in lean and obese men.

    PubMed

    Brennan, Ixchel M; Luscombe-Marsh, Natalie D; Seimon, Radhika V; Otto, Bärbel; Horowitz, Michael; Wishart, Judith M; Feinle-Bisset, Christine

    2012-07-01

    While protein is regarded as the most satiating macronutrient, many studies have employed test meals that had very high and unsustainable protein contents. Furthermore, the comparative responses between lean and obese subjects and the relationships between energy intake suppression and gut hormone release remain unclear. We evaluated the acute effects of meals with modest variations in 1) fat, protein, and carbohydrate content and 2) protein load on gastrointestinal hormones, appetite, and subsequent energy intake in lean and obese subjects. Sixteen lean and sixteen obese men were studied on four occasions. Following a standardized breakfast, they received for lunch: 1) high-fat (HF), 2) high-protein (HP), 3) high-carbohydrate/low-protein (HC/LP), or 4) adequate-protein (AP) isocaloric test meals. Hunger, fullness, and gut hormones were measured throughout, and at t = 180 min energy intake at a buffet meal was quantified. In lean subjects, hunger was less and fullness greater following HF, HP, and AP compared with HC/LP meals, and energy intake was less following HF and HP compared with HC meals (P < 0.05). In the obese subjects, hunger was less following HP compared with HF, HC/LP, and AP meals, and energy intake was less following HP and AP compared with HF and HC meals (P < 0.05). There were no major differences in hormone responses to the meals among subject groups, but the CCK and ghrelin responses to HP and AP were sustained in both groups. In conclusion, HP meals suppress energy intake in lean and obese subjects, an effect potentially mediated by CCK and ghrelin, while obese individuals appear to be less sensitive to the satiating effects of fat.

  20. Transport, retention, and long-term release behavior of ZnO nanoparticle aggregates in saturated quartz sand: Role of solution pH and biofilm coating.

    PubMed

    Han, Yosep; Hwang, Gukhwa; Kim, Donghyun; Bradford, Scott A; Lee, Byoungcheun; Eom, Igchun; Kim, Pil Je; Choi, Siyoung Q; Kim, Hyunjung

    2016-03-01

    The transport, retention, and long-term release of zinc oxide nanoparticle aggregates (denoted below as ZnO-NPs) were investigated in saturated, bare and biofilm (Pseudomonas putida) coated sand packed columns. Almost complete retention of ZnO-NPs occurred in bare and biofilm coated sand when the influent solution pH was 9 and the ionic strength (IS) was 0.1 or 10 mM NaCl, and the retention profiles were always hyper-exponential. Increasing the solution IS and biofilm coating produced enhanced retention of ZnO-NPs near the column inlet. The enhanced NPs retention at high IS was attributed to more favorable NP-silica and NP-NP interactions; this was consistent with the interaction energy calculations. Meanwhile, the greater NPs retention in the presence of biofilm was attributed to larger roughness heights which alter the mass transfer rate, the interaction energy profile, and lever arms associated with the torque balance; e.g., scanning electron and atomic force microscopy was used to determine roughness heights of 33.4 nm and 97.8 nm for bare sand and biofilm-coated sand, respectively. Interactions between NPs and extracellular polymeric substances may have also contributed to enhanced NP retention in biofilm-coated sand at low IS. The long-term release of retained ZnO-NPs was subsequently investigated by continuously injecting NP-free solution at pH 6, 9, or 10 and keeping the IS constant at 10 mM. The amount and rate of retained ZnO-NP removal was strongly dependent on the solution pH. Specifically, almost complete removal of retained ZnO-NPs was observed after 627 pore volumes when the solution pH was 6, whereas much less Zn was recovered when the eluting solution pH was buffered to pH = 9 and especially 10. This long-term removal was attributed to pH-dependent dissolution of retained ZnO-NPs because: (i) the solubility of ZnO-NPs increases with decreasing pH; and (ii) ZnO-NPs were not detected in the effluent. The presence of biofilm also decreased the

  1. Transport, retention, and long-term release behavior of ZnO nanoparticle aggregates in saturated quartz sand: Role of solution pH and biofilm coating.

