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Sample records for release protein-loaded nanoparticles

  1. 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

  2. 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. PMID:21639993

  3. 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

  4. 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

  5. Continuous separation of protein loaded nanoparticles by simulated moving bed chromatography.

    PubMed

    Satzer, Peter; Wellhoefer, Martin; Jungbauer, Alois

    2014-07-01

    For scale up and efficient production of protein loaded nanoparticles continuous separation by size exclusion chromatography in simulated moving bed (SMB) mode helps do reduce unbound protein concentration and increase yields for perfectly covered particles. Silica nanoparticles were loaded with an excess of beta casein or bovine serum albumin (BSA) and the loaded particles purified by size exclusion chromatography using Sephacryl300 as stationary phase in a four zone SMB. We determined our working points for the SMB from batch separations and the triangle theory described by Mazzotti et al. with an SMB setup of one Sephacryl300 26/70mm column per zone with switch times of 5min for BSA and 7min for beta casein. In the case of BSA the Raffinate contained loaded nanoparticles of 63% purity with 98% recovery and the extract was essentially particle free (95% purity). We showed that the low purity of the Raffinate was only due to BSA multimers present in the used protein solution. In the case of beta casein where no multimers are present we achieved 89% purity and 90% recovery of loaded nanoparticles in the Raffinate and an extract free of particles (92% purity). Using a tangential flow filtration unit with 5kDa cutoff membrane we proved that the extract can be concentrated for recycling of protein and buffer. The calculated space-time-yield for loaded nanoparticles was 0.25g of loaded nanoparticles per hour and liter of used resin. This proves that the presented process is suitable for large scale production for industrial purposes. PMID:24866563

  6. Understanding the quality of protein loaded PLGA nanoparticles variability by Plackett–Burman design

    PubMed Central

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

    2011-01-01

    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) (X1), PLGA (X2), and emulsifier concentration namely SLS (X3), stirring rate (X4), type of organic solvent employed (chloroform or dichloromethane, X5) and organic to aqueous phase ratio (X6). The nanoparticles properties considered were encapsulation efficiency (Y1), mean particle size (Y2), zeta potential (Y3), burst effect (Y4) and dissolution efficiency (Y5). 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 (Y1), mean particle size (Y2) and zeta potential (Y3) from 10.17% to 93.01%, 41.60 to 372.80nm 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 (Y5) 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. PMID:20038446

  7. A novel technology using transscleral ultrasound to deliver protein loaded nanoparticles.

    PubMed

    Huang, Di; Wang, Lili; Dong, Yixuan; Pan, Xin; Li, Ge; Wu, Chuanbin

    2014-09-01

    This study was designed to investigate the feasibility of silk fibroin nanoparticles (SFNs) for sustained drug delivery in transscleral ultrasound. Fluorescein isothiocynate labeled bovine serum albumin (FITC-BSA, MW 66.45 kDa) was chosen as a model macromolecular protein drug and SFNs were used as nano-carrier systems suitable for ocular drug delivery. Drug loaded nanoparticles (FITC-BSA-SFNs) were first prepared and characterized. In vitro transscleral study under ultrasound exposure (1MHz, 0.5 W/cm(2), 5 min continuous wave) using isolated sclera of rabbit was performed. The posterior eye segment of rabbit was examined for adverse effect by slit-lamp and histology. It was found that FITC-BSA-SFNs possessed sustained release, bioadhesive, and co-permeation characteristics. The ultrasound application significantly improved the penetration efficiency of FITC-BSA-SFNs as compared with passive delivery, meanwhile caused no damages to the ocular tissue and particles themselves. The distribution profile of SFNs revealed rapid and lasting adhesion on the outer scleral tissues, followed by migration into the interior up to one week after treatment. This research suggested a novel non-invasive transscleral administration of macromolecular protein drugs using SFN carriers combining with ultrasound technology. PMID:24833007

  8. Timed-release polymer nanoparticles.

    PubMed

    Tran, Nguyen T D; Truong, Nghia P; Gu, Wenyi; Jia, Zhongfan; Cooper, Matthew A; Monteiro, Michael J

    2013-02-11

    Triggered-release of encapsulated therapeutics from nanoparticles without remote or environmental triggers was demonstrated in this work. Disassembly of the polymer nanoparticles to unimers at precise times allowed the controlled release of oligo DNA. The polymers used in this study consisted of a hydrophilic block for stabilization and second thermoresponsive block for self-assembly and disassembly. At temperatures below the second block's LCST (i.e., below 37 °C for in vitro assays), the diblock copolymer was fully water-soluble, and when heated to 37 °C, the polymer self-assembled into a narrow size distribution of nanoparticles with an average diameter of approximately 25 nm. The thermoresponsive nature of the second block could be manipulated in situ by the self-catalyzed degradation of cationic 2-(dimethylamino)ethyl acrylate (DMAEA) units to negatively charged acrylic acid groups and when the amount of acid groups was sufficiently high to increase the LCST of the second block above 37 °C. The disassembly of the nanoparticles could be controlled from 10 to 70 h. The use of these nanoparticles as a combined therapy, in which one or more agents can be released in a predetermined way, has the potential to improve the personal point of care treatment of patients. PMID:23298322

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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

  17. Polymer Coated Echogenic Lipid Nanoparticles with Dual Release Triggers

    PubMed Central

    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

    2013-01-01

    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 minutes 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. PMID:23394107

  18. 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

  19. 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. PMID:25534673

  20. Novel Thermogelling Dispersions of Polymer Nanoparticles for Controlled Protein Release

    PubMed Central

    Cai, Tong; Hu, Peter D.; Sun, Manwu; Zhou, Jun; Tsai, Yi-Ting; Baker, David; Tang, Liping

    2012-01-01

    A novel poly(oligo(ethylene glycol) methyl ether methacrylate-co-oligo(ethylene glycol) ethyl ether methacrylate)/ poly(acrylic acid) interpenetrating network (IPN) nanoparticle was synthesized. The temperature-responsive properties of the IPN nanoparticles were investigated by dynamic light scattering method. Atomic force microscopic images confirm the homogenous and mono-disperse morphology of the IPN nanoparticles. Both visual observation and viscosity testing demonstrated that the IPN nanoparticles exhibit thermogelling properties at body temperature, 37°C. Subsequent studies verified that such temperature sensitive properties of IPN nanoparticles allow their ease of injection and then slow release of model proteins, both in vitro and in vivo. Histological analysis showed that our IPN implants exerted minimal inflammation following subcutaneous implantation. Our results support that, by simply mixing with proteins of interest, the novel IPN nanoparticles can be used to form in situ thermogelling devices for controlled protein release. PMID:22349097

  1. 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.

  2. 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.

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

    PubMed

    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

  4. 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

  5. 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. PMID:26093234

  6. 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

  7. Thermosensitive liposomes entrapping iron oxide nanoparticles for controllable drug release.

    PubMed

    Tai, Lin-Ai; Tsai, Pi-Ju; Wang, Yu-Chao; Wang, Yu-Jing; Lo, Leu-Wei; Yang, Chung-Shi

    2009-04-01

    Iron oxide nanoparticles can serve as a heating source upon alternative magnetic field (AMF) exposure. Iron oxide nanoparticles can be mixed with thermosensitive nanovehicles for hyperthermia-induced drug release, yet such a design and mechanism may not be suitable for controllable drug release applications in which the tissues are susceptible to environmental temperature change such as brain tissue. In the present study, iron oxide nanoparticles were entrapped inside of thermosensitive liposomes for AMF-induced drug release while the environmental temperature was maintained at a constant level. Carboxyfluorescein was co-entrapped with the iron oxide nanoparticles in the liposomes as a model compound for monitoring drug release and environmental temperature was maintained with a water circulator jacket. These experiments have been successfully performed in solution, in phantom and in anesthetized animals. Furthermore, the thermosensitive liposomes were administered into rat forearm skeletal muscle, and the release of carboxylfluorescein triggered by the external alternative magnetic field was monitored by an implanted microdialysis perfusion probe with an on-line laser-induced fluorescence detector. In the future such a device could be applied to simultaneous magnetic resonance imaging and non-invasive drug release in temperature-sensitive applications. PMID:19420485

  8. Ocular Sustained Release Nanoparticles Containing Stereoisomeric Dipeptide Prodrugs of Acyclovir

    PubMed Central

    Jwala, Jwala; Boddu, Sai H.S.; Shah, Sujay; Sirimulla, Suman; Pal, Dhananjay

    2011-01-01

    Abstract Purpose The objective of this study was to develop and characterize polymeric nanoparticles of appropriate stereoisomeric dipeptide prodrugs of acyclovir (L-valine-L-valine-ACV, L-valine-D-valine-ACV, D-valine-L-valine-ACV, and D-valine-D-valine-ACV) for the treatment of ocular herpes keratitis. Methods Stereoisomeric dipeptide prodrugs of acyclovir (ACV) were screened for bioreversion in various ocular tissues, cell proliferation, and uptake across the rabbit primary corneal epithelial cell line. Docking studies were carried out to examine the affinity of prodrugs to the peptide transporter protein. Prodrugs with optimum characteristics were selected for the preparation of nanoparticles using various grades of poly (lactic-co-glycolic acid) (PLGA). Nanoparticles were characterized for the entrapment efficiency, surface morphology, size distribution, and in vitro release. Further, the effect of thermosensitive gels on the release of prodrugs from nanoparticles was also studied. Results L-valine-L-valine-ACV and L-valine-D-valine-ACV were considered to be optimum in terms of enzymatic stability, uptake, and cytotoxicity. Docking results indicated that L-valine in the terminal position increases the affinity of the prodrugs to the peptide transporter protein. Entrapment efficiency values of L-valine-L-valine-ACV and L-valine-D-valine-ACV were found to be optimal with PLGA 75:25 and PLGA 65:35 polymers, respectively. In vitro release of prodrugs from nanoparticles exhibited a biphasic release behavior with initial burst phase followed by sustained release. Dispersion of nanoparticles in thermosensitive gels completely eliminated the burst release phase. Conclusion Novel nanoparticulate systems of dipeptide prodrugs of ACV suspended in thermosensitive gels may provide sustained delivery after topical administration. PMID:21500985

  9. 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

  10. 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

  11. Effect of nanoparticles on kinetics release and fractionation of phosphorus.

    PubMed

    Taghipour, Marzieh; Jalali, Mohsen

    2015-01-01

    In this study, we examined the effect of nanoparticles (Al2O3 and TiO2) on kinetics release, fractionation and speciation of phosphorus (P) in some calcareous soils of western Iran. The maximum (average of five soils) (40.3 mg kg(-1)) and the minimum (10.5 mg kg(-1)) P were released by control soils and soils plus 3% TiO2, respectively. Pseudo second-order model described well P release. In order to predict and model the effects of NPs on P release, surface complexation model in PHREEQC program was used. The model could simulate the P release very well in all soils. After P release, the percentage of organic matter and sulphide-P fraction increased markedly following NPs addition, while carbonated-P fraction remained the most dominant fraction in all soils. In the initial stage of P release the solution samples in all soils and treatments were saturated with respect to strengite, and undersaturated with respect to other phosphate minerals. At the end of P release, all solutions were saturated with respect to hydroxyapatite and strengite and undersaturated with respect to other phosphate minerals. These results reflected that the NPs caused immobilization of P in soils and reduced the bioavailable P, thus, reducing their environment risk. PMID:25306535

  12. 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.

  13. 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.

  14. 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).

  15. 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

  16. 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

  17. 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

  18. 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

  19. PLA/PLGA nanoparticles for sustained release of docetaxel.

    PubMed

    Musumeci, T; Ventura, C A; Giannone, I; Ruozi, B; Montenegro, L; Pignatello, R; Puglisi, G

    2006-11-15

    This study investigates the potentiality of nanosphere colloidal suspensions as sustained release systems for intravenous administration of docetaxel (DTX). Nanospheres were prepared by solvent displacement method using polylactic acids (PLA) at different molecular weight and polylactic-co-glycolic (PLGA) as biodegradable matrices. The systems were characterized by light scattering analysis for their mean size, size distribution and zeta potential and by scanning electron microscopy (SEM) for surface morphology. The average diameters of the nanoparticles ranged from 100 to 200 nm. Negative zeta potential values were observed for all systems, particularly the nanospheres produced with the lowest molecular weight PLA showed a zeta potential value of -28mV. Differential scanning calorimetry analysis (DSC) suggested that DTX was molecularly dispersed in the polymeric matrices. A biphasic release of DTX was observed for all colloidal suspensions, after a burst effect in which about 50% (w/w) of the loaded drug was released a sustained release profile for about 10 days was observed. To evaluate the influence of the polymeric carrier on the interaction of DTX with biological membranes, we performed an in vitro study using lipid vesicles made of dipalmitoylphosphatidylcholine (DPPC) as a biomembrane model. DSC was used as a simple and not invasive technique of analysis. DTX produced a depression of DPPC pretransition peak, no variation of the main phase transition temperature and a significative increase of DeltaH value, showing a superficial penetration of the drug into DPPC bilayer. Kinetic experiments demonstrated that the release process of DTX form nanospheres is affected by the molecular weight of the employed polymers. PMID:16887303

  20. Chemokine-Releasing Nanoparticles for Manipulation of Lymph Node Microenvironment

    PubMed Central

    Popova, Taissia G.; Teunis, Allison; Magni, Ruben; Luchini, Alessandra; Espina, Virginia; Liotta, Lance A.; Popov, Serguei G.

    2015-01-01

    Chemokines (CKs) secreted by the host cells into surrounding tissue establish concentration gradients directing the migration of leukocytes. We propose an in vivo CK gradient remodeling approach based on sustained release of CKs by the crosslinked poly(N-isopropylacrylamide) hydrogel open meshwork nano-particles (NPs) containing internal crosslinked dye affinity baits for a reversible CK binding and release. The sustained release is based on a new principle of affinity off-rate tuning. The NPs with Cibacron Blue F3G-A and Reactive Blue-4 baits demonstrated a low-micromolar affinity binding to IL-8, MIP-2, and MCP-1 with a half-life of several hours at 37°C. The capacity of NPs loaded with IL-8 and MIP-1α to increase neutrophil recruitment to lymph nodes (LNs) was tested in mice after footpad injection. Fluorescently-labeled NPs used as tracers indicated the delivery into the sub-capsular compartment of draining LNs. The animals administered the CK-loaded NPs demonstrated a widening of the sub-capsular space and a strong lymph node influx of leukocytes, while mice injected with control NPs without CKs or bolus doses of soluble CKs alone showed only a marginal neutrophil response. This technology provides a new means therapeutically direct or restore immune cell traffic, and can also be employed for simultaneous therapy delivery. PMID:25878893

  1. 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.

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

    PubMed Central

    2014-01-01

    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. PMID:25114637

  3. 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.

  4. 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

  5. Fabrication and evaluation of the novel reduction-sensitive starch nanoparticles for controlled drug release.

    PubMed

    Yang, Jinlong; Huang, Yinjuan; Gao, Chunmei; Liu, Mingzhu; Zhang, Xinjie

    2014-03-01

    A novel type of reduction-sensitive starch nanoparticles was prepared via the reversed-phase microemulsion method by using crosslinker, N,N-bisacryloylcystamine (BAC) with the disulfide linkages, which was specifically cleaved by dithiothreitol (DTT). Starch nanoparticles had a spherical morphology with a small size of 40 nm in the optimal condition. The influences of process parameters (starch amount, surfactant amount and oil/water (O/W) ratio) on the size of starch nanoparticles were studied by dynamic light scattering (DLS). BAC crosslinked starch nanoparticles were degraded into oligomers with the reducing agent of DTT due to the cleavage of the disulfide linkages. A model drug 5-aminosalicylic acid (5-ASA) could be loaded efficiently into starch nanoparticles and the in vitro drug release behaviors were also studied. The results suggested that the disulfide crosslinked starch nanoparticles exhibited an accelerated drug release behavior in the presence of DTT. In vitro methyl thiazolyl tetrazolium (MTT) assays indicated that BAC crosslinked starch nanoparticles had a good biocompatibility when cocultured with human HeLa cancer cells. Hence, with excellent biocompatibility and biodegradability, and rapid drug release in response to DTT, BAC crosslinked starch nanoparticles showed a great potential as a biomaterial carrier for the application of drug controlled release. In contrast to BAC crosslinked starch nanoparticles, N,N-methylenebisacrylamine (MBA) crosslinked starch nanoparticles were prepared as the control without the disulfide linkages. PMID:24463097

  6. Glutathione-mediated release of Bodipy® from PEG cofunctionalized gold nanoparticles

    PubMed Central

    Kumar, Dhiraj; Meenan, Brian J; Dixon, Dorian

    2012-01-01

    Gold nanoparticles synthesized via sodium citrate reduction of chloroauric acid (HAuCl4) were functionalized with either various concentrations of thiol-terminated Bodipy® FL L-cystine (0.5, 1.0, 1.5, and 2.0 μg/mL) or Bodipy-poly(ethylene glycol) at concentrations of 0.5–18.75, 1.0–12.50, and 1.5–6.25 μg/mL to form a mixed monolayer of BODIPY-PEG. Thiol-terminated Bodipy, a fluorescing molecule, was used as the model drug, while PEG is widely used in drug-delivery applications to shield nanoparticles from unwanted immune responses. Understanding the influence of PEG-capping on payload release is critical because it is the most widely used type of nanoparticle functionalization in drug delivery studies. It has been previously reported that glutathione can trigger release of thiol-bound payloads from gold nanoparticles. Bodipy release from Bodipy capped and from Bodipy-PEG functionalized gold nanoparticles was studied at typical intracellular glutathione levels. It was observed that the addition of PEG capping inhibits the initial burst release observed in gold nanoparticles functionalized only with Bodipy and inhibits nanoparticle aggregation. Efficient and controlled payload release was observed in gold nanoparticles cofunctionalized with only a limited amount of PEG, thus enabling the coattachment of large amounts of drug, targeting groups or other payloads. PMID:22915847

  7. 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

    2016-05-11

    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

  8. 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 ...

  9. 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. PMID:22356870

  10. 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

  11. 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

  12. 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. PMID:25661378

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

    PubMed Central

    2014-01-01

    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. PMID:25114635

  14. 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.

  15. Biomimetic synthesis of hybrid hydroxyapatite nanoparticles using nanogel template for controlled release of bovine serum albumin.

    PubMed

    Qin, Jinli; Zhong, Zhenyu; Ma, Jun

    2016-05-01

    A biomimetic method was used to prepare hybrid hydroxyapatite (HAP) nanoparticles with chitosan/polyacrylic acid (CS-PAA) nanogel. The morphology, structure, crystallinity, thermal properties and biocompatibility of the obtained hybrid nanogel-HAP nanoparticles have been characterized. In addition, bovine serum albumin (BSA) was used as a model protein to study the loading and release behaviors of the hybrid nanogel-HAP nanoparticles. The results indicated that the obtained HAP nanoparticles were agglomerated and the nanogel could regulate the formation of HAP. When the nanogel concentration decreased, different HAP crystal shapes and agglomerate structures were obtained. The loading amount of BSA reached 67.6 mg/g for the hybrid nanoparticles when the mineral content was 90.4%, which decreased when the nanogel concentration increased. The release profile of BSA was sustained in neutral buffer. Meanwhile, an initial burst release was found at pH 4.5 due to the desorption of BSA from the surface, followed by a slow release. The hemolysis percentage of the hybrid nanoparticles was close to the negative control, and these particles were non-toxic to bone marrow stromal stem cells. The results suggest that these hybrid nanogel-HAP nanoparticles are promising candidate materials for biocompatible drug delivery systems. PMID:26952436

  16. 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.

  17. Synthesis, characterization, and controllable drug release of pH-sensitive hybrid magnetic nanoparticles

    NASA Astrophysics Data System (ADS)

    Zhou, Lilin; Yuan, Jinying; Yuan, Weizhong; Sui, Xiaofeng; Wu, Sizhu; Li, Zhaolong; Shen, Dezhong

    2009-09-01

    The synthesis of magnetite nanoparticles coated with pH-sensitive poly((2-dimethylamino) ethyl methacrylate) (PDMAEMA) via atom transfer radical polymerization (ATRP) for use as novel potential carriers for targeted drug delivery and controllable release is reported. The organic/inorganic hybrid nanoparticles were obtained with a narrow molecular weight distribution. The pH-sensitivity of the nanoparticles was investigated by the measurement of the pH dependence of hydrodynamic radius and the superparamagnetism was illustrated by vibrating sample magnetometer (VSM). The behavior of model drug phenolphthalein released from the nanoparticles indicated that the rate of drug release could be effectively controlled by altering the pH values of the environment.

  18. 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

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

    PubMed Central

    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

  20. Multi-layered polymeric nanoparticles for pH-responsive and sequenced release of theranostic agents.

    PubMed

    Wang, Hai; Zhao, Shuting; Agarwal, Pranay; Dumbleton, Jenna; Yu, Jianhua; Lu, Xiongbin; He, Xiaoming

    2015-05-01

    In this study, multi-layered pH-responsive polymeric nanoparticles (NPs) are prepared by multiple (up to 4) emulsifications to encapsulate multiple hydrophilic and hydrophobic theranostic agents for controlled and sequenced release. It is found that the sequence of release of multiple chemotherapeutic agents from the NPs significantly affects their efficacy against cancer cells. PMID:25850616

  1. Antibacterial releasing titanium surface using albumin nanoparticle carriers.

    PubMed

    Kim, Da Hye; Kim, Kyo-Han; Kwon, Tae-Yub; Choi, Seok Hwa; Kang, Seong Soo; Kwon, Soon-Taek; Cho, Dae-Hyun; Kim, Hee Dong; Son, Jun Sik

    2014-11-01

    We developed a simple and highly efficient method for delivery from titanium (Ti) surfaces using albumin nanoparticle carriers. A Ti disc with a resorbable blasting media surface was used as a metal implant with a localized drug delivery structure. Human serum albumin (HSA) nanoparticles loaded with chlorhexidine (CHX) diacetate salt hydrate as the model drug were fabricated using a desolvation technique. The CHX-loaded HSA nanoparticles produced were cross linked with glutaraldehyde (GA). The nanoparticles were pre-coated with positively-charged polyethylenimine (PEI) molecules and then immobilized via electrical interactions on the negatively charged Ti disc surface. Our results suggested that the PEI-coated HSA nanoparticles loaded with CHX (PEI-CHX-HSA) were incorporated successfully and well-dispersed on the Ti disc surfaces. The agar diffusion test on the Ti surface treated with PEI-CHX-HSA nanoparticles showed a larger growth inhibition zone of Streptococcus mutans versus the control Ti surface, suggesting that this innovative delivery platform imparts potent antibacterial activity to the Ti surface. Thus, CHX, which inhibits the growth of oral bacteria, can be efficiently incorporated onto Ti surfaces by using HSA nanoparticles. PMID:25958539

  2. 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

  3. 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

  4. Clean Photothermal Heating and Controlled Release from Near-Infrared Dye Doped Nanoparticles without Oxygen Photosensitization.