    PubMed

    Han, Yosep; Hwang, Gukhwa; Kim, Donghyun; Bradford, Scott A; Lee, Byoungcheun; Eom, Igchun; Kim, Pil Je; Choi, Siyoung Q; Kim, Hyunjung

    2016-03-01

    The transport, retention, and long-term release of zinc oxide nanoparticle aggregates (denoted below as ZnO-NPs) were investigated in saturated, bare and biofilm (Pseudomonas putida) coated sand packed columns. Almost complete retention of ZnO-NPs occurred in bare and biofilm coated sand when the influent solution pH was 9 and the ionic strength (IS) was 0.1 or 10 mM NaCl, and the retention profiles were always hyper-exponential. Increasing the solution IS and biofilm coating produced enhanced retention of ZnO-NPs near the column inlet. The enhanced NPs retention at high IS was attributed to more favorable NP-silica and NP-NP interactions; this was consistent with the interaction energy calculations. Meanwhile, the greater NPs retention in the presence of biofilm was attributed to larger roughness heights which alter the mass transfer rate, the interaction energy profile, and lever arms associated with the torque balance; e.g., scanning electron and atomic force microscopy was used to determine roughness heights of 33.4 nm and 97.8 nm for bare sand and biofilm-coated sand, respectively. Interactions between NPs and extracellular polymeric substances may have also contributed to enhanced NP retention in biofilm-coated sand at low IS. The long-term release of retained ZnO-NPs was subsequently investigated by continuously injecting NP-free solution at pH 6, 9, or 10 and keeping the IS constant at 10 mM. The amount and rate of retained ZnO-NP removal was strongly dependent on the solution pH. Specifically, almost complete removal of retained ZnO-NPs was observed after 627 pore volumes when the solution pH was 6, whereas much less Zn was recovered when the eluting solution pH was buffered to pH = 9 and especially 10. This long-term removal was attributed to pH-dependent dissolution of retained ZnO-NPs because: (i) the solubility of ZnO-NPs increases with decreasing pH; and (ii) ZnO-NPs were not detected in the effluent. The presence of biofilm also decreased the

  2. In situ remediation-released zero-valent iron nanoparticles impair soil ecosystems health: A C. elegans biomarker-based risk assessment.

    PubMed

    Yang, Ying-Fei; Cheng, Yi-Hsien; Liao, Chung-Min

    2016-11-01

    There is considerable concern over the potential ecotoxicity to soil ecosystems posed by zero-valent iron nanoparticles (Fe(0) NPs) released from in situ environmental remediation. However, a lack of quantitative risk assessment has hampered the development of appropriate testing methods used in environmental applications. Here we present a novel, empirical approach to assess Fe(0) NPs-associated soil ecosystems health risk using the nematode Caenorhabditis elegans as a model organism. A Hill-based dose-response model describing the concentration-fertility inhibition relationships was constructed. A Weibull model was used to estimate thresholds as a guideline to protect C. elegans from infertility when exposed to waterborne or foodborne Fe(0) NPs. Finally, the risk metrics, exceedance risk (ER) and risk quotient (RQ) of Fe(0) NPs in various depths and distances from remediation sites can then be predicted. We showed that under 50% risk probability (ER=0.5), upper soil layer had the highest infertility risk (95% confidence interval: 13.18-57.40%). The margins of safety and acceptable criteria for soil ecosystems health for using Fe(0) NPs in field scale applications were also recommended. Results showed that RQs are larger than 1 in all soil layers when setting a stricter threshold of ∼1.02mgL(-1) of Fe(0) NPs. This C. elegans biomarker-based risk model affords new insights into the links between widespread use of Fe(0) NPs and environmental risk assessment and offers potential environmental implications of metal-based NPs for in situ remediation.

  3. Controlled release of B-carotene in B-lactoglobulin-dextran conjugates nanoparticles in vitro digestion and the transport with Caco-2 monolayers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chitosan–tripolyphosphate nanoparticles have been extensively studied during the last decade because of their numerous applications. In this study, we describe conditions to optimize chitosan nanoparticles as potential nano-fillers in edible films. The ionic cross-linking between the cationic amino ...

  4. Amifostine-conjugated pH-sensitive calcium phosphate-covered magnetic-amphiphilic gelatin nanoparticles for controlled intracellular dual drug release for dual-targeting in HER-2-overexpressing breast cancer.

    PubMed

    Li, Wei-Ming; Chiang, Chih-Sheng; Huang, Wei-Chen; Su, Chia-Wei; Chiang, Min-Yu; Chen, Jian-Yi; Chen, San-Yuan

    2015-12-28

    We developed a surfactant-free method utilizing amifostine to stably link a targeting ligand (Herceptin) to amphiphilic gelatin (AG)-iron oxide@calcium phosphate (CaP) nanoparticles with hydrophobic curcumin (CUR) and hydrophilic doxorubicin (DOX) encapsulated in the AG core and CaP shell (AGIO@CaP-CD), respectively. This multi-functional nanoparticle system has a pH-sensitive CaP shell and degradable amphiphilic gelatin (AG) core, which enables controllable sequential release of the two drugs. The dual-targeting system of AGIO@CaP-CD (HER-AGIO@CaP-CD) with a bioligand and magnetic targeting resulted in significantly elevated cellular uptake in HER2-overexpressing SKBr3 cells and more efficacious therapy than delivery of targeting ligand alone due to the synergistic cell multi-drug resistance/apoptosis-inducing effect of the CUR and DOX combination. This nanoparticle combined with Herceptin and iron oxide nanoparticles not only provided a dual-targeting functionality, but also encapsulated CUR and DOX as a dual-drug delivery system for the combination therapy. This study further demonstrated that the therapeutic efficacy of this dual-targeting co-delivery system can be improved by modifying the application duration of magnetic targeting, which makes this combination therapy system a powerful new tool for in vitro/in vivo cancer therapy, especially for HER2-positive cancers.

  5. Nanoparticle vaccines.

    PubMed

    Zhao, Liang; Seth, Arjun; Wibowo, Nani; Zhao, Chun-Xia; Mitter, Neena; Yu, Chengzhong; Middelberg, Anton P J

    2014-01-01

    Nanotechnology increasingly plays a significant role in vaccine development. As vaccine development orientates toward less immunogenic "minimalist" compositions, formulations that boost antigen effectiveness are increasingly needed. The use of nanoparticles in vaccine formulations allows not only improved antigen stability and immunogenicity, but also targeted delivery and slow release. A number of nanoparticle vaccines varying in composition, size, shape, and surface properties have been approved for human use and the number of candidates is increasing. However, challenges remain due to a lack of fundamental understanding regarding the in vivo behavior of nanoparticles, which can operate as either a delivery system to enhance antigen processing and/or as an immunostimulant adjuvant to activate or enhance immunity. This review provides a broad overview of recent advances in prophylactic nanovaccinology. Types of nanoparticles used are outlined and their interaction with immune cells and the biosystem are discussed. Increased knowledge and fundamental understanding of nanoparticle mechanism of action in both immunostimulatory and delivery modes, and better understanding of in vivo biodistribution and fate, are urgently required, and will accelerate the rational design of nanoparticle-containing vaccines. PMID:24295808

  6. V3 Stain-free Workflow for a Practical, Convenient, and Reliable Total Protein Loading Control in Western Blotting

    PubMed Central

    Posch, Anton; Kohn, Jonathan; Oh, Kenneth; Hammond, Matt; Liu, Ning

    2013-01-01

    The western blot is a very useful and widely adopted lab technique, but its execution is challenging. The workflow is often characterized as a "black box" because an experimentalist does not know if it has been performed successfully until the last of several steps. Moreover, the quality of western blot data is sometimes challenged due to a lack of effective quality control tools in place throughout the western blotting process. Here we describe the V3 western workflow, which applies stain-free technology to address the major concerns associated with the traditional western blot protocol. This workflow allows researchers: 1) to run a gel in about 20-30 min; 2) to visualize sample separation quality within 5 min after the gel run; 3) to transfer proteins in 3-10 min; 4) to verify transfer efficiency quantitatively; and most importantly 5) to validate changes in the level of the protein of interest using total protein loading control. This novel approach eliminates the need of stripping and reprobing the blot for housekeeping proteins such as β-actin, β-tubulin, GAPDH, etc. The V3 stain-free workflow makes the western blot process faster, transparent, more quantitative and reliable. PMID:24429481

  7. The Solution Structure of a Nonribosomal Peptide Synthetase Carrier Protein Loaded with its Substrate Reveals Transient, Well-defined Contacts

    PubMed Central

    Goodrich, Andrew C.; Harden, Bradley J.; Frueh, Dominique P.

    2015-01-01

    Nonribosomal peptide synthetases (NRPSs) are microbial enzymes that produce a wealth of important natural products by condensing substrates in an assembly line manner. The proper sequence of substrates is obtained by tethering them to phosphopantetheinyl arms of holo carrier proteins (CPs) via a thioester bond. CPs in holo and substrate-loaded forms visit NRPS catalytic domains in a series of transient interactions. A lack of structural information on substrate-loaded carrier proteins has hindered our understanding of NRPS synthesis. Here, we present the first structure of an NRPS aryl carrier protein loaded with its substrate via a native thioester bond, together with the structure of its holo form. We also present the first quantification of NRPS CP backbone dynamics. Our results indicate that prosthetic moieties in both holo and loaded forms are in contact with the protein core, but they also sample states in which they are disordered and extend in solution. We observe that substrate loading induces a large conformational change in the phosphopantetheinyl arm, thereby modulating surfaces accessible for binding to other domains. Our results are discussed in the context of NRPS domain interactions. PMID:26334259

  8. A hierarchical porous bowl-like PLA@MSNs-COOH composite for pH-dominated long-term controlled release of doxorubicin and integrated nanoparticle for potential second treatment.