    PubMed

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

    2015-07-21

    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 (1)O2 and no photobleaching of the dye). In contrast, laser-induced heating of nanoparticles containing ICG or IR780 produced reactive (1)O2, leading to bleaching of the dye and also decomposition of coencapsulated 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

  5. Protease degradable tethers for controlled and cell-mediated release of nanoparticles in 2- and 3-dimensions

    PubMed Central

    Tokatlian, Talar; Shrum, Chadwick T.; Kadoya, Warren M.; Segura, Tatiana

    2010-01-01

    Strategies to control the release rate of bioactive signals from tissue engineering scaffolds are essential for tissue regeneration and tissue engineering applications. Here we report on a strategy to achieve temporal control over nanoparticle release from biomaterials using cell-secreted proteases. This cell-triggered release approach utilizes peptides that are degraded by matrix metalloproteinases (MMPs) at different rates to immobilize nanoparticles directly to the biomaterial surface. Thus, the peptide-immobilized nanoparticles are released with temporal control through the action of cell-released MMPs. We found that release rates of peptide-immobilized nanoparticles were a function of peptide sensitivity to proteases, the number of tethers between the nanoparticle and the surface and the concentration of proteases used to induce release. Cellular internalization of the peptide-immobilized nanoparticles was also a function of the peptide sensitivity to proteases, the number of tethers between the nanoparticle and the surface and MMP expression profile of the cells. Similar trends were observed for peptide-immobilized nanoparticles inside micro-porous hydrogels, indicating protease sensitive tethers are effective in controlling release rate and internalization of nanoparticles. Such a temporal delivery strategy of nanoparticles loaded with therapeutic payloads (e.g. protein, DNA, siRNA) can be an ideal means to guide tissue formation. PMID:20688389

  6. Characterization of abrasion-induced nanoparticle release from paints into liquids and air

    NASA Astrophysics Data System (ADS)

    Golanski, L.; Gaborieau, A.; Guiot, A.; Uzu, G.; Chatenet, J.; Tardif, F.

    2011-07-01

    Two standard methods for the characterization of the abrasion nanoparticle release into air and liquid from coatings containing nanoparticles were developed. Details of the abrasion processes and the measurement methods are shown. Paints were formulated in an industrial facility. Standard abrasion conditions in wet environments were simulated. The size distribution of the particles abraded into liquid was analyzed by a laser granulometer: submicrometric and micrometric particles were observed, but no nanometric particles. The nanoparticles released in liquid were deposited on filters for SEM (Scanning Electron Microscopy) analysis. No free or agglomerated nanoparticles were observed by SEM: nanoparticles seem to remain embedded in the paint matrix. The same coatings were abraded in the air using another standard method. The ELPI (Electrical Low Pressure Impactor) was used to determine the number size distribution of the dust generated. Abrasion is found to produce submicrometric and micrometric particles in the air but no nanoparticles. Further characterizations by SEM confirmed that no free or agglomerated nanoparticles were emitted: nanoparticles seem to remain embedded in the paint matrix.

  7. Influence of Scaffold Size on Bactericidal Activity of Nitric Oxide Releasing Silica Nanoparticles

    PubMed Central

    Carpenter, Alexis W.; Slomberg, Danielle L.; Rao, Kavitha S.; Schoenfisch, Mark H.

    2011-01-01

    A reverse microemulsion synthesis was used to prepare amine functionalized silica nanoparticles of three distinct sizes (i.e., 50, 100, and 200 nm) with identical amine concentrations. The resulting hybrid nanoparticles, consisting of N-(6 aminohexyl) aminopropyltrimethoxysilane and tetraethoxysilane, were highly monodisperse in size. N-diazeniumdiolate nitric oxide (NO) donors were subsequently formed on secondary amines while controlling reaction conditions to keep the total amount of nitric oxide (NO) released constant for each particle size. The bactericidal efficacy of the NO releasing nanoparticles against Pseudomonas aeruginosa increased with decreasing particle size. Additionally, smaller diameter nanoparticles were found to associate with the bacteria at a faster rate and to a greater extent than larger particles. Neither control (non-NO-releasing) nor NO releasing particles exhibited toxicity towards L929 mouse fibroblasts at concentrations above their respective minimum bactericidal concentrations. This study represents the first investigation of the bactericidal efficacy of NO-releasing silica nanoparticles as a function of particle size. PMID:21842899

  8. 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

  9. 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

  10. Multifluorescently traceable nanoparticle by a single-wavelength excitation with color-related drug release performance.

    PubMed

    Lu, Deli; Lei, Juying; Wang, Lingzhi; Zhang, Jinlong

    2012-05-30

    Monodisperse and nanometer-sized periodic mesoporous organosilicas co-doped with fluorescence resonance energy transfer cascades composed of triple fluorophores at various ratios were prepared. These nanoparticles exhibit multifluorescent emissions by a single-wavelength excitation and were designed for the application as multichannelly traceable drug carriers. Different from the hydrophilic framework of inorganic mesoporous silica and hydrophobic framework of mesoporous carbon, these multifluorescent nanoparticles have intrinsically different and finely tunable pore surface polarities governed by the type and amount of fluorophore inside the framework. When applied as drug carriers, they can achieve synchronous or asynchronous release of different drugs by simply choosing different colored nanoparticles. These colorful mesoporous composites with finely tunable color-related drug release performance provide a strong barcoding system for the potential applications of fluorescent nanoparticles in effective screening of drugs and therapeutic protocols for diseases. PMID:22591275

  11. Modelling irradiation by EM waves of multifunctionalized iron oxide nanoparticles and subsequent drug release

    NASA Astrophysics Data System (ADS)

    Wang, Feng; Calvayrac, Florent; Montembault, Véronique; Fontaine, Laurent

    2015-09-01

    Thermal transport in the environment close to the periphery of the nanoparticle, from a few angstroms to less than a nanometer scale, is becoming increasingly important with the advent of several biomedical applications of multifunctional magnetic nanoparticles, including drug delivery, magnetic resonance imaging, and hyperthermia therapy. We present a multiscale and multiphysics model of the irradiation by electromagnetic waves of radiofrequency of iron oxide nanoparticles functionalized by drug-releasing polymers used as new multifunctional therapeutic compounds against tumors. We compute ab initio the thermal conductivity of the polymer chains as a function of the length, model the unfolding of the polymer after heat transfer from the nanoparticle by molecular mechanics, and develop a multiscale thermodynamic and heat transfer model including the surrounding medium (water) in order to model the drug release.

  12. Polymer-coated mesoporous silica nanoparticles for the controlled release of macromolecules.

    PubMed

    Bhattacharyya, Sanjib; Wang, Henson; Ducheyne, Paul

    2012-09-01

    With the goal of achieving constant release of large biological molecules over an extended period of time we focused on hybrid inorganic/organic nanoparticles. We synthesized poly(ethylene glycol) (PEG)-coated mesoporous silica nanoparticles (MSNs) with incorporated trypsin inhibitor (TI), a model protein molecule for growth factors. Due to the goal of incorporating large protein molecules the pore size of the as-synthesized MSNs was expanded by a hydrothermal treatment prior to TI incorporation. In vitro release from the MSNs without the thin polymer film shows an initial burst followed by continuous release. In the case of polymer-coated MSNs the initial burst release was completely suppressed and approximate zero order release was achieved for 4 weeks. PMID:22688089

  13. 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

  14. 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

  15. 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. PMID:20696941

  16. Anticancer Efficacies of Cisplatin-Releasing pH-Responsive Nanoparticles

    PubMed Central

    Xu, Peisheng; Van Kirk, Edward A.; Murdoch, William J.; Zhan, Yihong; Isaak, Dale D.; Radosz, Maciej; Shen, Youqing

    2008-01-01

    The objective of these investigations was to test the hypothesis that a rapid cytoplasmic release profile from nanoparticles would potentiate the anticancer activity of cisplatin. Cisplatin-loaded nanoparticles with pH-responsive poly[2-(N,N-diethylamino)ethyl methacrylate] (PDEA) cores were synthesized from PDEA-block-poly(ethylene glycol) (PDEA-PEG) copolymer using a solvent-displacement (acetone-water) method. Nanoparticles with pH-nonresponsive poly(ε-caprolactone) (PCL) cores made from PCL-block-PEG (PCL-PEG) were used for comparison. Nanoparticle sizes, zeta-potentials, drug-loading capacities, and pH responsiveness were characterized. The cellular uptakes and localization in lysosomes were visualized using confocal fluorescence microscopy. Cytostatic effects of free and encapsulated cis-diammineplatinum(II) dichloride (cisplatin) toward human SKOV-3 epithelial ovarian cancer cells were estimated using the MTT assay. Intraperitoneal tumor responses to cisplatin and cisplatin/PDEA-PEG were evaluated in athymic mice at 4–6 weeks post-inoculation of SKOV-3 cells. PDEA-PEG nanoparticles dissolved at pH < 6, and rapidly internalized and transferred to lysosomes; it therefore was predicted that the PDEA nanoparticles would rapidly release cisplatin into cytoplasm upon integration into acidic lysosomes and thereby overwhelm the chemoresistant properties of SKOV-3 cells. Indeed, relative proportions of viable cells were diminished to a greater extent by exposure in vitro to fast-releasing nanoparticles compared to slow-releasing nanoparticles or an equivalent dose of free cisplatin. Incidences of cellular pyknosis (a morphological indicator of apoptosis) were most evident within intestinal/mesentery tumors of mice treated with cisplatin/PDEA-PEG; tumor burdens were correspondingly reduced. PMID:16529420

  17. 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

  18. Chitosan-graft-β-cyclodextrin nanoparticles as a carrier for controlled drug release.

    PubMed

    Yuan, Zeting; Ye, Yajing; Gao, Feng; Yuan, Huihui; Lan, Minbo; Lou, Kaiyan; Wang, Wei

    2013-03-25

    Chitosan (CS) grafted with β-cyclodextrin (CD-g-CS) nanoparticles as a new carrier for poorly water-soluble drugs has been developed. The CD-g-CS polymer is readily synthesized from chitosan and mono-6-deoxy-6-(p-toluenesulfonyl)-β-cyclodextrin. Three different degrees of substitution (DS) of β-cyclodextrin (β-CD) on CD-g-CS (9.6, 14.0 and 20.0%) are designed and evaluated by controlling the mole ratio of β-CD to chitosan. Then CD-g-CS nanoparticles are prepared by an ionic gelation method, with the controlled size of 202.0-589.0 nm. Stable colloidal dispersion of the nanoparticles has been formed with the zeta potential of +23.0 to +43.0 mV. In vitro stability test indicates that CD-g-CS nanoparticles are more stable in phosphate-buffered saline compared with CS nanoparticles. Finally, the poorly water-soluble drug, ketoprofen (KTP), is used as a model drug to evaluate the efficiency of the new drug delivery carrier. It is found that the encapsulation efficiency of KTP in the nanoparticles with 20% DS of CD is as high as 1.36-fold than that of CS nanoparticles. Moreover, notably KTP is released from the nanoparticles in a controlled-release manner and is pH-responsive on DS of CD. In summary, these results suggest that the CD-g-CS nanoparticles, as a general promising drug delivery system, can be used as a potential biodegradable nano-drug delivery system for controlled release of poorly water-soluble drugs with pH-responsive capability. PMID:23422276

  19. Poly(ortho ester) nanoparticle-based targeted intraocular therapy for controlled release of hydrophilic molecules.

    PubMed

    Palamoor, Mallika; Jablonski, Monica M

    2013-02-01

    Development of an efficient intraocular drug delivery nanosystem remains the most difficult challenge to attain a prolonged therapeutic effect at the site of drug action. The purpose of this work was to develop a biodegradable, long-term sustained release, and biocompatible nanoparticulate system to treat various intraocular diseases. To attain the objectives, poly(ortho ester) (POE), a hydrophobic, surface erodible, and nontoxic polymer, was selected for fabrication of nanoparticles for the first time using a double emulsion solvent evaporation method. The influence of POE molecular weight on particle size, polydispersity index, zeta potential, drug content, in vitro release, degradation, in vitro cytotoxicity, and cell uptake studies was investigated. Drug-loaded nanoparticles had a spherical shape with an average particle diameter from 241 to 298 nm and zeta potential values from -8 to -11 mV. Encapsulation efficiency ranged between 21 and 63%, depending on the type of the water-soluble molecule used. Approximately 20-30% of the loaded drug was released over a period of 14 weeks. The drug release and degradation profiles of nanoparticles followed perfect zero-order kinetics confirming the POE-surface erosion mechanism. In vitro cytotoxicity and cell uptake studies revealed the cyto-compatible nature and nonendocytic behavior of POE nanoparticles. Collectively, POE nanoparticles are a very promising vehicle for sustained delivery of therapeutics to the back of the eye. PMID:23256649

  20. Nanoparticle encapsulation and controlled release of a hydrophobic kinase inhibitor: Three stage mathematical modeling and parametric analysis.

    PubMed

    Lucero-Acuña, Armando; Guzmán, Roberto

    2015-10-15

    A mathematical model of drug release that incorporates the simultaneous contributions of initial burst, nanoparticle degradation-relaxation and diffusion was developed and used to effectively describe the release of a kinase inhibitor and anticancer drug, PHT-427. The encapsulation of this drug into PLGA nanoparticles was performed by following the single emulsion-solvent evaporation technique and the release was determined in phosphate buffer pH 7.4 at 37 °C. The size of nanoparticles was obtained in a range of 162-254 nm. The experimental release profiles showed three well defined phases: an initial fast drug release, followed by a nanoparticle degradation-relaxation slower release and then a diffusion release phase. The effects of the controlled release most relevant parameters such as drug diffusivity, initial burst constant, nanoparticle degradation-relaxation constant, and the time to achieve a maximum rate of drug release were evaluated by a parametrical analysis. The theoretical release studies were corroborated experimentally by evaluating the cytotoxicity effectiveness of the inhibitor AKT/PDK1 loaded nanoparticles over BxPC-3 pancreatic cancer cells in vitro. These studies show that the encapsulated inhibitor AKT/PDK1 in the nanoparticles is more accessible and thus more effective when compared with the drug alone, indicating their potential use in chemotherapeutic applications. PMID:26216413

  1. 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

  2. Surface functionalization of nanoparticles to control cell interactions and drug release.

    PubMed

    Luo, Rongcong; Neu, Björn; Venkatraman, Subbu S

    2012-08-20

    Nanoparticles made from poly(dl-lactide-co-glycolide) (PLGA) are used to deliver a wide range of bioactive molecules, due to their biocompatibility and biodegradability. This study investigates the surface modification of PLGA nanoparticles via the layer-by-layer (LbL) deposition of polyelectrolytes, and the effects of these coatings on the release behavior, cytotoxicity, hemolytic activity, and cellular uptake efficiency. PLGA nanoparticles are modified via LbL adsorption of two polyelectrolyte pairs: 1) poly(allylamine hydrochloride) (PAH) and poly(styrene sulfonate) (PSS) and 2) poly(L-lysine hydrobromide) (PLL) and dextran sulfate (DES). It is demonstrated that both PAH/PSS and PLL/DES coatings suppress the burst release usually observed for unmodified PLGA nanoparticles and that the release behavior can be adjusted by changing the layer numbers, layer materials, or by crosslinking the layer constituents. Neither bare nor polyelectrolyte-modified PLGA nanoparticles show any signs of cytotoxicity. However, nanoparticles with a positively charged polyelectrolyte as the outermost layer induce hemolysis, whereas uncoated particles or particles with a negatively charged polyelectrolyte as the outermost layer show no hemolytic activity. Furthermore, particles with either PAH or PLL as the outermost layer also demonstrate a higher uptake efficiency by L929 fibroblast cells, due to a higher cell-particle affinity. This study suggests that LbL coating of PLGA nanoparticles can control the release behavior of bioactive molecules as well as the surface activity, therefore providing a promising strategy to enhance the efficiency of nanoparticulate drug-delivery systems. PMID:22674655

  3. 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

  4. 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

  5. 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

  6. Efficacy of antimicrobial activity of slow release silver nanoparticles dressing in post-cardiac surgery mediastinitis.

    PubMed

    Totaro, Pasquale; Rambaldini, Manfredo

    2009-01-01

    We report our preliminary experience in post-cardiac surgery mediastinitis using a recently introduced silver-releasing dressing claiming prompt antibacterial activity. Acticoat, a silver nanoparticles slow release dressing was used in four patients with documented post-cardiac surgery mediastinitis and persistently positive microbiological cultures despite vacuum-assisted closure (VAC) therapy. In all four patients negative cultures were obtained within a maximum of 72 h and patients were discharged within a maximum of 20 days. PMID:18948308

  7. 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

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

    PubMed

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

    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

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. Real time in vitro studies of doxorubicin release from PHEMA nanoparticles

    PubMed Central

    Chouhan, Raje; Bajpai, AK

    2009-01-01

    Background Many anticancer agents have poor water solubility and therefore the development of novel delivery systems for such molecules has received significant attention. Nanocarriers show great potential in delivering therapeutic agents into the targeted organs or cells and have recently emerged as a promising approach to cancer treatments. The aim of this study was to prepare and use poly-2-hydroxyethyl methacrylate (PHEMA) nanoparticles for the controlled release of the anticancer drug doxorubicin. Results PHEMA nanoparticles have been synthesized and characterized using FTIR and scanning electron microscopy (SEM), particle size analysis and surface charge measurements. We also studied the effects of various parameters such as percent loading of drugs, chemical architecture of the nanocarriers, pH, temperature and nature of the release media on the release profiles of the drug. The chemical stability of doxorubicin in PBS was assessed at a range of pH. Conclusion Suspension polymerization of 2-hydroxyethyl methacrylate (HEMA) results in the formation of swellable nanoparticles of defined composition. PHEMA nanoparticles can potentially be used for the controlled release of the anticancer drug doxorubicin. PMID:19843333

  14. Ultrasonic atomization for spray drying: a versatile technique for the preparation of protein loaded biodegradable microspheres.

    PubMed

    Bittner, B; Kissel, T

    1999-01-01

    Bovine serum albumin (BDA) loaded microspheres with a spherical shape and smooth surface structure were successfully prepared from poly(lactide-co-glycolide) using an ultrasonic nozzle installed in a Niro laboratory spray dryer. Process and formulation parameters were investigated with respect to their influence on microsphere characteristics, such as particle size, loading capacity, and release properties. Preparation of microspheres in yields of more than 50% was achieved using an ultrasonic atomizer connected to a stream of carrier air. Microsphere characteristics could be modified by changing several technological parameters. An increased polymer concentration of the feed generated larger particles with a significantly reduced initial release of the protein. Moreover, microspheres with a smooth surface structure were obtained from the organic polymer solution with the highest viscosity. Microparticles with a low BSA loading showed a large central cavity surrounded by a thin polymer layer in scanning electron microspheres. A high protein loading led to an enlargement of the shell layer, or even to dense particles without any cavities. A continuous in vitro release pattern of BSA was obtained from the particles with low protein loading. Glass transition temperatures (Tg) of the microspheres before and after lyophilization did not differ from those of the BSA loaded particles prepared by spray drying with a rotary atomizer. Analysis of the polymer by gel permeation chromatography indicated that ultrasonication had no effect on polymer molecular weight. Molecular weight and polydispersity of the pure polymer, placebo microspheres prepared by spray drying, and placebo microspheres prepared using the ultrasonic nozzle were in the same range. In conclusion, ultrasonic atomization represents a versatile and reliable technique for the production of protein loaded biodegradable microspheres without inducing a degradation of the polymer matrix. Particle characteristics

  15. Released Plasmonic Electric Field of Ultrathin Tetrahedral-Amorphous-Carbon Films Coated Ag Nanoparticles for SERS

    PubMed Central

    Liu, Fanxin; Tang, Chaojun; Zhan, Peng; Chen, Zhuo; Ma, Hongtao; Wang, Zhenlin

    2014-01-01

    We have demonstrated the plasmonic characteristics of an ultrathin tetrahedral amorphous carbon (ta-C) film coated with Ag nanoparticles. The simulation result shows that, under resonant and non-resonant excitations, the strongest plasmonic electric field of 1 nm ta-C coated Ag nanoparticle is not trapped within the ta-C layer but is released to its outside surface, while leaving the weaker electric field inside ta-C layer. Moreover, this outside plasmonic field shows higher intensity than that of uncoated Ag nanoparticle, which is closely dependent on the excitation wavelength and size of Ag particles. These observations are supported by the SERS measurements. We expect that the ability for ultrathin ta-C coated Ag nanoparticles as the SERS substrates to detect low concentrations of target biomolecules opens the door to the applications where it can be used as a detection tool for integrated, on-chip devices. PMID:24675437

  16. 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.