    PubMed

    Pan, Jianming; Wu, Runrun; Dai, Xiaohui; Yin, Yijie; Pan, Guoqing; Meng, Minjia; Shi, Weidong; Yan, Yongsheng

    2015-04-13

    We chemically integrated mesoporous silica nanoparticles (MSNs) and macroporous bowl-like polylactic acid (pBPLA) matrix, for noninvasive electrostatic loading and long-term controlled doxorubicin (DOX) release, to prepare a hierarchical porous bowl-like pBPLA@MSNs-COOH composite with a nonspherical and hierarchical porous structure. Strong electrostatic interaction with DOX rendered excellent encapsulation efficiency (up to 90.14%) to the composite. DOX release showed pH-dominated drug release kinetics; thus, maintaining a weak acidic pH (e.g., 5.0) triggered sustained release, suggesting the composite's great potential for long-term therapeutic approaches. In-vitro cell viability assays further confirmed that the composite was biocompatible and that the loaded drugs were pharmacologically active, exhibiting dosage-dependent cytotoxicity. Additionally, a wound-healing assay revealed the composite's intrinsic ability to inhibit cell migration. Moreover, pH- and time-dependent leaching of the integrated MSNs due to pBPLA matrix degradation allow us to infer that the leached (and drug loaded) MSNs may be engulfed by cancer cells contributing to a second wave of DOX-mediated cytotoxicity following pH-triggered DOX release.

  9. Calcium Carbonate Mineralized Nanoparticles as an Intracellular Transporter of Cytochrome c for Cancer Therapy.

    PubMed

    Koo, Ahn Na; Min, Kyung Hyun; Lee, Hong Jae; Jegal, Jun Ho; Lee, Jae Won; Lee, Sang Cheon

    2015-11-01

    A new intracellular delivery system based on an apoptotic protein-loaded calcium carbonate (CaCO3 ) mineralized nanoparticle (MNP) is described. Apoptosis-inducing cytochrome c (Cyt c) loaded CaCO3 MNPs (Cyt c MNPs) were prepared by block copolymer mediated in situ CaCO3 mineralization in the presence of Cyt c. The resulting Cyt c MNPs had a vaterite polymorph of CaCO3 with a mean hydrodynamic diameter of 360.5 nm and exhibited 60% efficiency for Cyt c loading. The Cyt c MNPs were stable at physiological pH (pH 7.4) and effectively prohibited the release of Cyt c, whereas, at intracellular endosomal pH (pH 5.0), Cyt c release was facilitated. The MNPs enable the endosomal escape of Cyt c for effective localization of Cyt c in the cytosols of MCF-7 cells. Flow cytometry showed that the Cyt c MNPs effectively induced apoptosis of MCF-7 cells. These findings indicate that the CaCO3 MNPs can meet the prerequisites for delivery of cell-impermeable therapeutic proteins for cancer therapy.

  10. In vitro apatite formation and drug loading/release of porous TiO2 microspheres prepared by sol-gel processing with different SiO2 nanoparticle contents.

    PubMed

    Kawashita, Masakazu; Tanaka, Yui; Ueno, Shoji; Liu, Gengci; Li, Zhixia; Miyazaki, Toshiki

    2015-05-01

    Bioactive titania (TiO2) microparticles can be used as drug-releasing cement fillers for the chemotherapeutic treatment of metastatic bone tumors. Porous anatase-type TiO2 microspheres around 15 μm in diameter were obtained through a sol-gel process involving a water-in-oil emulsion with 30:70 SiO2/H2O weight ratio and subsequent NaOH solution treatment. The water phase consisted of methanol, titanium tetraisopropoxide, diethanolamine, SiO2 nanoparticles, and H2O, while the oil phase consisted of kerosene, Span 80, and Span 60. The resulting microspheres had a high specific surface area of 111.7 m(2)·g(-1). Apatite with a network-like surface structure formed on the surface of the microspheres within 8 days in simulated body fluid. The good apatite-forming ability of the microspheres is attributed to their porous structure and the negative zeta potential of TiO2. The release of rhodamine B, a model for a hydrophilic drug, was rapid for the first 6 h of soaking, but diffusion-controlled thereafter. The burst release in the first 6h is problematic for clinical applications; nonetheless, the present results highlight the potential of porous TiO2 microspheres as drug-releasing cement fillers able to form apatite.

  11. In vitro apatite formation and drug loading/release of porous TiO2 microspheres prepared by sol-gel processing with different SiO2 nanoparticle contents.