  17. 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

  18. 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

  19. Encapsulation and enzyme-mediated release of molecular cargo in polysulfide nanoparticles.

    PubMed

    Allen, Brett L; Johnson, Jermaine D; Walker, Jeremy P

    2011-06-28

    Poly(propylene sulfide) nanoparticles (<150 nm) have been synthesized by an anionic, ring-opening emulsion polymerization. Upon exposure to parts per million (ppm) levels of oxidizing agent (NaOCl), hydrophobic polysulfide particles are oxidized to hydrophilic polysulfoxides and polysulfones. Utilizing this mechanism, the encapsulation of hydrophobic molecular cargo, including Nile red and Reichardt's dye, within polysulfide nanoparticles has been characterized by a variety of microscopic and spectroscopic methods and its release demonstrated via chemical oxidation. Moreover, release of cargo has been enzymatically driven by oxidoreductase enzymes such as chloroperoxidase and myeloperoxidase in the presence of low concentrations of sodium chloride (200 mM) and hydrogen peroxide (500 μM). This oxidation-driven mechanism holds promise for controlled encapsulation and release of a variety of hydrophobic cargos. PMID:21595444

  20. Stimuli-responsive releasing of gold nanoparticles and liposomes from aptamer-functionalized hydrogels

    NASA Astrophysics Data System (ADS)

    El-Hamed, Firas; Dave, Neeshma; Liu, Juewen

    2011-12-01

    Controlled release of therapeutic agents is important for improving drug efficacy and reducing toxicity. Recently, hydrogels have been used for controlled release applications. While the majority of the previous work focused on releasing the cargo in response to physical stimuli such as temperature, light, electric field, and pH, we aim to trigger cargo release in the presence of small metabolites. In our system a DNA aptamer that can bind to adenosine, AMP, and ATP was used as a linker to attach either DNA-functionalized gold nanoparticles or liposomes to DNA-functionalized hydrogels. In the presence of the metabolite, both the nanoparticle and liposome cargos were released. The effect of salt, temperature, target concentration, and drying has been systematically studied. Interestingly, we found that the gel can be completely dried while retaining the DNA linkages and adenosine induced release was still achieved after rehydration. Our work demonstrates that aptamers can be used to control the release of drugs and other materials attached to hydrogels.

  1. 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

  2. Differential magnetic catch and release: Separation, purification, and characterization of magnetic nanoparticles and particle assemblies

    NASA Astrophysics Data System (ADS)

    Beveridge, Jacob S.

    Magnetic nanoparticles uniquely combine superparamagnetic behavior with dimensions that are smaller than or the same size as molecular analytes. The integration of magnetic nanoparticles with analytical methods has opened new avenues for sensing, purification, and quantitative analysis. Applied magnetic fields can be used to control the motion and properties of magnetic nanoparticles; in analytical chemistry, use of magnetic fields provides methods for manipulating and analyzing species at the molecular level. The ability to use applied magnetic fields to control the motion and properties of magnetic nanoparticles is a tool for manipulating and analyzing species at the molecular level, and has led to applications including analyte handing, chemical sensors, and imaging techniques. This is clearly an area where significant growth and impact in separation science and analysis is expected in the future. In Chapter 1, we describe applications of magnetic nanoparticles to analyte handling, chemical sensors, and imaging techniques. Chapter 2 reports the purification and separation of magnetic nanoparticle mixtures using the technique developed in our lab called differential magnetic catch and release (DMCR). This method applies a variable magnetic flux orthogonal to the flow direction in an open tubular capillary to trap and controllably release magnetic nanoparticles. Magnetic moments of 8, 12, and 17 nm diameter CoFe2O4 nanoparticles are calculated using the applied magnetic flux density and experimentally determined force required to trap 50% of the particle sample. Balancing the relative strengths of the drag and magnetic forces enable separation and purification of magnetic CoFe2 O4 nanoparticle samples with < 20 nm diameters. Samples were characterized by transmission electron microscopy to determine the average size and size dispersity of the sample population. DMCR is further demonstrated to be useful for separation of a magnetic nanoparticle mixture, resulting

  3. 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

  4. 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.

  5. 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.

  6. Effect of porosity on the release kinetics of propafenone-loaded PEG-g-PLA nanoparticles.

    PubMed

    Sant, Shilpa; Nadeau, Véronique; Hildgen, Patrice

    2005-10-01

    Nanoparticle preparation by the emulsification-solvent evaporation method is a complex phenomenon. Various formulation factors can affect the internal structure and release of drug from nanoparticles (NPs). The aim of the present study is to optimize NPs of PEG-g-PLA polymer and study the effect of various factors on the porosity as well as release profile of drug-loaded NPs. Propafenone hydrochloride (Prop.HCl), a model drug, was encapsulated in NPs using different amounts of triethylamine (TEA) and initial drug loading levels. NPs were also prepared without TEA by using propafenone base (Prop). All the formulations were characterized for surface morphology, size and size distribution, encapsulation efficiency, thermal analysis, porosimetry and in vitro release studies. Encapsulation efficiency of Prop ranged between 10% and 43% and was dependent on initial drug loading as well as amount of TEA added. Porosity studies revealed different pore size distribution (PSD) for formulations with and without TEA. Formulations with higher drug loading showed greater volume contribution of small pores, higher fractal dimension suggesting more complex pore structure and slower drug release, probably due to decrease in the effective diffusion coefficient of Prop. Results suggest that formulation factors play an important role affecting the porosity and release rate of NPs. Also, fractal dimension could be one of the most important factors in determining the release behavior of NPs. PMID:16099525

  7. 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

  8. 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.

  9. 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

  10. 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

  11. 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. PMID:26848012

  12. Release Activation of Iron Oxide Nanoparticles (REACTION): A novel environmentally sensitive MRI paradigm

    PubMed Central

    Granot, Dorit; Shapiro, Erik M.

    2011-01-01

    Smart contrast agents for MRI-based cell tracking would enable the use of MRI methodologies to not only detect the location of cells, but also gene expression. Here we report on a new enzyme/contrast agent paradigm which involves the enzymatic degradation of the polymer coating of magnetic nanoparticles to release encapsulated magnetic cores. Cells were labeled with particles coated with a polymer which is cleavable by a specific enzyme. This coat restricts the approach of water to the particle, preventing the magnetic core from efficiently relaxing protons. The reactive enzyme was delivered to cells and changes in cellular T2 and T2* relaxation times of ~ 35% and ~ 50% were achieved in vitro. Large enhancements of dark contrast volume (240%) and CNR (48%) within the contrast regions were measured, in vivo, for cells co-labeled with enzyme and particles. These results warrant exploration of genetic avenues towards achieving RElease ACTivation of Iron Oxide Nanoparticles (REACTION). PMID:21360745

  13. Controlled Embedding of Metal Oxide Nanoparticles in ZSM-5 Zeolites through Preencapsulation and Timed Release.

    PubMed

    Lai, Yungchieh; Rutigliano, Michael N; Veser, Götz

    2015-09-29

    We report a straightforward and transferrable synthesis strategy to encapsulate metal oxide nanoparticles (NPs) in mesoporous ZSM-5 via the encapsulation of NPs into silica followed by conversion of the NP@silica precursor to NP@ZSM-5. The systematic bottom-up approach allows for straightforward, precise control of both the metal weight loading and size of the embedded NP and yields uniform NP@ZSM-5 microspheres composed of stacked ZSM-5 nanorods with substantial mesoporosity. Key to the synthesis is the timed release of the embedded NPs during dissolution of the silica matrix in the hydrothermal conversion step, which finely balances the rate of NP release with the rate of SiO2 dissolution and the subsequent nucleation of aluminosilicate. The synthesis approach is demonstrated for Zn, Fe, and Ni oxide encapsulation in ZSM-5 but can be expected to be broadly transferrable for the encapsulation of metal and metal oxide nanoparticles into other zeolite structures. PMID:26352788

  14. 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. PMID:26036966

  15. 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

  16. 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. PMID:23542495

  17. 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

  18. 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. PMID:26378248

  19. Effect of drug release kinetics on nanoparticle therapeutic efficacy and toxicity.

    PubMed

    Sethi, Manish; Sukumar, Rohit; Karve, Shrirang; Werner, Michael E; Wang, Edina C; Moore, Dominic T; Kowalczyk, Sonya R; Zhang, Liangfang; Wang, Andrew Z

    2014-02-21

    The effects of nanoparticle (NP) properties, such as size, shape and surface charge, on their efficacy and toxicity have been studied extensively. However, the effect of controlled drug release on NP efficacy and toxicity has not been thoroughly evaluated in vivo. Our study aims to fill this knowledge gap. A key challenge in characterizing the relationship between drug release and therapeutic ratio is to fabricate NPs that differ only in their drug release profile but are otherwise identical. To overcome this challenge, we developed crosslinkable lipid shell (CLS) NPs, where the drug release kinetics can be modulated without changing any other NP property. Using CLS NPs with wortmannin and docetaxel as model drugs, we determined the relationship between the release kinetics and therapeutic efficacy and toxicity of the drugs. We have determined that drug release kinetics can affect the therapeutic efficacy of NP docetaxel and NP wortmannin in vitro and in vivo. Our study also demonstrates that a decrease in drug release kinetics can result in a decrease in the hepatotoxicity of CLS NP wortmannin. Using two model drugs, the current findings provide the first direct evidence that NP drug release profile is a critical factor in determining the NP therapeutics' efficacy and toxicity in vivo. PMID:24418914

  20. Effect of drying and loading methods on the release behavior of ciprofloxacin from starch nanoparticles.

    PubMed

    Shi, Aimin; Li, Dong; Liu, Hongzhi; Adhikari, Benu; Wang, Qiang

    2016-06-01

    Drug loading into and release from starch nanoparticles (StNPs), one kind of novel biological macromolecule, were investigated. Two drying methods (spray and vacuum freeze drying) and drug loading methods (coating and adsorption) were used for evaluation. 40% (w/w) of ciprofloxacin was loaded using coating method while only 7% for adsorption method. Glass transition temperature (Tg) and melting point temperature (Tmp) of ciprofloxacin loaded starch nanoparticles varied from 40°C to 55°C and 125°C to 175°C. Particles using adsorption method had lower loading rate of ciprofloxacin, higher Tg, Tmp and release rate compared to using coating method. Tg and Tmp were not affected by these two drying methods. Release rate of ciprofloxacin was higher from freeze dried particles than from spray dried particles using coating method. For adsorption method, drying methods had not effect on the release rate. A double decay exponential model was able to fit the release data suitably well with coefficient of determination (R(2))>0.97. PMID:26893049

  1. Charge dependence of ligand release and monolayer stability of gold nanoparticles by biogenic thiols.

    PubMed

    Chompoosor, Apiwat; Han, Gang; Rotello, Vincent M

    2008-07-01

    The effect of surface charge on the stability of gold nanoparticles (AuNPs) to the biogenic thiols glutathione (GSH), dihydrolipoic acid (DHLA), and cysteine was quantified. It was observed that the rate of release of fluorescein-tagged ligand was determined by the surface charge of the AuNPs, with cationic particles much more labile than anionic analogues. This ability to tune stability is significant for the design of both delivery vehicles and intracellular probes. PMID:18553895

  2. 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

  3. 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

  4. Model of controlled drug release from functionalized magnetic nanoparticles by a nonheating alternating-current magnetic field

    NASA Astrophysics Data System (ADS)

    Golovin, Yu. I.; Klyachko, N. L.; Gribanovskii, S. L.; Golovin, D. Yu.; Majouga, A. G.

    2016-03-01

    A magnetohydrodynamic model of controlled drug macromolecule release from transport magnetic nanoparticles covered by a polymer shell under the influence of a low-frequency (<1 kHz) nonheating magnetic field is described.

  5. 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

  6. Release kinetics of an amphiphilic photosensitizer by block-polymer nanoparticles.

    PubMed

    Kerdous, Rachid; Sureau, Franck; Bour, Aurélien; Bonneau, Stéphanie

    2015-11-30

    Block-polymer nanoparticles are now well-known candidates for the delivery of various non-soluble drugs to cells. The release of drugs from these nanoparticles is a major concern related to their efficiency as nanovectors and is still not completely deciphered. Various processes have been identified, depending of both the nature of the block-polymer and those of the drugs used. We focused our interest on an amphiphilic photosensitizer studied for photodynamic treatments of cancer, Pheophorbide-a (Pheo). We studied the transfer of Pheo from poly(ethyleneglycol-b-ϵ-caprolactone) nanoparticles (I) to MCF-7 cancer cells and (II) to models of membranes. Altogether, our results suggest that the delivery of the major part of the Pheo by the nanoparticles occurs via a direct transfer of Pheo from the nanoparticles to the membrane, by collision. A minor process may involve the internalization of a small amount of the nanoplatforms by the cells. So, this research illustrates the great care necessary to address the question of the choice of such nanocarriers, in relation with the properties - in particular the relative hydrophobicity - of the drugs encapsulated, and gives elements to predict the mechanism and the efficiency of the delivery. PMID:26387620

  7. Pharmaceutical suspension containing both immediate/sustained-release amoxicillin-loaded gelatin nanoparticles: preparation and in vitro characterization.

    PubMed

    Harsha, Sree

    2013-01-01

    Pharmaceutical suspension containing oral dosage forms delivering both immediate-release and sustained-release amoxicillin was developed as a new dosage form to eradicate Helicobacter pylori. Amoxicillin-loaded gelatin nanoparticles are able to bind with the mucosal membrane after delivery to the stomach and could escalate the effectiveness of a drug, providing dual release. The objective of this study was to develop amoxicillin nanoparticles using innovative new technology--the Büchi Nano Spray Dryer B-90 - and investigate such features as drug content, particle morphology, yield, in vitro release, flow properties, and stability. The nanoparticles had an average particle size of 571 nm. The drug content and percentage yield was 89.2% ± 0.5% and 93.3% ± 0.6%, respectively. Angle of repose of nanoparticle suspension was 26.3° and bulk density was 0.59 g/cm(3). In vitro drug release of formulations was best fitted by first-order and Peppas models with R (2) of 0.9841 and 0.9837 respectively; release profile was 15.9%, while; for the original drug, amoxicillin, under the same conditions, 90% was released in the first 30 minutes. The nanoparticles used in this study enabled sustained release of amoxicillin over an extended period of time, up to 12 hours, and were stable for 12 months under accelerated storage conditions of 25 °C ± 2 °C and 60% ± 5% relative humidity. PMID:24101859

  8. In Vitro Release Kinetics of Antituberculosis Drugs from Nanoparticles Assessed Using a Modified Dissolution Apparatus

    PubMed Central

    Gao, Yuan; Zuo, Jieyu; Bou-Chacra, Nadia; Pinto, Terezinha de Jesus Andreoli; Clas, Sophie-Dorothee; Walker, Roderick B.; Löbenberg, Raimar

    2013-01-01

    The aim of this study was to assess the in vitro release kinetics of antituberculosis drug-loaded nanoparticles (NPs) using a “modified” cylindrical apparatus fitted with a regenerated cellulose membrane attached to a standard dissolution apparatus (modifiedcylinder method). The model drugs that were used were rifampicin (RIF) and moxifloxacin hydrochloride (MX). Gelatin and polybutyl cyanoacrylate (PBCA) NPs were evaluated as the nanocarriers, respectively. The dissolution and release kinetics of the drugs from loaded NPs were studied in different media using the modified cylinder method and dialysis bag technique was used as the control technique. The results showed that use of the modified cylinder method resulted in different release profiles associated with unique release mechanisms for the nanocarrier systems investigated. The modified cylinder method also permitted discrimination between forced and normal in vitro release of the model drugs from gelatin NPs in the presence or absence of enzymatic degradation. The use of dialysis bag technique resulted in an inability to differentiate between the mechanisms of drug release from the NPs in these cases. This approach offers an effective tool to investigate in vitro release of RIF and MX from NPs, which further indicate that this technique can be used for performance testing of nanosized carrier systems. PMID:23936771

  9. 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

  10. Inherently antioxidant and antimicrobial tannic acid release from poly(tannic acid) nanoparticles with controllable degradability.

    PubMed

    Sahiner, Nurettin; Sagbas, Selin; Aktas, Nahit; Silan, Coskun

    2016-06-01

    From a natural polyphenol, Tannic acid (TA), poly(TA) nanoparticles were readily prepared using a single step approach with three different biocompatible crosslinkers; trimethylolpropane triglycidyl ether (TMPGDE), poly(ethylene glycol) diglycidyl ether (PEGGE), and trisodium trimetaphosphate (STMP). P(TA) particles were obtained with controllable diameters between 400 to 800nm with -25mV surface charge. The effect of synthesis conditions, such as the emulsion medium, pH values of TA solution, and the type of crosslinker, on the shape, size, dispersity, yield, and degradability of poly(Tannic Acid) (p(TA)) nanoparticles was systematically investigated. The hydrolytic degradation amount in physiological pH conditions of 5.4, 7.4, and 9.0 at 37.5°C were found to be in the order TMPGDEnanoparticles can be controlled by the appropriate choice of crosslinker, and the pH of releasing media. The highest TA release, 600mg/g, was obtained for TMPGDE-crosslinked p(TA) particles in intestinal pH conditions (pH 9) over 3 days; whereas, a slow and linear TA release profile over almost 30 days was obtained by using PEGGE-crosslinked p(TA) in body fluid pH conditions (pH 7.4). The total phenol content of p(TA) particles was calculated as 70±1μgmL(-1) for 170μgmL(-1) p(TA), and the trolox equivalent antioxidant capacity was found to be 2027±104mM trolox equivalent g(-1). Moreover, p(TA) nanoparticles demonstrated strong antimicrobial effects against common bacterial strains. More interestingly, with a higher concentration of p(TA) particles, higher blood clotting indices were obtained. PMID:26970821

  11. Chain and pore-blocking effects on matrix degradation in protein-loaded microgels.

    PubMed

    Widenbring, Ronja; Frenning, Göran; Malmsten, Martin

    2014-10-13

    Factors affecting matrix degradation in protein-loaded microgels were investigated for dextran-based microgels, the sugar-binding protein Concanavalin A (ConA), and the dextran-degrading enzyme Dextranase. For this system, effects of enzyme, protein, and glucose concentrations, as well as pH, were considered. Microgel network degradation was monitored by micromanipulator-assisted light microscopy, whereas enzyme and protein distributions were monitored by confocal microscopy. Results show that Dextranase-mediated microgel degradation increased with increasing enzyme concentration, whereas an increased ConA loading in the dextran microgels caused a concentration-dependent decrease in microgel degradation. In the presence of glucose, competitive release of microgel-bound ConA restored the microgel degradation observed in the absence of ConA. To clarify effects of mass transport limitations, microgel degradation was compared to that of non-cross-linked dextran, demonstrating that ConA limits enzyme substrate access in dextran microgels primarily through pore blocking and induction of pore shrinkage. The experimentally observed effects were qualitatively captured by a modified Michaelis-Menten approach for spherical symmetry, in which network blocking by ConA was included. Taken together, the results demonstrate that matrix degradation of protein-loaded microgels depends sensitively on a number of factors, which need to be considered in the use of microgels in biomedical applications. PMID:25144139

  12. 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

  13. 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.

  14. Nitric oxide-releasing nanoparticles accelerate wound healing by promoting fibroblast migration and collagen deposition.

    PubMed

    Han, George; Nguyen, Long N; Macherla, Chitralekha; Chi, Yuling; Friedman, Joel M; Nosanchuk, Joshua D; Martinez, Luis R

    2012-04-01

    Wound healing is a complex process that involves coordinated interactions between diverse immunological and biological systems. Long-term wounds remain a challenging clinical problem, affecting approximately 6 million patients per year, with a high economic impact. To exacerbate the problem, these wounds render the individual susceptible to life-threatening microbial infections. Because current therapeutic strategies have proved suboptimal, it is imperative to focus on new therapeutic approaches and the development of technologies for both short- and long-term wound management. In recent years, nitric oxide (NO) has emerged as a critical molecule in wound healing, with NO levels increasing rapidly after skin damage and gradually decreasing as the healing process progresses. In this study, we examined the effects of a novel NO-releasing nanoparticle technology on wound healing in mice. The results show that the NO nanoparticles (NO-np) significantly accelerated wound healing. NO-np modified leukocyte migration and increased tumor growth factor-β production in the wound area, which subsequently promoted angiogenesis to enhance the healing process. By using human dermal fibroblasts, we demonstrate that NO-np increased fibroblast migration and collagen deposition in wounded tissue. Together, these data show that NO-releasing nanoparticles have the ability to modulate and accelerate wound healing in a pleiotropic manner. PMID:22306734

  15. Cell penetrating peptides released from thermosensitive nanoparticles suppress proinflammatory cytokine response by specifically targeting inflamed cartilage explants

    PubMed Central

    Panitch, Alyssa

    2014-01-01

    Cell penetrating anti-inflammatory peptide KAFAKLAARLYRKALARQLGVAA (KAFAK) has the ability to suppress pro-inflammatory cytokines TNF-α and IL-6 when released from degradable and non-degradable Poly(NIPAm-AMPS) nanoparticles. In vitro human macrophage model with THP1 human monocytes and ex vivo bovine knee cartilage tissue both showed a dose dependent suppression of pro-inflammatory cytokines when treated with KAFAK loaded poly(NIPAm-AMPS) nanoparticles. When bovine knee cartilage explants were treated with KAFAK loaded poly(NIPAm-AMPS) nanoparticles, rapid and highly selective targeting of only damaged tissue occurred. This study has demonstrated selective targeting and therapeutic efficacy of KAFAK when released from both degradable and non degradable poly(NIPAm-AMPS) nanoparticles in in vitro and ex vivo models. As a result, poly(NIPAm-AMPS) nanoparticles loaded with KAFAK could a very effective tool to treat osteoarthritis. PMID:23041412

  16. 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

  17. 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...

  18. Magnetic Assembly and Cross-Linking of Nanoparticles for Releasable Magnetic Microstructures.

    PubMed

    Velez, Camilo; Torres-Díaz, Isaac; Maldonado-Camargo, Lorena; Rinaldi, Carlos; Arnold, David P

    2015-10-27

    This article describes a versatile method to fabricate magnetic microstructures with complex two-dimensional geometric shapes using magnetically assembled iron oxide (Fe3O4) and cobalt ferrite (CoFe2O4) nanoparticles. Magnetic pole patterns are imprinted into magnetizable media, onto which magnetic nanoparticles are assembled from a colloidal suspension into defined shapes via the shaped magnetic field gradients. The kinetics of this assembly process are studied by evaluation of the microstructure features (e.g., line width and height) as a function of time, particle type, and volume fraction. After assembly, the iron oxide particles are cross-linked in situ and subsequently released by dissolving a sacrificial layer. The free-floating magnetic structures are shown to retain their patterned shape during manipulation with external magnetic fields. PMID:26364509

  19. Nanotechnology in oncology: Characterization and in vitro release kinetics of cisplatin-loaded albumin nanoparticles: Implications in anticancer drug delivery

    PubMed Central

    Das, Saikat; Jagan, Lavanya; Isiah, Rajesh; Rajesh, B.; Backianathan, Selvamani; Subhashini, J.