    PubMed

    Kawashita, Masakazu; Tanaka, Yui; Ueno, Shoji; Liu, Gengci; Li, Zhixia; Miyazaki, Toshiki

    2015-05-01

    Bioactive titania (TiO2) microparticles can be used as drug-releasing cement fillers for the chemotherapeutic treatment of metastatic bone tumors. Porous anatase-type TiO2 microspheres around 15 μm in diameter were obtained through a sol-gel process involving a water-in-oil emulsion with 30:70 SiO2/H2O weight ratio and subsequent NaOH solution treatment. The water phase consisted of methanol, titanium tetraisopropoxide, diethanolamine, SiO2 nanoparticles, and H2O, while the oil phase consisted of kerosene, Span 80, and Span 60. The resulting microspheres had a high specific surface area of 111.7 m(2)·g(-1). Apatite with a network-like surface structure formed on the surface of the microspheres within 8 days in simulated body fluid. The good apatite-forming ability of the microspheres is attributed to their porous structure and the negative zeta potential of TiO2. The release of rhodamine B, a model for a hydrophilic drug, was rapid for the first 6 h of soaking, but diffusion-controlled thereafter. The burst release in the first 6h is problematic for clinical applications; nonetheless, the present results highlight the potential of porous TiO2 microspheres as drug-releasing cement fillers able to form apatite. PMID:25746276

  12. Controlled release of B-carotene in B-lactoglobulin-dextran conjugates nanoparticles in vitro digestion and the transport with Caco-2 monolayers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Undesirable aggregation of nanoparticles stabilized by proteins may may occur at the protein’s isoelectric point when the particle has zero net charge. Aggregation may be reduced bychanging the isoelectric point by conjugation of free amino groups with reducing sugars (Maillard reaction). Alternativ...

  13. Transport, retention, and long-term release behavior of ZnO nanoparticle aggregates in saturated quartz sand: Role of solution pH and biofilm coating

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The transport, retention, and long-term fate of zinc oxide nanoparticles (ZnO-NPs) were investigated in saturated, bare and biofilm (Pseudomonas putida) coated sand packed columns. Almost complete retention of ZnO-NPs occurred in bare and biofilm coated sand when the influent solution pH was 9 and t...

  14. Double-Cross-Linked Hyaluronic Acid Nanoparticles with pH/Reduction Dual-Responsive Triggered Release and pH-Modulated Fluorescence for Folate-Receptor-Mediated Targeting Visualized Chemotherapy.

    PubMed

    Zhao, Xubo; Jia, Xu; Liu, Lei; Zeng, Jin; Tian, Kun; Zhou, Tingting; Liu, Peng

    2016-04-11

    A versatile folate-receptor-mediated targeting tumor theranostics has been designed for pH/reduction dual-responsive controlled anticancer drug release and pH-modulated fluorescent tumor imaging via facile ionic (pH sensitive) and covalent (reduction responsive) double-cross-linking (DCL) of the folic acid (FA) and Rhodamine 6G modified hyaluronic acid (HA) (FA-HA-Rh 6G). After optimizing the morphology and diameter of the resultant nanoparticles (DCL FA-HA-Rh 6G NPs) via modulating the concentration of the ionic and covalent cross-linking agents, the one with Ca and S contents of 1.70 and 2.84 wt % and an average hydrodynamic diameter of 154 nm was chosen as the desired drug delivery system (DDS) for DOX. They not only had high drug loading capacity and drug encapsulation efficiency (716 ± 34 mg/g and 71.6 ± 3.4%) but also possessed perfect triggered release and strong fluorescence intensity in the stimulated tumor microenvironment. The MTT assay and CLSM analysis revealed that the proposed double-cross-linked HA-based DDS had favorable cytocompatibility and folate-receptor-mediated targeting functionality to the HeLa cells and could obviously enhance the anticancer efficiency of DOX. The integration of the pH and reduction dual-responsiveness, folate-receptor-mediated targeting functionality, and pH-dependent fluorescence intensity into the biodegradable and biocompatible HA nanoparticles make the DCL FA-HA-Rh 6G NPs significant potential for future visualized chemotherapy of cancers. PMID:27010934

  15. Influence of Hydrothermal Treatment on Physicochemical Properties and Drug Release of Anti-Inflammatory Drugs of Intercalated Layered Double Hydroxide Nanoparticles

    PubMed Central

    Gu, Zi; Wu, Aihua; Li, Li; Xu, Zhi Ping

    2014-01-01

    The synthesis method of layered double hydroxides (LDHs) determines nanoparticles’ performance in biomedical applications. In this study, hydrothermal treatment as an important synthesis technique has been examined for its influence on the physicochemical properties and the drug release rate from drug-containing LDHs. We synthesised MgAl–LDHs intercalated with non-steroidal anti-inflammatory drugs (i.e., naproxen, diclofenac and ibuprofen) using a co-precipitation method with or without hydrothermal treatment (150 °C, 4 h). After being hydrothermally treated, LDH–drug crystallites increased in particle size and crystallinity, but did not change in the interlayer anion orientation, gallery height and chemical composition. The drug release patterns of all studied LDH–drug hybrids were biphasic and sustained. LDHs loaded with diclofenac had a quicker drug release rate compared with those with naproxen and ibuprofen, and the drug release from the hydrothermally-treated LDH–drug was slower than the freshly precipitated LDH–drug. These results suggest that the drug release of LDH–drugs is influenced by the crystallite size of LDHs, which can be controlled by hydrothermal treatment, as well as by the drug molecular physicochemical properties. PMID:24858732

  16. In vivo labelling of hippocampal beta-amyloid in triple-transgenic mice with a fluorescent acetylcholinesterase inhibitor released from nanoparticles.