    2011-01-01

    Context: Nanotechnology is an empowering technology that holds promise in cancer therapeutics by increasing the ratio of tumor control probability to normal tissue complication probability. It can increase the bioavailability of the drug at the target site, reduce the frequency of administration and reach otherwise lesser-accessible sites. The present study shows the feasibility of the cisplatin-loaded albumin nanoparticle as a sustained delivery system. Aims: Cisplatin is one of the most widely used chemotherapeutic agents for the treatment of malignant disorders. Conventional cisplatin formulation given as intravenous infusion has low bioavailability to the target organ in addition to significant side-effects, like ototoxicity and nephrotoxicity. The aim of this study was to develop a protein-based nanoparticulate system for sustained release of cisplatin. Materials and Methods: Nanoparticles were prepared by the coacervaton method of microcapsulation and chemical cross-linking with glutaraldehyde. Particle size was characterized by dynamic light scattering and transmission electron microscopy. Results and Conclusions: Using the coacervation method, nanoparticles of less than 70 nm diameter were produced. Drug encapsulation measured by ultraviolet spectroscopy varied from 30% to 80% for different ratios of cisplatin and protein. In vitro release kinetics shows that the nanoparticle-based formulation has biphasic release kinetics and is capable of sustained release compared with the free drug (80% release in 45 h). The study proves the feasibility of the albumin-based cisplatin nanoparticle formulation as a sustained release vehicle of cisplatin. PMID:21844995

  20. Effect of drug release kinetics on nanoparticle therapeutic efficacy and toxicity

    NASA Astrophysics Data System (ADS)

    Sethi, Manish; Sukumar, Rohit; Karve, Shrirang; Werner, Michael E.; Wang, Edina C.; Moore, Dominic T.; Kowalczyk, Sonya R.; Zhang, Liangfang; Wang, Andrew Z.

    2014-01-01

    The effects of nanoparticle (NP) properties, such as size, shape and surface charge, on their efficacy and toxicity have been studied extensively. However, the effect of controlled drug release on NP efficacy and toxicity has not been thoroughly evaluated in vivo. Our study aims to fill this knowledge gap. A key challenge in characterizing the relationship between drug release and therapeutic ratio is to fabricate NPs that differ only in their drug release profile but are otherwise identical. To overcome this challenge, we developed crosslinkable lipid shell (CLS) NPs, where the drug release kinetics can be modulated without changing any other NP property. Using CLS NPs with wortmannin and docetaxel as model drugs, we determined the relationship between the release kinetics and therapeutic efficacy and toxicity of the drugs. We have determined that drug release kinetics can affect the therapeutic efficacy of NP docetaxel and NP wortmannin in vitro and in vivo. Our study also demonstrates that a decrease in drug release kinetics can result in a decrease in the hepatotoxicity of CLS NP wortmannin. Using two model drugs, the current findings provide the first direct evidence that NP drug release profile is a critical factor in determining the NP therapeutics' efficacy and toxicity in vivo.The effects of nanoparticle (NP) properties, such as size, shape and surface charge, on their efficacy and toxicity have been studied extensively. However, the effect of controlled drug release on NP efficacy and toxicity has not been thoroughly evaluated in vivo. Our study aims to fill this knowledge gap. A key challenge in characterizing the relationship between drug release and therapeutic ratio is to fabricate NPs that differ only in their drug release profile but are otherwise identical. To overcome this challenge, we developed crosslinkable lipid shell (CLS) NPs, where the drug release kinetics can be modulated without changing any other NP property. Using CLS NPs with

  1. 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

  2. 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.

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

    PubMed

    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

  4. Synthesis of water dispersed nanoparticles from different polysaccharides and their application in drug release.

    PubMed

    Ayadi, Farouk; Bayer, Ilker S; Marras, Sergio; Athanassiou, Athanassia

    2016-01-20

    This work describes an original method to synthesize nanoparticles of starch (NPS), cellulose (NPC), and cellulose/hemicellulose (NPCH) from corn starch (S), microcrystalline cellulose (MCC) and hemp fibers (H), respectively. The synthesis is simply based on the treatment of the latter with trifluoroacetic acid. The resultant nanoparticles are easily dispersed in aqueous solutions. The size of these quasi-spherical particles, as measured by TEM and AFM, is less than 10nm. Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction analysis (XRD) of NPC revealed the loss of original cellulose crystallinity and formation of cellulose II structure after dispersion in water, while the structures of NPCH and NPS were found to be amorphous. Thermogravimetric analysis (TGA) results indicated that the resultant NPC and NPS undergo a two-step pyrolysis, whereas the unprocessed MCC and S undergo one-step pyrolysis. Curcumin was chosen as a model drug. As a model drug release system, NPS were found to release curcumin in a controlled way through a pH-dependent mechanism, with release capacity of about 43% and 65% of the original loaded curcumin under pH 7.4 and 1.2, respectively. PMID:26572357

  5. Granulometric characterization of airborne particulate release during spray application of nanoparticle-doped coatings.

    PubMed

    Göhler, Daniel; Stintz, Michael

    2014-01-01

    Airborne particle release during the spray application of coatings was analyzed in the nanometre and micrometre size range. In order to represent realistic conditions of domestic and handcraft use, the spray application was performed using two types of commercial propellant spray cans and a manual gravity spray gun. Four different types of coatings doped with three kinds of metal-oxide tracer nanoparticle additives (TNPA) were analyzed. Depending on the used coating and the kind of spray unit, particulate release numbers between 5 × 10(8) and 3 × 10(10) particles per gram ejection mass were determined in the dried spray aerosols. The nanoparticulate fraction amounted values between 10 and 60 no%. The comparison between nanoparticle-doped coatings with non-doped ones showed no TNPA-attributed differences in both the macroscopic spray process characteristics and the particle release numbers. SEM, TEM and EDX-analyzes showed that the spray aerosols were composed of particles made up solely from matrix material and sheathed pigments, fillers and TNPAs. Isolated ZnO- or Fe2O3-TNPAs could not be observed. PMID:25152690

  6. 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

  7. Enzyme-responsive doxorubicin release from dendrimer nanoparticles for anticancer drug delivery

    PubMed Central

    Lee, Sang Joon; Jeong, Young-Il; Park, Hyung-Kyu; Kang, Dae Hwan; Oh, Jong-Suk; Lee, Sam-Gyu; Lee, Hyun Chul

    2015-01-01

    Background Since cancer cells are normally over-expressed cathepsin B, we synthesized dendrimer-methoxy poly(ethylene glycol) (MPEG)-doxorubicin (DOX) conjugates using a cathepsin B-cleavable peptide for anticancer drug targeting. Methods Gly-Phe-Leu-Gly peptide was conjugated with the carboxylic acid end groups of a dendrimer, which was then conjugated with MPEG amine and doxorubicin by aid of carbodiimide chemistry (abbreviated as DendGDP). Dendrimer-MPEG-DOX conjugates without Gly-Phe-Leu-Gly peptide linkage was also synthesized for comparison (DendDP). Nanoparticles were then prepared using a dialysis procedure. Results The synthesized DendGDP was confirmed with 1H nuclear magnetic resonance spectroscopy. The DendDP and DendGDP nanoparticles had a small particle size of less than 200 nm and had a spherical morphology. DendGDP had cathepsin B-sensitive drug release properties while DendDP did not show cathepsin B sensitivity. Further, DendGDP had improved anticancer activity when compared with doxorubicin or DendDP in an in vivo CT26 tumor xenograft model, ie, the volume of the CT26 tumor xenograft was significantly inhibited when compared with xenografts treated with doxorubicin or DendDP nanoparticles. The DendGDP nanoparticles were found to be relatively concentrated in the tumor tissue and revealed stronger fluorescence intensity than at other body sites while doxorubicin and DendDP nanoparticles showed strong fluorescence intensity in the various organs, indicating that DendGDP has cathepsin B sensitivity. Conclusion DendGDP is sensitive to cathepsin B in tumor cells and can be used as a cathepsin B-responsive drug targeting strategy. We suggest that DendGDP is a promising vehicle for cancer cell targeting. PMID:26357473

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

    PubMed

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

    2016-03-28

    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. PMID:26952741

  9. 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. PMID:21589964

  10. 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

  11. 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

    2015-01-01

    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. 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

  12. 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

  13. 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. PMID:27146359

  14. 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.

  15. 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

  16. 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

  17. 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

  18. 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

  19. Utilizing Chemo-mechanically Functionalized Oscillating Fins to ``Catch and Release'' Nanoparticles in Binary Flow

    NASA Astrophysics Data System (ADS)

    Liu, Ya; Kuksenok, Olga; Bhattacharya, Amitabh; Ma, Yongting; He, Ximin; Aizenberg4, Joanna; Balazs, Anna

    2014-03-01

    In biomimetics, designing an effective ``catch and release'' device for the selective removal of target species from the surrounding solution is critical for developing autonomous sensors and sorters. Using computer simulations, we model an array of oscillating fins that are tethered on the floor of a microchannel and immersed in a mixture of binary fluid stream and binary nanoparticles. During the oscillation, the fins with the specific chemical wetting reach the upper fluid when they are upright and are entirely immersed within the lower stream when they are tilted. We introduce specific interaction between the fins and particulates in the solution and determine conditions where the oscillating fins can selectively ?catch? target nanoparticles within the upper fluid stream and then release these particles into the lower stream. We isolate the effects of wetting contact angle between fins and fluid and the mode of fins' oscillations that lead to the efficient extraction of target species from the upper stream and their placement into the lower fluid. These studies provide fundamental insights into the system's complex dynamics and mechanism for detection, separation, and purification of multi-component mixtures.

  20. 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. PMID:24880680

  1. 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. PMID:26377025

  2. 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

  3. Biphasic release of gentamicin from chitosan/fucoidan nanoparticles for pulmonary delivery.

    PubMed

    Huang, Yi-Cheng; Li, Rou-Ying; Chen, Jiun-Yu; Chen, Jen-Kun

    2016-03-15

    Gentamicin (GM), one of the most commonly used aminoglycoside antibiotics, has been used for treating pneumonia; however, the applicability of GM is limited by its bioavailability and toxic side effects. This study used chitosan (CS)/fucoidan (F) nanoparticles (NPs) to develop a nanoformulation for pulmonary delivery of GM, presenting a biphasic release feature. The NPs exhibited a zero-order release of GM for the first 10h, followed by a sustained release of up to 72h, attaining a value of 99%. The GM-loaded CS/F NPs provide multiple antimicrobial capabilities against Klebsiella pneumoniae, including the CS and biphasic release of GM. Compared with the intravenous administration of free GM (0.5mg/kg), the intratracheal administration of GM-loaded CS/F NP (0.27mg/kg) presented a superior area under the concentration-time curve/minimum inhibitory concentration ratio, indicating the simultaneous improvement of antimicrobial efficacy and elimination of systemic toxicity. These results suggested that CS/F NPs are potential carriers in pulmonary delivery of GM for pneumonia treatment. PMID:26794744

  4. Optimizing indomethacin-loaded chitosan nanoparticle size, encapsulation, and release using Box-Behnken experimental design.

    PubMed

    Abul Kalam, Mohd; Khan, Abdul Arif; Khan, Shahanavaj; Almalik, Abdulaziz; Alshamsan, Aws

    2016-06-01

    Indomethacin chitosan nanoparticles (NPs) were developed by ionotropic gelation and optimized by concentrations of chitosan and tripolyphosphate (TPP) and stirring time by 3-factor 3-level Box-Behnken experimental design. Optimal concentration of chitosan (A) and TPP (B) were found 0.6mg/mL and 0.4mg/mL with 120min stirring time (C), with applied constraints of minimizing particle size (R1) and maximizing encapsulation efficiency (R2) and drug release (R3). Based on obtained 3D response surface plots, factors A, B and C were found to give synergistic effect on R1, while factor A has a negative impact on R2 and R3. Interaction of AB was negative on R1 and R2 but positive on R3. The factor AC was having synergistic effect on R1 and on R3, while the same combination had a negative effect on R2. The interaction BC was positive on the all responses. NPs were found in the size range of 321-675nm with zeta potentials (+25 to +32mV) after 6 months storage. Encapsulation, drug release, and content were in the range of 56-79%, 48-73% and 98-99%, respectively. In vitro drug release data were fitted in different kinetic models and pattern of drug release followed Higuchi-matrix type. PMID:26893052

  5. Stimulus-responsive Controlled Release System by Covalent Immobilization of an Enzyme into Mesoporous Silica Nanoparticles

    PubMed Central

    Méndez, Jessica; Monteagudo, Alina; Griebenow, Kai

    2012-01-01

    Mesoporous silica nanoparticles (MSN) have emerged as an attractive class of drug delivery carriers for therapeutic agents. Herein, we explored the covalent immobilization of proteins into MSN to generate a stimulus-responsive controlled release system. First, MSN were functionalized with thiol groups using (mercaptopropyl)-trimethoxysilane (MPTMS). Functionalization was verified by X-ray photoelectron spectroscopy (XP), Fourier-transform infrared (FTIR) spectroscopy, and dynamic light scattering. The model enzyme carbonic anhydrase (CA) was coupled to sulfosuccinimidyl 6-[3'(2-pyridyldithio)-propionamido]hexanoate (Sulfo-LC-SPDP) at a low ratio of 1:1 to prevent enzyme inactivation and subsequently covalently immobilized into MSN via thiol-disulfide interchange. The enzyme could be released from MSN with 10 mM glutathione which represents intra-cellular redox conditions while it remained bound to the MSN at extra-cellular redox conditions represented by 1 μM glutathione. The activity of the released enzyme was >80% demonstrating that the enzyme was still largely functional and active after immobilization and release. Human cervical cancer (HeLa) cells were incubated with the MSN-CA bioconjugates at various concentrations for 24 h and the data show good biocompatibility. In summary, we demonstrate the potential of MSN as potential drug delivery systems for proteins. PMID:22375899

  6. 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. PMID:27128362

  7. Sustained release of PTX-incorporated nanoparticles synergized by burst release of DOX⋅HCl from thermosensitive modified PEG/PCL hydrogel to improve anti-tumor efficiency.

    PubMed

    Xu, Shuxin; Wang, Weiwei; Li, Xijing; Liu, Jianping; Dong, Anjie; Deng, Liandong

    2014-10-01

    As drug therapies become increasingly sophisticated, the synergistic benefits of two or more drugs are often required. In this study, we aimed at improving anti-tumor efficiency of paclitaxel (PTX)-incorporated thermo-sensitive injectable hydrogel by the synergy of burst release of doxorubicin hydrochloride (DOX⋅HCl). Thermosensitive injectable hydrogel composed of nanoparticles assembled from amphiphilic copolymer poly(ε-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone)-poly(ethylene glycol)-poly(ε-caprolaone-co-1,4,8-trioxa[4.6]spiro-9-undecanone) (PECT) was fabricated. Hydrophobic PTX and hydrophilic DOX⋅HCl were loaded simultaneously in the thermo-sensitive injectable hydrogel by a two-stage entrapment. Thermosensitive gelling behaviors of drug-loading PECT nanoparticle aqueous dispersions were studied. In vitro release profiles of PTX and DOX⋅HCl and in vivo anti-tumor effect by dual drugs from PECT hydrogel were investigated. The results showed that hydrophilic and hydrophobic drugs could be successfully entrapped in PECT hydrogel simultaneously without affecting its thermo-sensitive behavior. In vitro release profiles demonstrated the burst release of DOX⋅HCl and the sustained release of PTX. Anti-tumor effect was improved by a fast and tense attack caused by the burst release of hydrophilic DOX⋅HCl from hydrogel, which was continued by the sequent sustained release of PTX-incorporated nanoparticles and remnant DOX⋅HCl. Unintentionally, entrapped in PECT hydrogel, hydrophilic DOX⋅HCl was observed to have a sustained releasing pattern in vitro and in vivo. PMID:24931190

  8. 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

  9. 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

  10. Potential application of functional porous TiO2 nanoparticles in light-controlled drug release and targeted drug delivery.

    PubMed

    Wang, Tianyi; Jiang, Haitao; Wan, Long; Zhao, Qinfu; Jiang, Tongying; Wang, Bing; Wang, Siling

    2015-02-01

    Novel multifunctional porous titanium dioxide (TiO2) nanoparticles modified with polyethylenimine (PEI) were developed to explore the feasibility of exploiting the photocatalytic property of titanium dioxide to achieve ultraviolet (UV) light triggered drug release. Additionally, in order to further realize targeting delivery, folic acid, which chemically conjugated to the surface of the functionalized multifunctional porous TiO2 nanoparticles through amide linkage with free amine groups of PEI, was used as a cancer-targeting agent to effectively promote cancer-cell-specific uptake through receptor-mediated endocytosis. And a typical poorly water-soluble anti-cancer drug, paclitaxel, was encapsulated in multifunctional porous TiO2 nanoparticles. The PEI on the surface of multifunctional porous TiO2 nanoparticles could effectively block the channel to prevent premature drug release, thus providing enough circulation time to target cancer cells. Following UV light radiation, PEI molecules on the surface were cut off by the free radicals (OH˙ and O2-) that TiO2 produced, and then the drug loaded in the carrier was released rapidly into the cytoplasm. Importantly, the amount of drug released from multifunctional porous TiO2 nanoparticles can be regulated by the UV-light radiation time to further control the anti-cancer effect. This multifunctional porous TiO2 nanoparticle exhibits a combination of stimuli-triggered drug release and cancer cell targeting. The authors believe that the present study will provide important information for the use of porous TiO2 nanomaterials in light-controlled drug release and targeted therapy. PMID:25462846

  11. 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

  12. 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. PMID:24985790

  13. Doxorubicin loading, release, and stability of polyamidoamine dendrimer-coated magnetic nanoparticles.

    PubMed

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

    2013-06-01

    Nanotechnology is a promising alternative to overcome the limitations of classical chemotherapy. As a novel approach, dendrimer-coated magnetic nanoparticles (DcMNPs) maintain suitable drug delivery system because of their buildup of functional groups, symmetry perfection, nanosize, and internal cavities. They can also be targeted to the tumor site in a magnetic field. The aim of this study is to obtain an effective targeted delivery system for doxorubicin, using polyamidoamine (PAMAM) DcMNPs. Different generations (G2 , G3 , G4 , and G7 ) of PAMAM DcMNPs were synthesized. Doxorubicin loading, release, and stability efficiencies in these nanoparticles (NPs) were studied. The results showed that low-generation NPs obtained in this study have pH-sensitive drug release characteristics. G4 DcMNP, which releases most of the drug in lower pH, seems to be the most suitable generation for efficient Doxorubicin delivery. Furthermore, application of doxorubicin-loaded G4 DcMNPs may help to overcome doxorubicin resistance in MCF-7 cells. On the contrary, G2 and G3 DcMNPs would be suitable for the delivery of drugs such as vinca alkaloids (Johnson IS, Armstrong JG, Gorman M, Burnett JP. 1963. Cancer Res 23:1390-1427.) and taxenes (Clarke SJ, Rivory LP. 1999. Clin Pharmacokinet 36(2):99-114.), which show their effects in cytoplasm. The results of this study can provide new insights in the development of pH-sensitive targeted drug delivery systems to overcome drug resistance during cancer therapy. PMID:23558592

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

    PubMed

    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. PMID:26088998

  15. 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.

  16. 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

  17. Versatile FRET-Based Mesoporous Silica Nanoparticles for Real-Time Monitoring of Drug Release

    PubMed Central

    Lai, Jinping; Shah, Birju P.; Garfunkel, Eric; Lee, Ki-Bum

    2013-01-01

    We describe the development of a versatile fluorescence resonance energy transfer (FRET)-based real-time monitoring system, consisting of (a) coumarin-labeled-cysteine tethered mesoporous silica nanoparticles (MSNs) as the drug carrier, (b) a fluorescein isothiocyanate-β-cyclodextrin (FITC-β-CD) as redox-responsive molecular valve blocking the pores, and (c) a FRET donor-acceptor pair of coumarin and FITC integrated within the pore-unlocking event, thereby allowing for monitoring the release of drugs from the pores in real-time. Under non-reducing conditions, when the disulfide bond is intact, the close proximity between coumarin and FITC on the surface of MSNs results in FRET from coumarin to FITC. However, in the presence of the redox stimuli like glutathione (GSH), the disulfide bond is cleaved which leads to the removal of molecular valve (FITC-β-CD), thus triggering drug release and eliminating FRET. By engineering such a FRET-active donor-acceptor structure within the redox-responsive molecular valve, we can monitor the release of the drugs entrapped within the pores of the MSN nanocarrier, following the change in the FRET signal. We have demonstrated that, any exogenous or endogenous change in the GSH concentration will result in a change in the extent of drug release as well as a concurrent change in the FRET signal, allowing us to extend the applications of our FRET-based MSNs for monitoring the release of any type of drug molecule in real-time. PMID:23445171

  18. Dual Stimuli-Responsive Polymer Prodrugs Quantitatively Loaded by Nanoparticles for Enhanced Cellular Internalization and Triggered Drug Release.

    PubMed

    Huang, Mingming; Zhao, Kaijie; Wang, Lei; Lin, Shanqing; Li, Junjie; Chen, Jingbo; Zhao, Chengai; Ge, Zhishen

    2016-05-11

    Direct encapsulation of hydrophobic drugs into amphiphilic block copolymer micelles is frequently subjected to low drug loading efficiency (DLE) and loading content (DLC), as well as lower micellar stability and uncontrollable drug release. In this report, we prepare the copolymer prodrugs (PPEMA-co-PCPTM) via reversible addition-fragmentation chain transfer (RAFT) polymerization of 2-(piperidin-1-yl)ethyl methacrylate (PEMA) and reduction-responsive CPT monomer (CPTM), which were quantitatively encapsulated into poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL) micelles. The polymer prodrug-loaded nanoparticles showed high stability for a long time in aqueous solution or blood serum and even maintain similar size after a lyophilization-dissolution cycle. The tumoral pH (∼6.8)-responsive properties of PPEMA segments endow the micellar cores with triggered transition from neutral to positively charged and swellable properties. The PEG-b-PCL nanoparticles loading polymer prodrugs (PPEMA-b-PCPTM) eliminated burst drug release. Simultaneously, CPT drug release can be triggered by reductive agents and solution pH. At pH 6.8, efficient cellular internalization was achieved due to positively charged cores of the nanoparticles. As compared with nanoparticles loading PCPTM, higher cytotoxicity was observed by the nanoparticles loading PPEMA-b-PCPTM at pH 6.8. Further multicellular tumor spheroid (MCTs) penetration and growth suppression studies demonstrated that high-efficiency penetration capability and significant size shrinkage of MCTs were achieved after treatment by PPEMA-b-PCPTM-loaded nanoparticles at pH 6.8. Therefore, the responsive polymer prodrug encapsulation strategy represents an effective method to overcome the disadvantages of common hydrophobic drug encapsulation approaches by amphiphilic block copolymer micelles and simultaneously endows the nanoparticles with responsive drug release behaviors as well as enhanced cellular internalization and

  19. pH-Responsive Nanoparticles Releasing Tenofovir for The Prevention of HIV Transmission

    PubMed Central

    Zhang, Tao; Sturgis, Timothy F.; Youan, Bi-Botti C.

    2011-01-01

    This study is designed to test the hypothesis that Tenofovir(TNF)ortenofovir disoproxil fumarate (TDF) loaded nanoparticles (NPs)prepared with a blend of poly(lactic-co-glycolic acid) (PLGA) and methacrylic acid copolymer (Eudragit® S-100, or S-100)are noncytotoxic and exhibit significant pH-responsive release of anti-HIV microbicides in presence of human semen. After NPs preparation by emulsification diffusion, their size, encapsulation efficiency (EE%), drug release profile, morphology, and cytotoxicity are characterized by dynamic light scattering, spectrophotometry, transmission electron microscopy, and cellular viability assay/transepithelial electrical resistance measurement, respectively. Cellular uptake was elucidated by fluorescence spectroscopy and confocal microscopy. The NP shavean average size of 250 nm, maximal EE% of 16.1% and 37.2% for TNF and TDF, respectively. There is a 4-fold increase in the drug release rate from 75% S-100 blendin the presence of semen fluid simulant over 72 hr. At a concentration up to 10 mg/ml, the PLGA/S-100 NPs are noncytotoxic for 48 hr to vaginal endocervical/epithelial cells and Lactobacillus crispatus. The particle uptake (~50% in 24hr.) by these vaginal cell lines mostly occurred through caveolin-mediated pathway. These data suggest the promise of using PLGA/S-100 NP as an alternative controlled drug delivery system in intravaginal delivery of an anti-HIV/AIDS microbicide. PMID:21736940

  20. 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

  1. 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

  2. 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

  3. Charge-Reversal APTES-Modified Mesoporous Silica Nanoparticles with High Drug Loading and Release Controllability.

    PubMed

    Wang, Yifeng; Sun, Yi; Wang, Jine; Yang, Yang; Li, Yulin; Yuan, Yuan; Liu, Changsheng

    2016-07-13

    In this study, we demonstrate a facile strategy (DL-SF) for developing MSN-based nanosystems through drug loading (DL, using doxorubicin as a model drug) followed by surface functionalization (SF) of mesoporous silica nanoparticles (MSNs) via aqueous (3-aminopropyl)triethoxysilane (APTES) silylation. For comparison, a reverse functionalization process (i.e., SF-DL) was also studied. The pre-DL process allows for an efficient encapsulation (encapsulation efficiency of ∼75%) of an anticancer drug [doxorubicin (DOX)] inside MSNs, and post-SF allows in situ formation of an APTES outer layer to restrict DOX leakage under physiological conditions. This method makes it possible to tune the DOX release rate by increasing the APTES decoration density through variation of the APTES concentration. However, the SF-DL approach results in a rapid decrease in drug loading capacity with an increase in APTES concentration because of the formation of the APTES outer layer hampers the inner permeability of the DOX drug, resulting in a burst release similar to that of undecorated MSNs. The resulting DOX-loaded DL-SF MSNs present a slightly negatively charged surface under physiological conditions and become positively charged in and extracellular microenvironment of solid tumor due to the protonation effect under acidic conditions. These merits aid their maintenance of long-term stability in blood circulation, high cellular uptake by a kind of skin carcinoma cells, and an enhanced intracellular drug release behavior, showing their potential in the delivery of many drugs beyond anticancer chemotherapeutics. PMID:27314423

  4. Binding and release of drugs into and from thermosensitive poly(N-vinyl caprolactam) nanoparticles.

    PubMed

    Vihola, Henna; Laukkanen, Antti; Hirvonen, Jouni; Tenhu, Heikki

    2002-07-01

    Three model drug substances, the beta-blocking agents nadolol and propranolol and a choline-esterase inhibitor tacrine, were used in order to determine how different drug molecules affect the behavior of thermally responsive polymer nanoparticles composed of poly(N-vinylcaprolactam) (PVCL). Pure PVCL particles in water exist in a swollen state at room temperature, but the size of the particles decreases discontinuously when the temperature is raised above the volume phase transition temperature. At temperatures above this transition temperature, water is expelled out from the nanoscopic hydrogel particles. Light scattering studies revealed that the more hydrophobic drug substances, propranolol and tacrine, considerably swell the PVCL-microgel. The more hydrophilic drug, nadolol, decreased the transition temperature of PVCL particles, whereas the transition temperature values of pure PVCL particles and that of the added propranolol and tacrine were quite similar. Attenuated drug release results showed that the beta-blocking agents were tightly bound to the microgel, and this was more evident at higher temperatures. On the contrary, the release of tacrine across the cellulose membrane was increased when PVCL particles were present. Thus, both physical and chemical properties of the drugs clearly affected their binding to PVCL particles and the release of drugs was affected by the temperature. PMID:12113893

  5. 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. PMID:27150579

  6. 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

  7. Enzyme-responsive intracellular-controlled release using silica mesoporous nanoparticles capped with ε-poly-L-lysine.

    PubMed

    Mondragón, Laura; Mas, Núria; Ferragud, Vicente; de la Torre, Cristina; Agostini, Alessandro; Martínez-Máñez, Ramón; Sancenón, Félix; Amorós, Pedro; Pérez-Payá, Enrique; Orzáez, Mar

    2014-04-25

    The synthesis and characterization of two new capped silica mesoporous nanoparticles for controlled delivery purposes are described. Capped hybrid systems consist of MCM-41 nanoparticles functionalized on the outer surface with polymer ε-poly-L-lysine by two different anchoring strategies. In both cases, nanoparticles were loaded with model dye molecule [Ru(bipy)3](2+). An anchoring strategy involved the random formation of urea bonds by the treatment of propyl isocyanate-functionalized MCM-41 nanoparticles with the lysine amino groups located on the ε-poly-L-lysine backbone (solid Ru-rLys-S1). The second strategy involved a specific attachment through the carboxyl terminus of the polypeptide with azidopropyl-functionalized MCM-41 nanoparticles (solid Ru-tLys-S1). Once synthesized, both nanoparticles showed a nearly zero cargo release in water due to the coverage of the nanoparticle surface by polymer ε-poly-L-lysine. In contrast, a remarkable payload delivery was observed in the presence of proteases due to the hydrolysis of the polymer's amide bonds. Once chemically characterized, studies of the viability and the lysosomal enzyme-controlled release of the dye in intracellular media were carried out. Finally, the possibility of using these materials as drug-delivery systems was tested by preparing the corresponding ε-poly-L-lysine capped mesoporous silica nanoparticles loaded with cytotoxic drug camptothecin (CPT), CPT-rLys-S1 and CPT-tLys-S1. Cellular uptake and cell-death induction were studied. The efficiency of both nanoparticles as new potential platforms for cancer treatment was demonstrated. PMID:24700694

  8. 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

  9. 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

  10. 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

  11. Photothermal release of small molecules from gold nanoparticles in live cells.

    PubMed

    Zandberg, Wesley F; Bakhtiari, Amir Bahman Samsam; Erno, Zach; Hsiao, Dennis; Gates, Byron D; Claydon, Thomas; Branda, Neil R

    2012-08-01

    The ability of gold (Au) nanoparticles (NPs) to generate heat efficiently by absorbing visible and near-infrared (NIR) light holds great promise as a means to trigger chemical and biochemical events near the NPs. Previous demonstrations show that pulsed laser irradiation can selectively elicit the release of a fluorescent dye covalently anchored to the NP surface through a heat-labile linker without measurably changing the temperature of the surroundings. This article reports that the authors demonstrate the biological efficacy of this approach to photodelivery by showing that the decorated Au NPs are rapidly internalized by cells, are stable under physiological conditions, are nontoxic, and exhibit nonlethal photorelease following exposure to pulsed laser radiation. These observations, further supported by the versatility of our delivery motif, reaffirm the potential for further development of nonlethal photothermal therapeutics and their future relevance to such fields as gene therapy and stem-cell differentiation. PMID:22100758

  12. 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.

  13. 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

  14. Glucose cryoprotectant affects glutathione-responsive antitumor drug release from polysaccharide nanoparticles.

    PubMed

    Curcio, Manuela; Blanco-Fernández, Bárbara; Costoya, Alejandro; Concheiro, Angel; Puoci, Francesco; Alvarez-Lorenzo, Carmen

    2015-06-01

    The aim of this work was to prepare polysaccharide-based nanoparticles (NPs) sensitive to glutathione (GSH), and to elucidate the effect of the concentration of glucose used as cryoprotectant during freeze-drying on the GSH-responsiveness. NPs were obtained via ionic interaction between negatively charged polysaccharides, chondroitin sulfate and dermatan sulfate, and the positively charged thiolated chitosan (CSSH), and crosslinking of CSSH before or after the nanoparticles formation with a disulfide-bond containing crosslinker, N,N'-bis(acryloyl)cystamine (BAC). NPs were freeze-dried with glucose at two different concentrations (0.5 and 5.0%w/w) and then characterized as methotrexate delivery systems, studying the effect of GSH concentration on drug release, efficacy against tumor cells and cellular internalization. Non-loaded NPs were highly compatible with murine fibroblasts and showed a suitable size for being used in anticancer therapy. When methotrexate-loaded NPs were freeze-dried with the highest glucose concentration, they lost their responsiveness to GSH concentration in vitro. Drug-loaded NPs were shown to inhibit the growth of tumor cells (HeLa and CHO-K1) with greater efficiency than free methotrexate, disregarding the concentration of glucose used for freeze-drying. Nevertheless, confocal microscopy studies revealed that cellular internalization of NPs freeze-dried with 5.0% glucose is more difficult than for NPs freeze-dried with lower glucose concentration. Thus, concentration of glucose cryoprotectant should be taken into account during development of NPs intended to release the drug as a function of GSH levels, due to the specific interactions of glucose with GSH. PMID:25917641

  15. Computational Modeling of Tumor Response to Drug Release from Vasculature-Bound Nanoparticles

    PubMed Central

    Lowengrub, John; Decuzzi, Paolo; Frieboes, Hermann B.

    2015-01-01

    Systemically injected nanoparticle (NPs) targeting tumor vasculature offer a venue for anti-angiogenic therapies as well as cancer detection and imaging. Clinical application has been limited, however, due to the challenge of elucidating the complex interplay of nanotechnology, drug, and tumor parameters. A critical factor representing the likelihood of endothelial adhesion is the NP vascular affinity, a function of vascular receptor expression and NP size and surface-bound ligand density. We propose a theoretical framework to simulate the tumor response to vasculature-bound drug-loaded NPs and examine the interplay between NP distribution and accumulation as a function of NP vascular affinity, size, and drug loading and release characteristics. The results show that uniform spatial distribution coupled with high vascular affinity is achievable for smaller NPs but not for larger sizes. Consequently, small (100 nm) NPs with high vascular affinity are predicted to be more effective than larger (1000 nm) NPs with similar affinity, even though small NPs have lower drug loading and local drug release compared to the larger NPs. Medium vascular affinity coupled with medium or larger sized NPs is also effective due to a more uniform distribution with higher drug loading and release. Low vascular affinity hampered treatment efficacy regardless of NP size, with larger NPs additionally impeded by heterogeneous distribution and drug release. The results further show that increased drug diffusivity mainly benefits heterogeneously distributed NPs, and would negatively affect efficacy otherwise due to increased wash-out. This model system enables evaluation of efficacy for vascular-targeted drug-loaded NPs as a function of critical NP, drug, and tumor parameters. PMID:26660469

  16. 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

  17. 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

  18. Preparation, characterization of hydrophilic and hydrophobic drug in combine loaded chitosan/cyclodextrin nanoparticles and in vitro release study.

    PubMed

    Jingou, Ji; Shilei, Hao; Weiqi, Liu; Danjun, Wu; Tengfei, Wang; Yi, Xu

    2011-03-01

    The compound nanoparticles of chitosan (CS) and cyclodextrin (CD) loading with hydrophilic and hydrophobic drug simultaneously were prepared via the cross-linking method. Methotrexate (MTX) and calcium folinate (CaF) were selected as the model drugs. The prepared nanoparticles were characterized by FT-IR spectroscopy to confirm the cross-linking reaction between CS and cross-linking agent. X-ray diffraction (XRD) was performed to reveal the form of the drug after encapsulation. The average size of nanoparticles ranged from 308.4 ± 15.22 to 369.3 ± 30.01 nm. The nanoparticles formed were spherical in shape with high zeta potentials (higher than +30mV). In vitro release studies in phosphate buffer saline (pH 7.4) showed an initial burst effect and followed by a slow drug release. Cumulative release data were fitted to an empirical equation to compute diffusional exponent (n), which indicated the non-Fickian trend for drug release. PMID:21112190

  19. 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

  20. 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

  1. 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

  2. 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.

  3. Sub-100 nm gold nanoparticle vesicles as a drug delivery carrier enabling rapid drug release upon light irradiation.

    PubMed

    Niikura, Kenichi; Iyo, Naoki; Matsuo, Yasutaka; Mitomo, Hideyuki; Ijiro, Kuniharu

    2013-05-01

    Previously, we reported gold nanoparticles coated with semifluorinated ligands self-assembled into gold nanoparticle vesicles (AuNVs) with a sub-100 nm diameter in tetrahydrofuran (THF). (1) Although this size is potentially useful for in vivo use, the biomedical applications of AuNVs were limited, as the vesicular structure collapsed in water. In this paper, we demonstrate that the AuNVs can be dispersed in water by cross-linking each gold nanoparticle with thiol-terminated PEG so that the cross-linked vesicles can work as a drug delivery carrier enabling light-triggered release. Rhodamine dyes or anticancer drugs were encapsulated within the cross-linked vesicles by heating to 62.5 °C. At this temperature, the gaps between nanoparticles open, as confirmed by a blue shift in the plasmon peak and the more efficient encapsulation than that observed at room temperature. The cross-linked AuNVs released encapsulated drugs upon short-term laser irradiation (5 min, 532 nm) by again opening the nanogaps between each nanoparticle in the vesicle. On the contrary, when heating the solution to 70 °C, the release speed of encapsulated dyes was much lower (more than 2 h) than that triggered by laser irradiation, indicating that cross-linked AuNVs are highly responsive to light. The vesicles were efficiently internalized into cells compared to discrete gold nanoparticles and released anticancer drugs upon laser irradiation in cells. These results indicate that cross-linked AuNVs, sub-100 nm in size, could be a new type of light-responsive drug delivery carrier applicable to the biomedical field. PMID:23566248

  4. 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

  5. Gold nanoparticle modifies nitric oxide release and vasodilation in rat aorta.

    PubMed

    Silva, Bruno R; Lunardi, Claure N; Araki, Koiti; Biazzotto, Juliana C; Da Silva, Roberto S; Bendhack, Lusiane M

    2014-04-01

    Nitric oxide (NO) plays an important role on several biological functions. Recently, it has been reported the possibility of modifying the NO release profile from the NO donors through its coupling to gold nanoparticles (AuNPs). Thus, AuNPs were synthesized and they were exposed to the NO donor ruthenium complex Cis-[Ru(bpy)2(NO)(4PySH)].(PF6)3 termed (Ru-4PySH)-forming AuNPs-{Ru-4PySH}n cluster. Our results indicate that AuNPs do not modify the maximum effect (ME) and potency (pD2) in the vasodilation induced by Ru-4PySH. Both complexes induce similar vascular relaxation in concentration-dependent way. However, the NO released from the complex AuNPs-{Ru-4PySH}n is lower than Ru-4PySH. Both complexes release only NO(0) specie, but AuNPs-{Ru-4PySH}n releases NO in constant way and exclusively in the extracellular medium. In time-course, Ru-4Py-SH was faster than AuNPs-{Ru-4PySH}n in inducing the maximum vasodilation. Inhibition of soluble guanylyl cyclase (sGC) abolished the vasodilation induced by Ru-4PYSH, but not by AuNPs-{Ru-4PySH}n. Non-selective potassium (K(+)) channel blocker TEA had no effect on the vasodilation induced by AuNPs-{Ru-4PySH}n, but it reduced the potency to Ru-4PySH. In conclusion, our results suggest that AuNPs can reduce the permeability of NO donor Ru-4PySH due to AuNPs-{Ru-4PySH}n cluster formation. AuNPs reduce NO release, but they do not impair the vasodilator effect induced by the NO donor. Ru-4PySH induces vasodilation by sGC and K(+) channels activation, while AuNPs-{Ru-4PySH}n activates mainly sGC. Taken together, these findings represent a new pharmacological strategy to control the NO release which could activate selective biological targets. PMID:24711859

  6. Inclusion of telmisartan in mesocellular foam nanoparticles: drug loading and release property.

    PubMed

    Zhang, Yanzhuo; Jiang, Tongying; Zhang, Qiang; Wang, Siling

    2010-09-01

    Spherical mesocellular foam (MCF) with a continuous 3-D pore system was synthesized using Pluronic 123 triblock polymer (P123) as a surfactant coupled with cetyltrimethyl ammonium bromide (CTAB) as a co-surfactant. The feasibility of the prepared MCF nanoparticles for oral drug delivery was studied. A model drug, telmisartan (TEL), was loaded onto MCF via a procedure involving a combination of adsorption equilibrium and solvent evaporation. The drug-release rate and the drug loading efficiency of spherical MCF were compared with those of fibrous SBA-15. Investigations using nitrogen adsorption, scanning electron microscopy (SEM), transmission electron microscopy (TEM), wide-angle X-ray scattering (WXRS), differential scanning calorimetry (DSC) and HPLC demonstrated the successful incorporation of TEL into the MCF host. It is found that spherical MCF has a high drug loading efficiency up to 42.9% (drug weight/total weight) and higher than that of SBA-15 with a pore diameter of 6.5 nm. It is shown that a fast release rate of TEL was obtained from MCF compared with SBA-15 and pure crystalline TEL using enzyme-free simulated gastric fluid (pH 1.2) and intestinal fluid (pH 6.8). We believe that the present study will help in the design of oral drug delivery systems for the dissolution enhancement of water-insoluble drugs. PMID:20685333

  7. 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

  8. 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

  9. Utilizing chemo-mechanically functionalized oscillating fins to ``catch and release'' nanoparticles in binary flow

    NASA Astrophysics Data System (ADS)

    Liu, Ya; Ma, Yongting; Bhattacharya, Amitabh; Kuksenok, Olga; He, Ximin; Aizenberg, Joanna; Balazs, Anna

    2013-11-01

    In biomimetics, designing an effective ``catch and release'' device for the selective removal of target species from the surrounding solution is critical for developing autonomous sensors and sorters. Using computational simulation, we model an array of oscillating fins that are tethered on the floor of a microchannel and immersed in a binary-fluid stream. During the oscillation, the fins with the specific chemical wetting reach the upper fluid when they are upright and are entirely within the lower stream when they are tilted. We introduce specific adhesive interactions between the fins and particulates in the solution and determine conditions where the oscillating fins can selectively bind (``catch'') target nanoparticles within the upper fluid stream and then release these particles into the lower stream. We isolate the effects of chemical wetting on the fins (e.g., wetting contact angle between fins and fluid) and mechanical parameters (e.g., frequency of fins' oscillations) that lead to the efficient extraction of target species from the upper stream and placement into the lower fluid. Our understanding provides fundamental insights into the system's complex dynamics and mechanism for detection, separation, and purification of multi-component mixtures.

  10. Porous Hollow Fe3O4 Nanoparticles for Targeted Delivery and Controlled Release of Cisplatin

    PubMed Central

    Cheng, Kai; Peng, Sheng; Xu, Chenjie; Sun, Shouheng

    2009-01-01

    We report a new approach to cisplatin storage and release using porous hollow nanoparticles (PHNPs) of Fe3O4. We prepared the PHNPs by controlled oxidation of Fe NPs at 250°C followed by acid etching. The opening pores (~2–4 nm) facilitated the cisplatin diffusion into the cavity of the hollow structure. The porous shell was stable in neutral or basic physiological conditions and cisplatin escape from the cavity through the same pores was diffusion-controlled slow process with t1/2 = 16 hrs. But in low pH (< 6) conditions, the pores were subject to acidic etching, resulting in wider pore gaps and faster release of cisplatin with t1/2 < 4 hrs. Once coupled with Herceptin to the surface, the cisplatin-loaded hollow NPs could target to breast cancer SK-BR-3 cells with IC50 reaching 2.9 μM, much lower than 6.8 μM needed for free cisplatin. Our model experiments indicate that the low pH-responsive PHNPs of Fe3O4 can be exploited as a cisplatin delivery vehicle for target-specific therapeutic applications. PMID:19722635

  11. Quantifying the total ionic release from nanoparticles after particle-cell contact.

    PubMed

    He, Xiao; Pan, Yuanyuan; Zhang, Junzhe; Li, Yuanyuan; Ma, Yuhui; Zhang, Peng; Ding, Yayun; Zhang, Jing; Wu, Zhenqiang; Zhao, Yuliang; Chai, Zhifang; Zhang, Zhiyong

    2015-01-01

    In order to assess the potential hazards of nanoparticles (NPs) releasing, better knowledge about their toxicity to microbes is required. However, it remains controversial whether NPs could exert particles pecifictoxicity. In this study, the toxic impacts of four kinds of rare earth oxides (REO) NPs (La(2)O(3),CeO(2), Gd(2)O(3), and Yb(2)O(3)) on gram-negative Escherichia coli (E. coli) pBR322 were examined. The results indicate that all the tested NPs possessed cytotoxicity against E. coli. To evaluate the ion-related toxicity of REO NPs, the NPs dissolution in the presence of test organisms was quantitatively measured using X-ray absorption fine structure (XAFS) spectroscopy. Our results suggest that NPs-cell contact could facilitate the dissolution of NPs, and the additional ionic release at the particle-cell interface might result in a substantial increase in the ion-related toxicities towards the test organisms. Therefore, the ion-related toxicity of NPs might be grossly underestimated if the additional dissolution of NPs caused by particle-cell contact was overlooked, further leading to a false interpretation of particle-specific toxicity. To the best of our knowledge, this is the first determination of the total NPs dissolution after particle-cell contact. These findings are helpful to advance mechanistic understanding of the toxicity exerted by dissolvable metal-based NPs. PMID:25463714

  12. [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. PMID:27245033

  13. 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

  14. 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

  15. 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

  16. Preparation of complex nano-particles based on alginic acid/poly[(2-dimethylamino) ethyl methacrylate] and a drug vehicle for doxorubicin release controlled by ionic strength.