    PubMed

    Härtig, Wolfgang; Kacza, Johannes; Paulke, Bernd-Reiner; Grosche, Jens; Bauer, Ute; Hoffmann, Anke; Elsinghorst, Paul W; Gütschow, Michael

    2010-01-01

    The drastic loss of cholinergic projection neurons in the basal forebrain is a hallmark of Alzheimer's disease (AD), and drugs most frequently applied for the treatment of dementia include inhibitors of the acetylcholine-degrading enzyme acetylcholinesterase (AChE). This protein is known to act as a ligand of beta-amyloid (Abeta) in senile plaques, a further neuropathological sign of AD. Recently, we have shown that the fluorescent, heterodimeric AChE inhibitor PE154 allows for the histochemical staining of cortical Abeta plaques in triple-transgenic (TTG) mice with age-dependent beta-amyloidosis and tau hyperphosphorylation, an established animal model for aspects of AD. In the present study, we have primarily demonstrated the targeting of Abeta-immunopositive plaques with PE154 in vivo for 4 h up to 1 week after injection into the hippocampi of 13-20-month-old TTG mice. Numerous plaques, double-stained for PE154 and Abeta-immunoreactivity, were revealed by confocal laser-scanning microscopy. Additionally, PE154 targeted hippocampal Abeta deposits in aged TTG mice after injection of carboxylated polyglycidylmethacrylate nanoparticles delivering the fluorescent marker in vivo. Furthermore, biodegradable core-shell polystyrene/polybutylcyanoacrylate nanoparticles were found to be suitable, alternative vehicles for PE154 as a useful in vivo label of Abeta. Moreover, we were able to demonstrate that PE154 targeted Abeta, but neither phospho-tau nor reactive astrocytes surrounding the plaques. In conclusion, nanoparticles appear as versatile carriers of AChE inhibitors and other promising drugs for the treatment of AD.

  17. Potential release of in vivo trace metals from metallic medical implants in the human body: from ions to nanoparticles--a systematic analytical review.

    PubMed

    Matusiewicz, Henryk

    2014-06-01

    Metal ion release from metallic materials, e.g. metallic alloys and pure metals, implanted into the human body in dental and orthopedic surgery is becoming a major cause for concern. This review briefly provides an overview of both metallic alloys and pure metals used in implant materials in dental and orthopedic surgery. Additionally, a short section is dedicated to important biomaterials and their corrosive behavior in both real solutions and various types of media that model human biological fluids and tissues. The present review gives an overview of analytical methods, techniques and different approaches applied to the measurement of in vivo trace metals released into body fluids and tissues from patients carrying metal-on-metal prostheses and metal dental implants. Reference levels of ion concentrations in body fluids and tissues that have been determined by a host of studies are compiled, reviewed and presented in this paper. Finally, a collection of published clinical data on in vivo released trace metals from metallic medical implants is included.

  18. Protein-loaded microspheres prepared by sequential adsorption of dextran sulphate and protamine on melamine formaldehyde core.

    PubMed

    Balabushevich, Nadezda G; Larionova, Natalia I

    2009-11-01

    Polyelectrolyte multilayer microspheres were fabricated by layer-by-layer self-assembly of a dextran sulphate and a protamine on melamine formaldehyde cores, followed by the partial decomposition of the core. Effects of pH on the encapsulation of proteins and enzymes with different physico-chemical properties (insulin, aprotinin, peroxidase, glucose oxidase (GOD), catalase (Cat)) in the prepared microspheres were then studied. This method of protein encapsulation demonstrated a high loading capacity and efficiency. The protein incorporation and release was regulated by the pH of the solution. Encapsulated enzymes retained a high specific activity depending on the amount of protein incorporated. Bienzyme system GOD/Cat immobilized in the microspheres was suitable for the glucose content assay.

  19. Analyses of Endothelial Cells and Endothelial Progenitor Cells Released Microvesicles by Using Microbead and Q-dot Based Nanoparticle Tracking Analysis.

    PubMed

    Wang, Jinju; Zhong, Yun; Ma, Xiaotang; Xiao, Xiang; Cheng, Chuanfang; Chen, Yusen; Iwuchukwu, Ifeanyi; Gaines, Kenneth J; Zhao, Bin; Liu, Shiming; Travers, Jeffrey B; Bihl, Ji C; Chen, Yanfang

    2016-04-20

    Accurate analysis of specific microvesicles (MVs) from biofluids is critical and challenging. Here we described novel methods to purify and detect MVs shed from endothelial cells (ECs) and endothelial progenitor cells (EPCs) by combining microbeads with fluorescence quantum dots (Q-dots) coupled nanoparticle tracking analysis (NTA). In the in vitro screening systems, we demonstrated that 1) anti-CD105 (EC marker) and anti-CD34 (EPC marker) conjugated-microbeads had the highest sensitivity and specificity for isolating respective MVs, which were confirmed with negative controls, CD41 and CD235a; 2) anti-CD144 (EC marker) and anti-KDR (EPC marker) conjugated-Q-dots exhibited the best sensitivity and specificity for their respective MV NTA detection, which were confirmed with positive control, anti-Annexin V (MV universal marker). The methods were further validated by their ability to efficiently recover the known amount of EC-MVs and EPC-MVs from particle-depleted plasma, and to detect the dynamical changes of plasma MVs in ischemic stroke patients, as compared with traditional flow cytometry. These novel methods provide ideal approaches for functional analysis and biomarker discovery of ECs- and EPCs- derived MVs.

  20. Analyses of Endothelial Cells and Endothelial Progenitor Cells Released Microvesicles by Using Microbead and Q-dot Based Nanoparticle Tracking Analysis

    PubMed Central

    Wang, Jinju; Zhong, Yun; Ma, Xiaotang; Xiao, Xiang; Cheng, Chuanfang; Chen, Yusen; Iwuchukwu, Ifeanyi; Gaines, Kenneth J.; Bin Zhao; Liu, Shiming; Travers, Jeffrey B.; Bihl, Ji C.; Chen, Yanfang

    2016-01-01

    Accurate analysis of specific microvesicles (MVs) from biofluids is critical and challenging. Here we described novel methods to purify and detect MVs shed from endothelial cells (ECs) and endothelial progenitor cells (EPCs) by combining microbeads with fluorescence quantum dots (Q-dots) coupled nanoparticle tracking analysis (NTA). In the in vitro screening systems, we demonstrated that 1) anti-CD105 (EC marker) and anti-CD34 (EPC marker) conjugated-microbeads had the highest sensitivity and specificity for isolating respective MVs, which were confirmed with negative controls, CD41 and CD235a; 2) anti-CD144 (EC marker) and anti-KDR (EPC marker) conjugated-Q-dots exhibited the best sensitivity and specificity for their respective MV NTA detection, which were confirmed with positive control, anti-Annexin V (MV universal marker). The methods were further validated by their ability to efficiently recover the known amount of EC-MVs and EPC-MVs from particle-depleted plasma, and to detect the dynamical changes of plasma MVs in ischemic stroke patients, as compared with traditional flow cytometry. These novel methods provide ideal approaches for functional analysis and biomarker discovery of ECs- and EPCs- derived MVs. PMID:27094208

  1. Stem cell differentiation-related protein-loaded PLGA microspheres as a novel platform micro-typed scaffold for chondrogenesis.

    PubMed

    Park, Ji Sun; Lim, Hye-Jin; Yi, Se Won; Park, Keun-Hong

    2016-01-01

    During cell differentiation for tissue regeneration, several factors, including growth factors and proteins, influence cascades in stem cells such as embryonic stem cells and mesenchymal stem cells (MSCs). In this study, transforming growth factor (TGF)-β3 and SOX9, which is an important protein in chondrocytes, were used to generate mature chondrocytes from human MSCs (hMSCs). For safe and effective delivery of bioactive molecules into hMSCs, biodegradable poly-(d,l-lactide-co-glycolide) (PLGA) microspheres (MSs) were coated with TGF-β3 and loaded with SOX9. Instead of SOX9 protein, release of the model protein FITC-bovine serum albumin (BSA) from PLGA MS was evaluated in vitro and in vivo by confocal laser microscopy and Kodak imaging. The bioactivities of TGF-β3 and SOX9 were evaluated by assessing α-helical formation using circular dichroism. PLGA MS loaded with FITC-BSA easily entered hMSCs without causing cytotoxicity. To confirm that internalization of PLGA MSs harboring TGF-β3 and SOX9 induced chondrogenesis of hMSCs, we performed several molecular analyses. By analysis, the specific marker gene expression levels in hMSCs adhered onto PLGA MSs coated with TGF-β3 and loaded with SOX9 were more than 3-5 times that of the control group both in vitro and in vivo. This result revealed that PLGA MS uptake and subsequent release of SOX9 induced chondrogenesis of hMSCs was enhanced by coating PLGA MSs with TGF-β3. PMID:27586647