    PubMed

    Cai, Hong; Ni, Caihua; Zhang, Liping

    2012-01-23

    Monodispersed complex nano-particles were synthesized simply by mixing alginic acid (ALG-H) with poly[(2-dimethylamino) ethyl methacrylate] (PDEMA) in pure water without any surfactants or additives. The structure and properties of the nano-particles were extensively studied. The surface charges and average sizes of the nano-particles were varied with the composition of ALG-H and PDEMA. The nano-particles were formed through electrostatic attraction force, and they were very stable in pure water, but dissociated in salt solutions. An anticancer drug (doxorubicin) was loaded in the nano-particles and released in different saline solutions. The release profiles revealed that the drug release could be controlled by adjusting the pH and salt concentrations. The nano-particles displayed apparent advantages such as simple preparation process, low cost, free of organic solvents, size controllable, biodegradable and biocompatible. PMID:22079138

  17. 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. PMID:26981531

  18. 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

  19. 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). PMID:24892700

  20. Enhanced Cytotoxicity to Cancer Cells by Codelivery and Controlled Release of Paclitaxel-loaded Sirolimus-conjugated Albumin Nanoparticles.

    PubMed

    Behrouz, Hossein; Esfandyari-Manesh, Mehdi; Khoeeniha, Mohammad Kazem; Amini, Mohsen; Shiri Varnamkhasti, Behrang; Atyabi, Fatemeh; Dinarvand, Rassoul

    2016-08-01

    Recently, it is suggested that mTOR signaling pathway is an important mediator in many cancers especially breast cancer. Therefore, effects of sirolimus as a mTOR inhibitor in breast cancer have been studied in combination with paclitaxel with or without controlled release effect. In this work, we prepared a water-soluble formulation of sirolimus-conjugated albumin nanoparticles loaded with paclitaxel, to study the effects of sirolimus concentration when it releases more later than paclitaxel in comparison with sirolimus-paclitaxel-loaded albumin nanoparticles. Also effects of paclitaxel loading on cytotoxic properties of nanoparticles were studied. Sirolimus was succinylated at 42-OH with enzymatic reaction of Candida antarctica lipase B, and then its carboxylic group was activated with EDC/NHS and conjugated to the lysine residues of albumin. Paclitaxel was loaded on albumin surface by nab technique in concentration range of 0-10 μg/mL. Sirolimus-conjugated nanoparticles with 0.01 μg/mL paclitaxel showed lowest cell viability of 44% while it was 53% for non-conjugated nanoparticles in MDA-MB-468 cell lines after 48 h (p-value = 0.003). In MCF-7 cell lines, sirolimus-conjugated nanoparticles with 0.1 μg/mL paclitaxel showed lowest cell viability of 35.69% while it was 48% for non-conjugated nanoparticles after 48 h (p-value = 0.03). We guess that when cancer cell lines arrest in G2-M by anticancer drugs like paclitaxel, Akt activates mTOR to make cells continue living, then inhibiting mTOR can enhance anticancer effects. PMID:26913996

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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. PMID:27155590

  6. 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

  7. Functional mesoporous silica nanoparticles (MSNs) for highly controllable drug release and synergistic therapy.

    PubMed

    Cheng, Yin-Jia; Zeng, Xuan; Cheng, Dong-Bing; Xu, Xiao-Ding; Zhang, Xian-Zheng; Zhuo, Ren-Xi; He, Feng

    2016-09-01

    Synergistic therapy involving two or more therapeutic agents with different anticancer mechanisms represents a promising approach to eradicate chemotherapy-refractory cancers. However, the preparation of a synergistic therapy platform generally involves complicated procedures to encapsulate different therapeutic agents and thereby increases the purification difficulty. In this work, we reported a simple but robust strategy to prepare a highly controllable drug delivery system (DDS) for synergistic cancer therapy. To construct this robust DDS, mesoporous silica nanoparticles (MSNs) were employed as a nanoplatform to encapsulate anticancer drug doxorubicin (DOX). After using a tumor-targeting cellular membrane-penetrating peptide (TCPP) and a mitochondria-targeting therapeutic peptide (TPP) to seal the surface pores via disulfide bonds, these newly developed MSNs can target cancer cells, penetrate cell membrane and rapidly release anticancer drug and mitochondria-targeted peptide in cytoplasm, inducing a remarkable synergistic anticancer effect. The new design concept reported here will promote the development of targeted and smart DDSs for synergistic cancer therapy. PMID:27182657

  8. 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

  9. Slow release of ions from internalized silver nanoparticles modifies the epidermal growth factor signaling response.

    PubMed

    Comfort, Kristen K; Maurer, Elizabeth I; Hussain, Saber M

    2014-11-01

    Due to their distinctive physiochemical properties, including a robust antibacterial activity and plasmonic capability, hundreds of consumer and medical products contain colloidal silver nanoparticles (AgNPs). However, even at sub-toxic dosages, AgNPs are able to disrupt cell functionality, through a yet unknown mechanism. Moreover, internalized AgNPs have the potential to prolong this disruption, even after the removal of excess particles. In the present study, we evaluated the impact, mechanism of action, and continual effects of 50 nm AgNP exposure on epidermal growth factor (EGF) signal transduction within a human keratinocyte (HaCaT) cell line. After AgNP expose, EGF signaling was initially obstructed due to the dissolution of particles into silver ions. However, at longer durations, the internalized AgNPs increased EGF signaling activity. This latter behavior correlated to sustained HaCaT stress, believed to be maintained through the continual dissolution of internalized AgNPs. This study raises concerns that even after exposure ceases, the retained nanomaterials are capable of acting as a slow-release mechanism for metallic ions; continually stressing and modifying normal cellular functionality. PMID:25260222

  10. 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

  11. 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

  12. 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. PMID:17949844

  13. 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.

  14. 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

  15. 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. PMID:25481686

  16. 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

  17. 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

  18. DNA-caged gold nanoparticles for controlled release of doxorubicin triggered by a DNA enzyme and pH.

    PubMed

    Zhang, Zi-Mou; Gao, Peng-Cheng; Wang, Zhi-Fei; Sun, Bai-Wang; Jiang, Yong

    2015-08-21

    DNA polyhedron-caged gold nanoparticles (AuNP) were self-assembled using four-point-star DNAs, with three strands hybridizing to each other and the fourth strand attaching to the AuNPs. The DNA-caged AuNPs can work as nanocarriers for doxorubicin, and controlled release behaviour can be triggered by both a DNA enzyme and by the pH value. PMID:26178750

  19. Protein loading into porous CaCO3 microspheres: adsorption equilibrium and bioactivity retention.

    PubMed

    Balabushevich, N G; Lopez de Guerenu, A V; Feoktistova, N A; Volodkin, D

    2015-01-28

    Formulation of proteins into particulate form is a principal strategy to achieve controlled and targeted delivery, as well as to protect fragile protein molecules. Control over size, mechanical properties, and surface area (porosity) of particulate proteins has been successfully achieved by hard templating under mild conditions using porous CaCO3 microspheres. A crucial step in this approach, which determines protein content, is the loading of proteins into the CaCO3 microspheres. In this study, the adsorption of different proteins into the microspheres has been investigated. Proteins differing in characteristics such as molecular weight and charge have been employed: catalase (Cat), insulin (Ins), aprotinin (Apr), and protamine (Pro). Thermodynamics of adsorption equilibria have been studied, together with quantitative and qualitative analysis of protein loading and distribution in the microspheres. Protein interaction with the CaCO3 microspheres is not limited by the diffusion of protein molecules (protein dimensions are significantly smaller than microsphere pores) but is determined by the protein affinity for the microsphere surface. Cat and Ins bind much more strongly to the microspheres than Apr and Pro, which can be explained by electrostatic attractive forces. Protein binding/release and protein biological activity have been investigated as a function of pH. It is shown that pH variation during the adsorption process plays a principal role and defines not only the amount of protein adsorbed/released but also protein biological activity. Protein adsorption and microsphere elimination (by EDTA) do not affect protein bioactivity. In addition to applications for protein particle/capsule formulations, the findings of this study might help in understanding protein interactions with carbonate minerals such as calcium carbonate, which is used as a natural material for multiple applications. PMID:25493351

  20. 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. PMID:25637067

  1. 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

  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. 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

  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. Heterogeneous polymer composite nanoparticles loaded in situ gel for controlled release intra-vaginal therapy of genital herpes.

    PubMed

    Ramyadevi, D; Rajan, K S; Vedhahari, B N; Ruckmani, K; Subramanian, N

    2016-10-01

    Herpes simplex virus causes serious and contagious genital infections in high percentage of female population world-wide. Acyclovir is a clinically successful antiviral molecule till date, in-spite of limitations as poor solubility, low half-life, reduced oral bioavailability and side effects at higher doses. In the present work, controlled release in situ gelling system loaded with polymeric nanoparticles of acyclovir containing a dose of drug equivalent to 105mg/day has been developed. The formulation containing drug loaded polyvinyl pyrrolidone-Eudragit RSPO hybrid polymeric nanoparticles (Size ∼99±3nm, Zeta ∼+26.1±1.5mV) in 15% Pluronic F-127 gel exhibited improved permeability through vaginal membrane (KP=2.20±0.19×10(-6)cm/s). The nanoparticles showed enhanced viability for vaginal epithelial cell lines up to concentration of 100-250μg/mL. The formulation was evaluated for bioavailability and biodistribution through intra-vaginal administration in rat models. The nanoparticle in situ gel formulation maintained an average therapeutic drug level of 0.6±0.2μg/mL in plasma for 24h. Significant improvement in mean residence time of the drug (12.52±1.12h) was observed with a two-fold increase in the relative bioavailability (AUC0-24h=14.92±2.44μgh/mL) compared to that of the pure drug (7.18±1.79μgh/mL). The tissue distribution was 2-3 folds higher in animals treated with nanoparticles in situ gel compared to that of pure drug. Sustained release of drug in vivo was demonstrated, ensuring the suitability of the formulation for clinical therapy in female population. PMID:27351137

  6. Multifunctional cationic lipid-based nanoparticles facilitate endosomal escape and reduction-triggered cytosolic siRNA release.

    PubMed

    Gujrati, Maneesh; Malamas, Anthony; Shin, Tesia; Jin, Erlei; Sun, Yunlu; Lu, Zheng-Rong

    2014-08-01

    Small interfering RNA (siRNA) has garnered much attention in recent years as a promising avenue for cancer gene therapy due to its ability to silence disease-related genes. Effective gene silencing is contingent upon the delivery of siRNA into the cytosol of target cells and requires the implementation of delivery systems possessing multiple functionalities to overcome delivery barriers. The present work explores the multifunctional properties and biological activity of a recently developed cationic lipid carrier, (1-aminoethyl)iminobis[N-(oleicylcysteinyl-1-amino-ethyl)propionamide]) (ECO). The physicochemical properties and biological activity of ECO/siRNA nanoparticles were assessed over a range of N/P ratios to optimize the formulation. Potent and sustained luciferase silencing in a U87 glioblastoma cell line was observed, even in the presence of serum proteins. ECO/siRNA nanoparticles exhibited pH-dependent membrane disruption at pH levels corresponding to various stages of the intracellular trafficking pathway. It was found that disulfide linkages created during nanoparticle formation enhanced the protection of siRNA from degradation and facilitated site-specific siRNA release in the cytosol by glutathione-mediated reduction. Confocal microscopy confirmed that ECO/siRNA nanoparticles readily escaped from late endosomes prior to cytosolic release of the siRNA cargo. These results demonstrate that the rationally designed multifunctionality of ECO/siRNA nanoparticles is critical for intracellular siRNA delivery and the continuing development of safe and effective delivery systems. PMID:25020033

  7. Effects of pH-sensitive chain length on release of doxorubicin from mPEG-b-PH-b-PLLA nanoparticles

    PubMed Central

    Liu, Rong; He, Bin; Li, Dong; Lai, Yusi; Chang, Jing; Tang, James Z; Gu, Zhongwei

    2012-01-01

    Background Two methoxyl poly(ethylene glycol)-poly(L-histidine)-poly(L-lactide) (mPEG-PH-PLLA) triblock copolymers with different poly(L-histidine) chain lengths were synthesized. The morphology and biocompatibility of these self-assembled nanoparticles was investigated. Methods Doxorubicin, an antitumor drug, was trapped in the nanoparticles to explore their drug-release behavior. The drug-loaded nanoparticles were incubated with HepG2 cells to evaluate their antitumor efficacy in vitro. The effects of poly(L-histidine) chain length on the properties, drug-release behavior, and antitumor efficiency of the nanoparticles were investigated. Results The nanoparticles were pH-sensitive. The mean diameters of the two types of mPEG-PH- PLLA nanoparticle were less than 200 nm when the pH values were 5.0 and 7.4. The nanoparticles were nontoxic to NIH 3T3 fibroblasts and HepG2 cells. The release of doxorubicin at pH 5.0 was much faster than that at pH 7.4. The release rate of mPEG45-PH15-PLLA82 nanoparticles was much faster than that of mPEG45-PH30-PLLA82 nanoparticles at pH 5.0. Conclusion The inhibition effect of mPEG45-PH15-PLLA82 nanoparticles on the growth of HepG2 cells was greater than that of mPEG45-PH30-PLLA82 nanoparticles when the concentration of encapsulated doxorubicin was less than 15 μg/mL. PMID:22923987

  8. Controlled release of β-carotene in β-lactoglobulin-dextran-conjugated nanoparticles' in vitro digestion and transport with Caco-2 monolayers.

    PubMed

    Yi, Jiang; Lam, Tina I; Yokoyama, Wallace; Cheng, Luisa W; Zhong, Fang

    2014-09-01

    Undesirable aggregation of nanoparticles stabilized by proteins may occur at the protein's isoelectric point when the particle has zero net charge. Stability against aggregation of nanoparticles may be improved by reacting free amino groups with reducing sugars by the Maillard reaction. β-Lactoglobulin (BLG)-dextran conjugates were characterized by SDS-PAGE and CD. Nanoparticles (60-70 nm diameter) of β-carotene (BC) encapsulated by BLG or BLG-dextran were prepared by the homogenization-evaporation method. Both BLG and BLG-dextran nanoparticles appeared to be spherically shaped and uniformly dispersed by TEM. The stability and release of BC from the nanoparticles under simulated gastrointestinal conditions were evaluated. Dextran conjugation prevented the flocculation or aggregation of BLG-dextran particles at pH ∼4-5 compared to very large sized aggregates of BLG nanoparticles. The released contents of BC from BLG and BLG-dextran nanoparticles under acidic gastric conditions were 6.2 ± 0.9 and 5.4 ± 0.3%, respectively. The release of BC from BLG-dextran nanoparticles by trypsin digestion was 51.8 ± 4.3% of total encapsulated BC, and that from BLG nanoparticles was 60.9 ± 2.9%. Neither BLG-BC nanoparticles nor the Maillard-reacted BLG-dextran conjugates were cytotoxic to Caco-2 cells, even at 10 mg/mL. The apparent permeability coefficient (Papp) of Caco-2 cells to BC was improved by nanoencapsulation, compared to free BC suspension. The results indicate that BC-encapsulated β-lactoglobulin-dextran-conjugated nanoparticles are more stable to aggregation under gastric pH conditions with good release and permeability properties. PMID:25131216

  9. Microfluidic synthesis of dye-loaded polycaprolactone-block-poly(ethylene oxide) nanoparticles: Insights into flow-directed loading and in vitro release for drug delivery.

    PubMed

    Bains, Aman; Wulff, Jeremy E; Moffitt, Matthew G

    2016-08-01

    Using the fluorescent probe dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) as a surrogate for hydrophobic drugs, we investigate the effects of water content and on-chip flow rate on the multiscale structure, loading and release properties of DiI-loaded poly(ε-caprolactone)-block-poly(ethylene oxide) (PCL-b-PEO) nanoparticles produced in a gas-liquid segmented microfluidic device. We find a linear increase in PCL crystallinity within the nanoparticle cores with increasing flow rate, while mean nanoparticle sizes first decrease and then increase with flow rate coincident with the disappearance and reappearance of long filament nanoparticles. Loading efficiencies at the lower water content (cwc+10wt%) are generally higher (up to 94%) compared to loading efficiencies (up to 53%) at the higher water content (cwc+75wt%). In vitro release times range between ∼2 and 4days for nanoparticles produced at cwc+10wt% and >15days for nanoparticles produced at cwc+75wt%. At the lower water content, slower release of DiI is found for nanoparticles produced at higher flow rate, while at high water content, release times first decrease and then increase with flow rate. Finally, we investigate the effects of the chemical and physical characteristics of the release medium on the kinetics of in vitro DiI release and nanoparticle degradation. This work demonstrates the general utility of dye-loaded nanoparticles as model systems for screening chemical and flow conditions for producing drug delivery formulations within microfluidic devices. PMID:27163840

  10. 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

  11. 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

  12. Photoexpulsion of Surface-Grafted Ruthenium Complexes and Subsequent Release of Cytotoxic Cargos to Cancer Cells from Mesoporous Silica Nanoparticles

    PubMed Central

    Frasconi, Marco; Liu, Zhichang; Lei, Juying; Wu, Yilei; Strekalova, Elena; Malin, Dmitry; Ambrogio, Michael W.; Chen, Xinqi; Botros, Youssry Y.; Cryns, Vincent L.; Sauvage, Jean-Pierre; Stoddart, J. Fraser

    2014-01-01

    Ruthenium(II) polypyridyl complexes have emerged both as promising probes of DNA structure and as anticancer agents because of their unique photophysical and cytotoxic properties. A key consideration in the administration of those therapeutic agents is the optimization of their chemical reactivities to allow facile attack on the target sites, yet avoid unwanted side effects. Here, we present a drug delivery platform technology, obtained by grafting the surface of mesoporous silica nanoparticles (MSNPs) with ruthenium(II) dipyridophenazine (dppz) complexes. This hybrid nanomaterial displays enhanced luminescent properties relative to that of the ruthenium(II) dppz complex in a homogeneous phase. Since the coordination between the ruthenium(II) complex and a monodentate ligand linked covalently to the nanoparticles can be cleaved under irradiation with visible light, the ruthenium complex can be released from the surface of the nanoparticles by selective substitution of this ligand with a water molecule. Indeed, the modified MSNPs undergo rapid cellular uptake, and after activation with light, the release of an aqua ruthenium(II) complex is observed. We have delivered, in combination, the ruthenium(II) complex and paclitaxel, loaded in the mesoporous structure, to breast cancer cells. This hybrid material represents a promising candidate as one of the so-called theranostic agents that possess both diagnostic and therapeutic functions. PMID:23815127

  13. 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. PMID:24365706

  14. 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. PMID:27109701

  15. LbL Assembly of Albumin on Nitric Oxide-Releasing Silica Nanoparticles Using Suramin, a Polyanion Drug, as an Interlayer Linker.

    PubMed

    Chou, Hung-Chang; Chiu, Shih-Jiuan; Hu, Teh-Min

    2015-08-10

    Preformed protein corona of nanoparticles can be utilized as a promising formulation strategy for improving nano drug delivery. Nitric oxide (NO) is a labile molecule with extensive therapeutic implications. In this study, we test whether preformation of protein coatings can enhance the performance of NO-delivering nanoparticles. S-Nitroso (SNO) silica nanoparticles (SNO-SiNPs) were prepared using a nanoprecipitation method. For the first time, bovine serum albumin (BSA) was used to coat NO-releasing nanoparticles, facilitated by a polyanionic drug, suramin, under a layer-by-layer (LbL) scheme. Bare and coated nanoparticles were characterized by zeta-potential, size, and spectroscopic measurements. We demonstrate that albumin/suramin-surface coassembly has advantages in preventing particle aggregation during lyophilization, controlling NO release and exerting an enhanced anticancer effect. PMID:26121207

  16. Release of quercetin from micellar nanoparticles with saturated and unsaturated core forming polyesters--a combined computational and experimental study.

    PubMed

    Hassanzadeh, Salman; Khoee, Sepideh; Beheshti, Abolghasem; Hakkarainen, Minna

    2015-01-01

    Computational and experimental studies were combined to obtain new insight into the widely reported anomalous release mechanism of hydrophobic drug (quercetin) from polymeric micellar nanoparticles. Saturated and unsaturated amphiphilic triblock copolymers from monomethoxy polyethylene glycol (mPEG), poly(butylene adipate) (PBA) and poly(cis-2-butene adipate) (PCBA) (mPEG-PBA-mPEG and mPEG-PCBA-mPEG) were utilized as model polymers to specify the contribution of polymer-micelle degradation and polymer-drug interactions on the observed differences in the release rates by applicable computational investigation and experimental evaluations. Monitoring the size of the micelles through the releasing process together with hydrolytic degradation studies of the core forming polymers proved that the contribution of polymer hydrolysis and micelle degradation on the observed differences in the release rates during the release time window was minimal. The compatibility between quercetin and the core forming polymer is another factor influencing the drug encapsulation and the relative release rate and it was therefore investigated theoretically (using density functional theory (DFT) at B3LYP/6-311(++)G level of theory) and experimentally (FT-IR imaging). The drug-polymer interactions in the core were shown to be much more important than the polymer and/or micelle swelling-dissociation-degradation processes under the studied conditions. PMID:25492006

  17. The role of hyaluronic acid inclusion on the energetics of encapsulation and release of a protein molecule from chitosan-based nanoparticles.

    PubMed

    Al-Qadi, Sonia; Alatorre-Meda, Manuel; Martin-Pastor, Manuel; Taboada, Pablo; Remuñán-López, Carmen

    2016-05-01

    The synergistic effects of the polysaccharides chitosan (CS) and hyaluronic acid (HA) formulated into hybrid nanoparticles are promising for drug delivery. In the present work, we performed a detailed analysis of the molecular interactions involved in the TPP-assisted ionotropic gelation of CS hybrid nanoparticles with the objective of investigating the impact of HA inclusion on the particle formulation and on the in vitro release of insulin (INS) as a protein cargo. To do that, an in-depth thermodynamic study was carried out by isothermal titration calorimetry (ITC), nuclear magnetic resonance (NMR) and differential scanning calorimetry (DSC) techniques. Such analysis allowed us to elucidate the type and extent of interactions established by INS within the hybrid nanoparticles and to get further knowledge on the nature of its release mechanism in vitro. Overall, INS release from the CS nanoparticles was thermodynamically driven, and when including HA a weaker INS binding to the nanoparticles, hence, a faster release rate in vitro were observed. As a negative polyelectrolyte, HA might have sterically blocked the activated sites of CS, such as the amino groups, through chain entanglement, thereby, attenuating the competitive binding interactions of INS. As a consequence, INS might have experienced a spatial exclusion onto the surface of the hybrid nanoparticles to a greater extent which, in turn, would explain its initial abrupt release. PMID:26854581

  18. 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.

  19. 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

  20. 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

  1. Perylene-derived single-component organic nanoparticles with tunable emission: efficient anticancer drug carriers with real-time monitoring of drug release.

    PubMed

    Jana, Avijit; Nguyen, Kim Truc; Li, Xin; Zhu, Pengcheng; Tan, Nguan Soon; Ågren, Hans; Zhao, Yanli

    2014-06-24

    An organic nanoparticle-based drug delivery system with high drug loading efficacy (∼79 wt %) was developed using a perylene-derived photoremovable protecting group, namely, perylene-3,4,9,10-tetrayltetramethanol (Pe(OH)4). The anticancer drug chlorambucil was protected by coupling with Pe(OH)4 to form photocaged nanoparticles (Pe(Cbl)4). The photorelease mechanism of chlorambucil from the Pe(Cbl)4 conjugate was investigated experimentally by high-resolution mass spectrometry and theoretically by density functional theory calculations. The Pe(Cbl)4 nanoparticles perform four important roles: (i) a nanocarrier for drug delivery, (ii) a phototrigger for drug release, (iii) a fluorescent chromophore for cell imaging, and (iv) a photoswitchable fluorophore for real-time monitoring of drug release. Tunable emission of the perylene-derived nanoparticles was demonstrated by comparing the emission properties of the Pe(OH)4 and Pe(Cbl)4 nanoparticles with perylene-3-ylmethanol. These nanoparticles were subsequently employed in cell imaging for investigating their intracellular localization. Furthermore, the in vivo toxicity of the Pe(OH)4 nanoparticles was investigated using the mouse model. Histological tissue analysis of five major organs, i.e., heart, kidney, spleen, liver, and lung, indicates that the nanoparticles did not show any obvious damage to these major organs under the experimental conditions. The current research presents a successful example of integrating multiple functions into single-component organic nanoparticles for drug delivery. PMID:24824959

  2. 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

  3. 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. PMID:24578624

  4. 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

  5. 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

  6. 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

  7. Exposure characteristics of ferric oxide nanoparticles released during activities for manufacturing ferric oxide nanomaterials.

    PubMed

    Xing, Mingluan; Zhang, Yuanbao; Zou, Hua; Quan, Changjian; Chang, Bing; Tang, Shichuan; Zhang, Meibian

    2015-02-01

    The exposure characteristics of Fe2O3 nanoparticles (NPs) released in a factory were investigated, as exposure data on this type of NP is absent. The nature of the particles was identified in terms of their concentrations [i.e. number concentration (NC(20-1000 nm)), mass concentration (MC(100-1000 nm)), surface area concentration (SAC(10-1000 nm))], size distribution, morphology and elemental composition. The relationships between different exposure metrics were determined through analyses of exposure ranking (ER), concentration ratios (CR), correlation coefficients and shapes of the particle concentration curves. Work activities such as powder screening, material feeding and packaging generated higher levels of NPs as compared to those of background particles (p < 0.01). The airborne Fe2O3 NPs exhibited a unimodal size distribution and a spindle-like morphology and consisted predominantly of the elements O and Fe. Periodic and activity-related characteristics were noticed in the temporal variations in NC(20-1000 nm) and SAC(10-1000 nm). The modal size of the Fe2O3 NPs remained relatively constant (ranging from 10 to 15 nm) during the working periods. The ER, CR values and the shapes of NC(20-1000 nm) and SAC(10-1000 nm) curves were similar; however, these were significantly different from those for MC(100-1000 nm). There was a high correlation between NC(20-1000 nm) and SAC(10-1000 nm), and relatively lower correlations between the two and MC(100-1000 nm). These findings suggest that the work activities during the manufacturing processes generated high levels of primary Fe2O3 NPs. The particle concentrations exhibited periodicity and were activity dependent. The number and SACs were found to be much more relevant metrics for characterizing NPs than was the mass concentration. PMID:25703513

  8. 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

  9. Variation of the crystal growth of mesoporous silica nanoparticles and the evaluation to ibuprofen loading and release.

    PubMed

    Kamarudin, N H N; Jalil, A A; Triwahyono, S; Artika, V; Salleh, N F M; Karim, A H; Jaafar, N F; Sazegar, M R; Mukti, R R; Hameed, B H; Johari, A

    2014-05-01

    Mesoporous silica nanoparticles (MSNs) were synthesized with variable microwave power in the range of 100-450 W, and the resulting enhancement of MSN crystal growth was evaluated for the adsorption and release of ibuprofen. X-ray diffraction (XRD) revealed that the MSN prepared under the highest microwave power (MSN450) produced the most crystallized and prominent mesoporous structure. Enhancement of the crystal growth improved the hexagonal order and range of silica, which led to greater surface area, pore width and pore volume. MSN450 exhibited higher ibuprofen adsorption (98.3 mg/g), followed by MSN300(81.3 mg/g) and MSN100(74.1 mg/g), confirming that more crystallized MSN demonstrated higher adsorptivity toward ibuprofen. Significantly, MSN450 also contained more hydroxyl groups that provided more adsorption sites. In addition, MSN450 exhibited comparable ibuprofen adsorption with conventionally synthesized MSN, indicating the potential of microwave treatment in the synthesis of related porous materials. In vitro drug release was also investigated with simulated biological fluids and the kinetics was studied under different pH conditions. MSN450 showed the slowest release rate of ibuprofen, followed by MSN300 and MSN100. This was due to the wide pore diameter and longer range of silica order of the MSN450. Ibuprofen release from MSN450 at pH 5 and 7 was found to obey a zero-order kinetic model, while release at pH 2 followed the Kosmeyer-Peppas model. PMID:24594025

  10. Formulation and characterization of 5-Fluorouracil enteric coated nanoparticles for sustained and localized release in treating colorectal cancer.

    PubMed

    Tummala, Shashank; Satish Kumar, M N; Prakash, Ashwati

    2015-07-01

    5-Fluorouracil is used in the treatment of colorectal cancer along with oxaliplatin as first line treatment, but it is having lack of site specificity and poor therapeutic effect. Also toxic effects to healthy cells and unavailability of major proportion of drug at the colon region remain as limitations. Toxic effects prevention and drug localization at colon area was achieved by preparing enteric-coated chitosan polymeric nanoparticles as it can be delivered directly to large bowel. Enteric coating helps in preventing the drug degradation at gastric pH. So the main objective was to prepare chitosan polymeric nanoparticles by solvent evaporation emulsification method by using different ratios of polymer (1:1, 1:2, 1:3, 1:4). Optimized polymer ratio was characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD), entrapment efficiency and particle size and further subjected to enteric coating. In vitro drug release studies were done using dialysis bag technique using simulated fluids at various pH (1.2, 4.5, 7.5, 7.0) to mimic the GIT tract. 5-FU nanoparticles with drug: polymer ratio of 1:2 and 1:3 has shown better particle size (149 ± 1.28 nm and 138 ± 1.01 nm respectively), entrapment efficiency (48.12 ± 0.08% and 69.18 ± 1.89 respectively). 5-FU E1 has shown better drug release after 4 h and has shown 82% drug release till 24 h in a sustained manner comparable to the non-enteric coated tablets, which released more than 50% of the drug before entering the colon region. So we can conclude that nanoparticles prepared by this method using the same polymer with the optimized ratio can represent as potential drug delivery approach for effective delivery of the active pharmaceutical ingredient to the colorectal tumors. PMID:26106279

  11. Fluorescent boronate-based polymer nanoparticles with reactive oxygen species (ROS)-triggered cargo release for drug-delivery applications.

    PubMed

    Jäger, Eliézer; Höcherl, Anita; Janoušková, Olga; Jäger, Alessandro; Hrubý, Martin; Konefał, Rafał; Netopilik, Miloš; Pánek, Jiří; Šlouf, Miroslav; Ulbrich, Karel; Štěpánek, Petr

    2016-03-24

    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. PMID:26961769

  12. 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

  13. 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

  14. 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. PMID:24121422

  15. 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

  16. 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

  17. Targeted and controlled release delivery of daunorubicin to T-cell acute lymphoblastic leukemia by aptamer-modified gold nanoparticles.

    PubMed

    Danesh, Noor Mohammad; Lavaee, Parirokh; Ramezani, Mohammad; Abnous, Khalil; Taghdisi, Seyed Mohammad

    2015-07-15

    Clinical administration of daunorubicin (Dau) in treatment of leukemia has been limited by its cardiotoxicity. Targeted delivery of chemotherapy drugs could reduce their side effects and increase the therapeutic efficacy of these drugs. Biocompatibility and large surface area of gold nanoparticles (AuNPs) make these nanoparticles great candidates for biomedical applications. In this study sgc8c aptamer (Apt)-Dau-AuNPs complex was designed and evaluated for treatment of Molt-4 cells (human acute lymphoblastic leukemia T-cell, target). Apt-Dau-AuNPs complex formation was analyzed by fluorometric analysis and gel retardation assay. Dau release profiles from the complex were evaluated in pHs 5.5 and 7.4. For cytotoxic studies (MTT assay) U266 (B lymphocyte human myeloma, nontarget) and Molt-4 cells (target) were treated with Dau Apt-Dau conjugate and Apt-Dau-AuNPs complex. Internalization was monitored by flow cytometry and confocal imaging. 12 μM Dau was efficiently loaded onto 1 mL of Apt-modified AuNPs. Dau was released from the complex in a pH-dependent manner (higher rate of release at pH 5.5). The results of flow cytometry analysis and confocal imaging showed that the complex was effectively internalized into Molt-4 cells, but not into U266 cells. The results of MTT assay also confirmed the internalization data. Apt-Dau-AuNPs complex was less cytotoxic in U266 cells compared to Dau alone and even Apt-Dau conjugate. The complex was more cytotoxic in target cells in comparison with Dau alone and even Apt-Dau conjugate. In conclusion, Apt-Dau-AuNPs complex was able to selectively target Molt-4 cells. Another advantage of this system was pH-dependent release of drug from the complex. Furthermore, this complex has characteristics which make it ideal for clinical use. PMID:25936625

  18. Monodisperse nanoparticles from self-assembling amphiphilic cyclodextrins: modulable tools for the encapsulation and controlled release of pharmaceuticals.

    PubMed

    Mendez-Ardoy, Alejandro; Gómez-García, Marta; Gèze, Annabelle; Putaux, Jean-Luc; Wouessidjewe, Denis; Ortiz Mellet, Carmen; Defaye, Jacques; García Fernández, José M; Benito, Juan M

    2012-07-01

    Selective chemical functionalization of cyclodextrins (CDs) is a readily amenable methodology to produce amphiphilic macromolecules endowed with modulable self-organizing capabilities. Herein, the synthesis of well-defined amphiphilic CD derivatives, with a "skirt-type" architecture, that incorporate long-chain fatty esters at the secondary hydroxyl rim and a variety of chemical functionalities (e. g. iodo, bromo, azido, cysteaminyl or isothiocyanato) at the primary hydroxyls rim is reported. Nanoprecipitation of the new CD facial amphiphiles, or binary mixtures of them, resulted in nanoparticles with average hydrodynamic diameters ranging from 100 to 240 nm that were stable in suspension for several months. The precise size, zeta potential and topology of the nanoparticles are intimately dependent on the functionalization pattern at the CD scaffold. Highly efficient molecular encapsulation capabilities of poorly bioavailable drugs such as diazepam (DZ) were demonstrated for certain derivatives, the drug release profile being dependent on the type of formulation (nanospheres or nanocapsules). The efficiency and versatility of the synthetic strategy, together with the possibility of exploiting the reactivity of the functional groups at the nanoparticle surface, offer excellent opportunities to further manipulate the carrier capabilities of this series of amphiphilic CDs from a bottom-up approach. PMID:22571191

  19. 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

  20. Enhanced Loading and Release of Non-Steroidal Anti-Inflammatory Drugs from Silica-Based Nanoparticle Carriers.

    PubMed

    Mohammadzadeh, Mostafa; Nourbakhsh, Mohammad Sadegh; Khodaverdi, Elham; Hadizadeh, Farzin; Omid Malayeri, Sina

    2016-09-01

    Silica nanoparticles can be potentially considered the carriers of controlled drug systems. In this research, non-steroidal anti-inflammatory drugs were used. Diclofenac sodium and piroxicam were loaded on the considered nanosilica using solvent evaporation method. To prove drug encapsulation on the nanosilica and its rate, infrared spectroscopy, X-ray diffraction, and BET were used, and after proving the existence of the drug in the nanosilica matrix and determining the amount of loading, dissolution test was performed in an environment similar to that of stomach and intestine in terms of pH. Drug loading percentage showed that over 90% of drugs were loaded on nanosilica. Dissolution tests in stomach pH environment showed the control samples (drug without SBA-15) released considerable amount of drugs (about 90%) within first 15 min, when it was about 10-20% for the matrixes. Furthermore, release rate of drugs from matrixes has shown slower rate in comparison with control samples. It was indicated nanosilica has the ability of retaining the drugs in acidic pH and prevented their release. Furthermore, the drugs were released in a controlled manner in small intestine, which is the main absorption site. PMID:27062095

  1. Sustained release of VEGF from PLGA nanoparticles embedded thermo-sensitive hydrogel in full-thickness porcine bladder acellular matrix

    NASA Astrophysics Data System (ADS)

    Geng, Hongquan; Song, Hua; Qi, Jun; Cui, Daxiang

    2011-12-01

    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.

  2. 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

  3. Integrin-targeted zwitterionic polymeric nanoparticles with acid-induced disassembly property for enhanced drug accumulation and release in tumor.

    PubMed

    Huang, Pingsheng; Song, Huijuan; Wang, Weiwei; Sun, Yu; Zhou, Junhui; Wang, Xue; Liu, Jinjian; Liu, Jianfeng; Kong, Deling; Dong, Anjie

    2014-08-11

    Reasonably structural design of nanoparticles (NPs) to combine functions of prolonged systemic circulation, enhanced tumor targeting and specific intracellular drug release is crucial for antitumor drug delivery. Combining advantages of Arg-Gly-Asp (RGD) for active tumor targeting, zwitterionic polycarboxybetaine methacrylate (PCB) for prolonged systemic circulation, poly(2-(diisopropylamino) ethyl methacrylate) (PDPA) for acid-triggered intracellular release, novel RGD-PCB-b-PDPA (RGD-PCD) block copolymers were prepared via reversible addition-fragmentation chain transfer (RAFT) polymerization and followed by functionalization with RGD. Doxorubicine (DOX) was encapsulated within the RGD-PCD NPs as model medicine (RGD-PCD/DOX NPs). With ultra pH-sensitivity of PDPA, the drug release was restrained at pH 7.4 for only 24% within 36 h, which was increased to 60% at pH 6.0 within 24 h, and released more rapidly at pH 5.0 for 100% within 5 h, indicating that the RGD-PCD/DOX NPs were able to turn drug release "off" at neutral pH (e.g., systemic circulation) whereas "on" under acidic conditions (e.g., inside endo/lysosomes). Furthermore, the results of fluorescence microscopy and flow cytometry analysis demonstrated improved internalization of RGD-PCD/DOX NPs in HepG2 cells via integrin-mediated endocytosis with rapid DOX release intracellularly. Consequently, the RGD-PCD/DOX NPs showed considerable cytotoxicity against HepG2 and HeLa cells in comparison with free DOX. Importantly, the RGD-PCD/DOX NPs exhibited little protein adsorption property with excellent serum stability, which led to prolonged systemic circulation and enhanced tumor accumulation in tumor-bearing nude mice. Therefore, this multifunctional RGD-PCD NPs, which represented the flexible design approach, showed great potential for the development of novel nanocarriers in tumor-targeted drug delivery. PMID:25054812

  4. 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

  5. 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

  6. Lactosylated PLGA nanoparticles containing ϵ-polylysine for the sustained release and liver-targeted delivery of the negatively charged proteins.

    PubMed

    Zhou, Ping; An, Tong; Zhao, Chuan; Li, Yuan; Li, Rongshan; Yang, Rui; Wang, Yinsong; Gao, Xiujun

    2015-01-30

    The acidic internal pH environment, initial burst release and lack of targeting property are main limitations of poly(lactide-co-glycolide) (PLGA) nanoparticles for carrying proteins. In this study, ϵ-polylysine (ϵ-PL) was used as an anti-acidic agent and a protein protectant to prepare PLGA nanoparticles for the protein delivery. To obtain the liver-targeting capability, lactosylated PLGA (Lac-PLGA) was synthesized by conjugation of lactose acid to PLGA at both ends, and then used to prepare nanoparticles containing ϵ-PL by the nanoprecipitation method. Bovine serumal bumin (BSA), a negatively charged protein, was efficiently loaded into Lac-PLGA/ϵ-PL nanoparticles and exhibited significant decreased burst release in vitro, sustained release in the blood and increased liver distribution in mice after intravenous injections. The enhanced stability of BSA was due to its electrical interaction with ϵ-PL and the neutralized internal environment of nanoparticles. In conclusion, Lac-PLGA/ϵ-PL nanoparticle system can be used as a promising carrier for the negatively charged proteins. PMID:25510599

  7. 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

  8. 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...

  9. Biodegradable poly(lactide-co-glycolide) nanoparticle assembly for continuous release of bioactive agents from medical devices

    PubMed Central

    Lo, Catherine T.; Van Tassel, Paul R.; Saltzman, W. Mark

    2010-01-01

    Controlled delivery of therapeutic agents from medical devices can improve their safety and effectiveness in vivo, by ameliorating the surrounding tissue responses and thus maintaining the functional integrity of the devices. Previously, we presented a new method for providing simultaneous controlled delivery from medical devices, by surface assembly of biodegradable polymer nanoparticles (NPs) encapsulating fluorescent dyes. Here, we continue our investigation with NPs loaded with therapeutic agents, dexamethasone (DEX) or plasmid DNA, and evaluated the bioactivity of the released molecules with macrophage cells associated with inflammation. Over a period of one week, NPs encapsulating DEX released 24.9 ± 0.8 ng from the probe surface and was successful at suppressing macrophage cell growth by 40 ± 10%. This percentage of suppression corresponded to ∼100% drug delivery efficiency, in comparison with the unencapsulated drug. DNA NP coatings, in contrast, released ∼1 ng of plasmid DNA and were effective at transfecting macrophage cells to express the luciferase gene at 300 ± 200 relative luminescence/mg total protein. This amount of luciferase activity corresponded to 100% gene delivery efficiency. Thus, NP coatings were capable of providing continuous release of bioactive agents in sufficient quantities to induce relevant biological effects in cell culture studies. These coatings also remained intact, even after 14 days of incubation with phosphate buffered saline. Although the maximum loading for NP coatings is inherently lower than the more established matrix coating, our study suggests that the NP coatings are a more versatile and efficient approach toward drug delivery or gene delivery from a medical device surface and are perhaps best suited for continuous release of highly potent therapeutic agents. PMID:20149428

  10. Controlling the burst release of amorphous drug-polysaccharide nanoparticle complex via crosslinking of the polysaccharide chains.

    PubMed

    Nguyen, Minh-Hiep; Tran, The-Thien; Hadinoto, Kunn

    2016-07-01

    High-payload amorphous drug-polysaccharide nanoparticle complex (or nanoplex in short) represents a new class of supersaturating drug delivery systems intended for bioavailability enhancement of poorly-soluble drugs. Not unlike other nanoscale amorphous formulations, the nanoplex exhibits fast dissolution characterized by a burst drug release pattern. While the burst release is ideal for supersaturation generation in the presence of crystallization inhibitor, it is not as ideal for passive targeting drug delivery applications in which the nanoplex must be delivered by itself. Herein we developed nanoplex exhibiting controlled release via crosslinking of the polysaccharide chains onto which the drug molecules were electrostatically bound to. Curcumin and chitosan were used, respectively, as the drug and polysaccharide models with amine-reactive disuccinimidyl tartrate as the crosslinking agent. The crosslinked nanoplex exhibited improved morphology (i.e. smaller size, more spherical, and higher uniformity) that signified its more condensed structure. A twenty-fold reduction in the initial burst release rate with a threefold reduction in the overall dissolution rate was obtained after crosslinking. The slower dissolution was attributed to the more condensed structure of the crosslinked nanoplex that enhanced its dissociation stability in phosphate buffered saline. The reduction in the dissolution rate was proportional to the degree of crosslinking that was governed by the crosslinker to amine ratio. The crosslinking caused slight reductions in the payload and zeta potential of the nanoplex, but with no adverse effect on the cytotoxicity. This proof-of-concept study successfully demonstrated the use of polysaccharide crosslinking to control the drug release from high-payload amorphous drug nanoplex. PMID:27179586

  11. Encapsulation of beraprost sodium in nanoparticles: analysis of sustained release properties, targeting abilities and pharmacological activities in animal models of pulmonary arterial hypertension.