  2. Silver Nanoparticles in Dental Biomaterials

    PubMed Central

    Corrêa, Juliana Mattos; Mori, Matsuyoshi; Sanches, Heloísa Lajas; da Cruz, Adriana Dibo; Poiate, Isis Andréa Venturini Pola

    2015-01-01

    Silver has been used in medicine for centuries because of its antimicrobial properties. More recently, silver nanoparticles have been synthesized and incorporated into several biomaterials, since their small size provides great antimicrobial effect, at low filler level. Hence, these nanoparticles have been applied in dentistry, in order to prevent or reduce biofilm formation over dental materials surfaces. This review aims to discuss the current progress in this field, highlighting aspects regarding silver nanoparticles incorporation, such as antimicrobial potential, mechanical properties, cytotoxicity, and long-term effectiveness. We also emphasize the need for more studies to determine the optimal concentration of silver nanoparticle and its release over time. PMID:25667594

  3. Controlling protein release using biodegradable microparticles

    NASA Astrophysics Data System (ADS)

    Kline, Benjamin Patrick

    Research in the field of protein therapeutics has exploded over the past decade and continues to grow in both academia and in industry. Protein drugs have advantages of being highly specific and highly active making them coveted targets for high profile disease states like cancer and multiple sclerosis. Unfortunately, their many advantages are complemented by their obstacles. Because proteins are highly active and highly specific, the window between efficacy and toxicity is very narrow and drug development can be long and arduous. In addition, protein activity is dependent on its specific folding conformation that is easily disrupted by a variety of development processes. This research aimed to identify microparticle formulations to control protein release and also to determine which formulation parameters affected burst release, encapsulation, and steady-state release the most. It was found that polymer type and composition were two of the most important factors. Long-term controlled release of bovine serum albumin (BSA) was achieved as well as a wide variety of release profiles. A method was identified for micronizing protein at low cost to retain activity and coacervation was evaluated as a method for preparing protein loaded microspheres. This research provides a basis from which researchers can create better controlled release formulations for future protein therapeutics.

  4. Nanoparticles as synthetic vaccines.

    PubMed

    Smith, Josiah D; Morton, Logan D; Ulery, Bret D

    2015-08-01

    As vaccines have transitioned from the use of whole pathogens to only the required antigenic epitopes, unwanted side effects have been decreased, but corresponding immune responses have been greatly diminished. To enhance immunogenicity, a variety of controlled release vehicles have been proposed as synthetic vaccines, but nanoparticles have emerged as particularly impressive systems due to many exciting publications. In specific, nanoparticles have been shown capable of not only desirable vaccine release, but can also be targeted to immune cells of interest, loaded with immunostimulatory substances termed adjuvants, or even induce desirable immune activating effects on their own. In the present review, recent advances in the utilization of inorganic, polymeric, and biomolecular nanoparticles as synthetic vaccines are discussed.

  5. Sustained Nitric Oxide-Releasing Nanoparticles Induce Cell Death in Candida albicans Yeast and Hyphal Cells, Preventing Biofilm Formation In Vitro and in a Rodent Central Venous Catheter Model

    PubMed Central

    Ahmadi, Mohammed S.; Lee, Hiu Ham; Sanchez, David A.; Friedman, Adam J.; Tar, Moses T.; Davies, Kelvin P.; Nosanchuk, Joshua D.

    2016-01-01

    Candida albicans is a leading nosocomial pathogen. Today, candidal biofilms are a significant cause of catheter infections, and such infections are becoming increasingly responsible for the failure of medical-implanted devices. C. albicans forms biofilms in which fungal cells are encased in an autoproduced extracellular polysaccharide matrix. Consequently, the enclosed fungi are protected from antimicrobial agents and host cells, providing a unique niche conducive to robust microbial growth and a harbor for recurring infections. Here we demonstrate that a recently developed platform comprised of nanoparticles that release therapeutic levels of nitric oxide (NO-np) inhibits candidal biofilm formation, destroys the extracellular polysaccharide matrices of mature fungal biofilms, and hinders biofilm development on surface biomaterials such as the lumen of catheters. We found NO-np to decrease both the metabolic activity of biofilms and the cell viability of C. albicans in vitro and in vivo. Furthermore, flow cytometric analysis found NO-np to induce apoptosis in biofilm yeast cells in vitro. Moreover, NO-np behave synergistically when used in combination with established antifungal drug therapies. Here we propose NO-np as a novel treatment modality, especially in combination with standard antifungals, for the prevention and/or remediation of fungal biofilms on central venous catheters and other medical devices. PMID:26810653

  6. Nitric Oxide Releasing Nanoparticles prevent Propionibacterium acnes induced inflammation by both clearing the organism and inhibiting microbial stimulation of the innate immune response