    PubMed

    Ishihara, Tomoaki; Hayashi, Erika; Yamamoto, Shuhei; Kobayashi, Chisa; Tamura, Yuichi; Sawazaki, Ryoichi; Tamura, Fumiya; Tahara, Kayoko; Kasahara, Tadashi; Ishihara, Tsutomu; Takenaga, Mitsuko; Fukuda, Keiichi; Mizushima, Tohru

    2015-01-10

    Prostaglandin I2 (PGI2) and its analogues (such as beraprost sodium, BPS) are beneficial for the treatment of pulmonary arterial hypertension (PAH). The encapsulation of BPS in nanoparticles to provide sustained release and targeting abilities would improve both the therapeutic effect of BPS on PAH and the quality of life of patients treated with this drug. BPS was encapsulated into nanoparticles prepared from a poly(lactic acid) homopolymer and monomethoxy poly(ethyleneglycol)-poly(lactide) block copolymer. The accumulation of nanoparticles in damaged pulmonary arteries was examined using fluorescence-emitting rhodamine S-encapsulated nanoparticles. The monocrotaline-induced PAH rat model and the hypoxia-induced mouse model were used to examine the pharmacological activity of BPS-encapsulated nanoparticles. A nanoparticle, named BPS-NP, was selected among various types of BPS-encapsulated nanoparticles tested; this was based on the sustained release profile in vitro and blood clearance profile in vivo. Fluorescence-emitting rhodamine S-encapsulated nanoparticles were prepared in a similar manner to that of BPS-NP, and showed accumulation and prolonged residence in monocrotaline-damaged pulmonary peripheral arteries. Intravenous administration of BPS-NP (once per week, 20μg/kg) protected against monocrotaline-induced pulmonary arterial remodeling and right ventricular hypertrophy. The extent of this protection was similar to that observed with oral administration (once per day, 100μg/kg) of BPS alone. The once per week intravenous administration of BPS-NP (20μg/kg) also exhibited an ameliorative effect on hypoxia-induced pulmonary arterial remodeling and right ventricular hypertrophy. The beneficial effects of BPS-NP on PAH animal models seem to be mediated by its sustained release and tissue targeting profiles. BPS-NP may be useful for the treatment of PAH patients due to reduced dosages and frequency of BPS administration. PMID:25449809

  12. Sub-100 nm biodegradable nanoparticles: in vitro release features and toxicity testing in 2D and 3D cell cultures

    NASA Astrophysics Data System (ADS)

    Biondi, Marco; Guarnieri, Daniela; Yu, Hui; Belli, Valentina; Netti, Paolo Antonio

    2013-02-01

    A big challenge in tumor targeting by nanoparticles (NPs), taking advantage of the enhanced permeability and retention effect, is the fabrication of small size devices for enhanced tumor penetration, which is considered fundamental to improve chemotherapy efficacy. The purposes of this study are (i) to engineer the formulation of doxorubicin-loaded poly(d,l-lactic-co-glycolic acid) (PLGA)-block-poly(ethylene glycol) (PEG) NPs to obtain <100 nm devices and (ii) to translate standard 2D cytotoxicity studies to 3D collagen systems in which an initial step gradient of the NPs is present. Doxorubicin release can be prolonged for days to weeks depending on the NP formulation and the pH of the release medium. Sub-100 nm NPs are effectively internalized by HeLa cells in 2D and are less cytotoxic than free doxorubicin. In 3D, <100 nm NPs are significantly more toxic than larger ones towards HeLa cells, and the cell death rate is affected by the contributions of drug release and device transport through collagen. Thus, the reduction of NP size is a fundamental feature from both a technological and a biological point of view and must be properly engineered to optimize the tumor response to the NPs.

  13. pH-Responsive hydrogels containing PMMA nanoparticles: an analysis of controlled release of a chemotherapeutic conjugate and transport properties

    PubMed Central

    Schoener, Cody A.; Peppas, Nicholas A.

    2012-01-01

    Biopolymers composed of a pH-responsive, hydrophilic poly(methacrylic acid – grafted – ethylene glycol) (P(MAA-g-EG)) network polymerized in the presence of PMMA nanoparticles were designed for the oral delivery of chemotherapeutics for the treatment of colon cancer. An inulin-doxorubicin conjugate, designed to target the colon and improve doxorubicin efficacy, was loaded into these polymer carriers at an efficiency of 54%. Release studies indicated these polymer carriers minimized conjugate release in low pH conditions and released the conjugate at neutral pH conditions using a two – step pH experiment modeling the stomach and the small intestine. At lower concentration levels, the presence of the polymer carriers did not disrupt tight junctions as determined by transepithelial electrical resistance studies using Caco-2 and HT29-MTX cell lines which are an accurate model of the GI tract epithelia. Permeability values of unmodified doxorubicin and the inulin-doxorubicin conjugate in the presence of the polymer carriers were also determined using the same cell models and ranged from 1.87 – 3.80 × 10−6 cm/s. PMID:23683036

  14. Double targeting, controlled release and reversible delivery of daunorubicin to cancer cells by polyvalent aptamers-modified gold nanoparticles.

    PubMed

    Taghdisi, Seyed Mohammad; Danesh, Noor Mohammad; Lavaee, Parirokh; Emrani, Ahmad Sarreshtehdar; Hassanabad, Koroush Yousefi; Ramezani, Mohammad; Abnous, Khalil

    2016-04-01

    Clinical use of daunorubicin (Dau) in treatment of leukemia has been restricted because of its cardiotoxicity. Targeted delivery of anticancer drugs could decrease their off-target effects and enhance their efficacy. In this study a modified polyvalent aptamers (PA)-Daunorubicin (Dau)-Gold nanoparticles (AuNPs) complex was designed and its efficacy was assessed in Molt-4 cells (human acute lymphoblastic leukemia T-cell, target). Dau was efficiently loaded (10.5 μM) onto 1mL of PA-modified AuNPs. Dau was released from the PA-Dau-AuNPs complex in a pH-sensitive manner (faster release at pH5.5). The results of flow cytometry analysis indicated that the PA-Dau-AuNPs complex was efficiently internalized into target cells, but not into nontarget cells. The results of MTT assay were consistent with the internalization data. PA-Dau-AuNPs complex had less cytotoxicity in U266 cells compared to Dau alone and even Apt-Dau-AuNPs complex. The PA-Dau-AuNPs complex had more cytotoxicity in Molt-4 cells compared to Dau alone and even Apt-Dau-AuNPs complex. Cytotoxicity of PA-Dau-AuNPs complex was effectively antagonized using antisense of polyvalent aptamers. In conclusion, the designed drug delivery system inherited the properties of efficient drug loading, tumor targeting, pH-dependent drug release and controllable delivery of Dau to tumor cells. PMID:26838906

  15. 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. PMID:26730700

  16. Effects of titania nanoparticles on phosphorus fractions and its release in resuspended sediments under UV irradiation.

    PubMed

    Luo, Zhuanxi; Wang, Zhenhong; Li, Qingzhao; Pan, Qikun; Yan, Changzhou

    2010-02-15

    Little is known about the effects of nano-TiO(2) on the transformation and transport of phosphorus (P) in resuspended sediments. Chemical sequential extraction was used to investigate P fractions and its release in resuspended sediments under the influence of nano-TiO(2) and UV irradiation. The results showed that the contents of sediment P in all fractions decreased with increasing nano-TiO(2) concentration in UV irradiation, while increased in the dark controls. Furthermore, P release from all fractions was greater in UV irradiation than in the controls. Elevated concentrations (10-50 mg L(-1)) of nano-TiO(2) in UV irradiation significantly facilitated the release of P from organic and Fe oxide fractions, possibly resulting from the partial photo-degradation of organic matter and photochemical transformation of Fe oxides. Apparently, nano-TiO(2) in UV irradiation did not immobilize the loosely sorbed P and reductant soluble P release from the resuspended sediments, possible because (1) some of P released from those fractions were refurnished by the P released from OM; (2) photocatalysis of nano-TiO(2) reduced binding capacity of the resuspended sediments. Our results suggest that the photocatalysis of nano-TiO(2) may offer the potential to regulate the transformation and transport of sediment P in the aquatic environment. PMID:19850408

  17. 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

  18. 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

  19. 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.

  20. Targeted tumor delivery and controlled release of neuronal drugs with ferritin nanoparticles to regulate pancreatic cancer progression.

    PubMed

    Lei, Yifeng; Hamada, Yoh; Li, Jun; Cong, Liman; Wang, Nuoxin; Li, Ying; Zheng, Wenfu; Jiang, Xingyu

    2016-06-28

    Pancreatic cancer is a lethal malignancy whose progression is highly dependent on the nervous microenvironment. This study develops neural drug-loaded ferritin nanoparticles (Ft NPs) to regulate the nervous microenvironment, in order to control the pancreatic cancer progression. The drug-loaded Ft NPs can target pancreatic tumors via passive targeting of EPR effects of tumors and active targeting via transferrin receptor 1 (TfR1) binding on cancer cells, with a triggered drug release in acidic tumor environment. Two drugs, one activates neural activity (carbachol), the other impairs neural activity (atropine), are encapsulated into the Ft NPs to form two kinds of nano drugs, Nano-Cab NPs and Nano-Ato NPs, respectively. The activation of the nervous microenvironment by Nano-Cab NPs significantly promotes the pancreatic tumor progression, whereas the blockage of neural niche by Nano-Ato NPs remarkably impairs the neurogenesis in tumors and the progression of pancreatic cancer. The Ft-based nanoparticles thus comprise an effective and safe route of delivery of neural drugs for novel anti-cancer therapy. PMID:27046157

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. Development of a long-acting, protein-loaded, redox-active, injectable gel formed by a polyion complex for local protein therapeutics.

    PubMed

    Ishii, Shiro; Kaneko, Junya; Nagasaki, Yukio

    2016-04-01

    Although cancer immunotherapies are attracting much attention, it is difficult to develop bioactive proteins owing to the severe systemic toxicity. To overcome the issue, we designed new local protein delivery system by using a protein-loaded, redox-active, injectable gel (RIG), which is formed by a polyion complex (PIC) comprising three components, viz., cationic polyamine-poly(ethylene glycol)-polyamine triblock copolymer possessing ROS-scavenging moieties as side chains; anionic poly(acrylic acid); and a protein. The mixture formed the protein-loaded PIC flower micelles at room temperature, which immediately converted to a gel with high mechanical strength upon exposure to physiological conditions. Because the protein electrostatically interacts with the PIC gel network, RIG provided a sustained release of the protein without a significant initial burst, regardless of the types of proteins in vitro, and much longer retention of the protein at the local injection site in mice than that of the naked protein. Subcutaneous injections of IL-12@RIG in the vicinity of tumor tissue showed remarkable tumor growth inhibition in tumor-bearing mice, compared to that observed with injection of IL-12 alone, suppressing adverse events caused by IL-12-induced ROS. Our results indicate that RIG has potential as a platform technology for an injectable sustained-release carrier for proteins. PMID:26828685

  7. 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

  8. 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

  9. 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

  10. 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

  11. Biocompatible graphene oxide nanoparticle-based drug delivery platform for tumor microenvironment-responsive triggered release of doxorubicin.

    PubMed

    Zhao, Xubo; Liu, Lei; Li, Xiaorui; Zeng, Jin; Jia, Xu; Liu, Peng

    2014-09-01

    A facile strategy was established to develop a drug delivery system (DDS) based on the graphene oxide nanoparticles (GON) with suitable size and shape to deliver drug effectively, by grafting the biocompatible PEGylated alginate (ALG-PEG) brushes onto the GON via the disulfide bridge bond. TEM analysis and drug-loading performance revealed that the 3-D nanoscaled, biocompatible, reduction-responsive nanocarriers (GON-Cy-ALG-PEG) were spherical in shape with diameters of 94.73 ± 9.56 nm. They possessed high doxorubicin (DOX)-loading capacity and excellent encapsulation efficiency, owing to their unique 3-D nanoscaled structure. They also had excellent stability in simulated physiological conditions and remarkable biocompatibility. Importantly, the in vitro release showed that the platform could not only prevent the leakage of the loaded DOX under physiological conditions but also detach the cytamine (Cy) modified PEGylated alginate (Cy-ALG-PEG) moieties, response to glutathione (GSH). Confocal microscopy and WST-1 assays provided clear evidence of the DOX-loaded GON-Cy-ALG-PEG endocytosis, whereas the drug-loaded nanocarriers exhibited high cytotoxicity to model cells. Furthermore, the cell apoptosis also was monitored via Flow cytometry. The results indicated that the DOX-loaded nanocarriers presented favorable efficiency of cell apoptosis. So these findings demonstrate that the accelerated release of the loaded DOX was realized in the presence of an elevated GSH that simulate the acidic endosomal compartments. PMID:25109617

  12. 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

  13. PEGylated and poloxamer-modified chitosan nanoparticles incorporating a lysine-based surfactant for pH-triggered doxorubicin release.

    PubMed

    Scheeren, Laís E; Nogueira, Daniele R; Macedo, Letícia B; Vinardell, M Pilar; Mitjans, Montserrat; Infante, M Rosa; Rolim, Clarice M B

    2016-02-01

    The growing demand for efficient chemotherapy in many cancers requires novel approaches in target-delivery technologies. Nanomaterials with pH-responsive behavior appear to have potential ability to selectively release the encapsulated molecules by sensing the acidic tumor microenvironment or the low pH found in endosomes. Likewise, polyethylene glycol (PEG)- and poloxamer-modified nanocarriers have been gaining attention regarding their potential to improve the effectiveness of cancer therapy. In this context, DOX-loaded pH-responsive nanoparticles (NPs) modified with PEG or poloxamer were prepared and the effects of these modifiers were evaluated on the overall characteristics of these nanostructures. Chitosan and tripolyphosphate were selected to form NPs by the interaction of oppositely charged compounds. A pH-sensitive lysine-based amphiphile (77KS) was used as a bioactive adjuvant. The strong dependence of 77KS ionization with pH makes this compound an interesting candidate to be used for the design of pH-sensitive devices. The physicochemical characterization of all NPs has been performed, and it was shown that the presence of 77KS clearly promotes a pH-triggered DOX release. Accelerated and continuous release patterns of DOX from CS-NPs under acidic conditions were observed regardless of the presence of PEG or poloxamer. Moreover, photodegradation studies have indicated that the lyophilization of NPs improved DOX stability under UVA radiation. Finally, cytotoxicity experiments have shown the ability of DOX-loaded CS-NPs to kill HeLa tumor cells. Hence, the overall results suggest that these pH-responsive CS-NPs are highly potent delivery systems to target tumor and intracellular environments, rendering them promising DOX carrier systems for cancer therapy. PMID:26674840

  14. Liver cancer cells: targeting and prolonged-release drug carriers consisting of mesoporous silica nanoparticles and alginate microspheres

    PubMed Central

    Liao, Yu-Te; Liu, Chia-Hung; Yu, Jiashing; Wu, Kevin C-W

    2014-01-01

    A new microsphere consisting of inorganic mesoporous silica nanoparticles (MSNs) and organic alginate (denoted as MSN@Alg) was successfully synthesized by air-dynamic atomization and applied to the intracellular drug delivery systems (DDS) of liver cancer cells with sustained release and specific targeting properties. MSN@Alg microspheres have the advantages of MSN and alginate, where MSN provides a large surface area for high drug loading and alginate provides excellent biocompatibility and COOH functionality for specific targeting. Rhodamine 6G was used as a model drug, and the sustained release behavior of the rhodamine 6G-loaded MSN@Alg microspheres can be prolonged up to 20 days. For targeting therapy, the anticancer drug doxorubicin was loaded into MSN@Alg microspheres, and the (lysine)4-tyrosine-arginine-glycine-aspartic acid (K4YRGD) peptide was functionalized onto the surface of MSN@Alg for targeting liver cancer cells, hepatocellular carcinoma (HepG2). The results of the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay and confocal laser scanning microscopy indicate that the MSN@Alg microspheres were successfully uptaken by HepG2 without apparent cytotoxicity. In addition, the intracellular drug delivery efficiency was greatly enhanced (ie, 3.5-fold) for the arginine-glycine-aspartic acid (RGD)-labeled, doxorubicin-loaded MSN@Alg drug delivery system compared with the non-RGD case. The synthesized MSN@Alg microspheres show great potential as drug vehicles with high biocompatibility, sustained release, and targeting features for future intracellular DDS. PMID:24940057

  15. Large intestine-targeted nanoparticle-releasing oral vaccine to control genitorectal viral infection

    PubMed Central

    Zhu, Qing; Talton, James; Zhang, Guofeng; Cunningham, Tshaka; Wang, Zijian; Waters, Robert C.; Kirk, James; Eppler, Bärbel; Dennis M, Klinman; Sui, Yongjun; Gagnon, Susan; Belyakov, Igor M.; Mumper, Russell J.; Berzofsky, Jay A.

    2012-01-01

    Both rectal and vaginal mucosal surfaces serve as transmission routes for pathogenic microorganisms. Vaccination through large intestinal mucosa, previously proven protective for both mucosal sites in animal studies, can be achieved successfully by direct intra-colorectal (i.c.r.) administration, which is, however, clinically impractical. Oral delivery seems preferable, but risks vaccine 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 or 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 novel strategy for immune protection of rectal and vaginal mucosa. PMID:22797811

  16. Advances in Peptide Functionalization on Mesoporous Silica Nanoparticles for Controlled Drug Release.

    PubMed

    Hu, Jing-Jing; Xiao, Dong; Zhang, Xian-Zheng

    2016-07-01

    During the last decade, using versatile, promising, and fascinating mesoporous silica nanoparticles (MSNs) as site-specific and stimuli-responsive drug delivery systems (DDSs) has received concentrated research interest. As one of the most attractive surface modification units, peptides have inherent bioactivity, biodegradability and biocompatibility. Recent progresses in the utilization of versatile peptides for surface functionalization of MSNs to achieve cell-specific targeting, fluorescence imaging, and intracellular diagnosis and treatment of tumors are summarized in this review. The various functional peptides decorated on the MSNs are introduced and classified into three types, including targeting peptides, stimuli-responsive peptides and multifunctional chimeric peptides. The limitations and challenges of peptide modified MSNs and their potential applications are further discussed. PMID:27152737

  17. Ultrasound-triggered dual-drug release from poly(lactic-co-glycolic acid)/mesoporous silica nanoparticles electrospun composite fibers

    PubMed Central

    Song, Botao; Wu, Chengtie; Chang, Jiang

    2015-01-01

    The aim of this study was to achieve on-demand controlled drug release from the dual-drug-loaded poly(lactic-co-glycolic acid)/mesoporous silica nanoparticles electrospun composite fibers by the application of ultrasound irradiation. Two drugs were loaded in different part of the composite fibrous materials, and it was found that ultrasound as an external stimulus was able to control release of drugs due to both its thermal effect and non-thermal effect. With the selective irradiation of ultrasound, the drug carrier enabled to realize controlled release, and because of different location in fibers and sensitivity of two different kinds of drugs to ultrasound irradiation, the release rate of two drugs was different. These results indicated that ultrasound irradiation was a facile method to realize the on-demand controlled release of two drugs from the electrospun fibers. PMID:26816645

  18. CS/PAA@TPGS/PLGA nanoparticles with intracellular pH-sensitive sequential release for delivering drug to the nucleus of MDR cells.

    PubMed

    Wang, Ying-Ying; Zhang, Dan-Dan; Kong, Yan-Yan; Shao, Luan-Luan; Zhang, Fen-Yi; Gao, Yu; Mu, Xu; Wang, Jie; Li, Hao-Fan; Yu, Shu-Qin; Xu, Qian

    2016-09-01

    Development of novel nano-drug delivery systems (NDDS) that can transport anticancer drugs into cell nuclei is still a highly desirable strategy for reversing multi-drug resistance (MDR) in cancer therapy. Herein, we designed and prepared a novel NDDS, designated S@L NPs, in which several smaller nanoparticles are contained within a larger nanoparticle. Our S@L NPs (CS/PAA/VP-16@TPGS/PLGA NPs) possess a structure in which smaller nanoparticles (Chitosan-Poly(acrylic acid) nanoparticles, CS/PAA NPs) containing the drug etoposide (VP-16) are loaded within a larger nanoparticle (Vitamin E d-a-tocopheryl polyethylene glycol 1000 succinate-modified poly(lactic-co-glycolic acid) nanoparticles, TPGS/PLGA NPs). The system utilizes intracellular pH gradients to achieve pH-sensitive sequential release within different intracellular domains of MDR cells. S@L NPs could be triggered to degrade and release CS/PAA/VP-16 NPs in the acid environment of the cytosol, endosomes or lysosomes, and CS/PAA/VP-16 NPs were capable of entering the nucleus through nucleopores. It is significant that CS/PAA/VP-16 NPs exhibit disaggregation in the alkaline environment of the nucleus and thereby release the contained anticancer drug. Further mechanistic studies showed that CS/PAA/VP-16 NPs escaped retention and degradation within lysosomes and protected the drug from P-glycoprotein-induced efflux. Simultaneously, S@L NPs enhanced the anticancer effect of the loaded drug by inducing autophagy and apoptosis of MDR cells. This novel NDDS may provide a promising platform for nuclear drug delivery for reversing MDR. PMID:27289313

  19. 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

  20. 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. PMID:26946013

  1. 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

  2. Biocompatible nanoparticles sensing the matrix metallo-proteinase 2 for the on-demand release of anticancer drugs in 3D tumor spheroids.

    PubMed

    Cantisani, Marco; Guarnieri, Daniela; Biondi, Marco; Belli, Valentina; Profeta, Martina; Raiola, Luca; Netti, Paolo A

    2015-11-01

    The balance between dose-dependent tolerability, effectiveness and toxicity of systemically administered antitumor drugs is extremely delicate. This issue highlights the striking need for targeted release of chemotherapeutic drugs within tumors. In this work, a smart strategy of drug targeting to tumors relying upon biodegradable/biocompatible nanoparticles releasing cytotoxic drugs after sensing physiological variations intrinsic to the very nature of tumor tissues is exploited. Here, the well-known over-expression of matrix metallo-proteinase 2 (MMP2) enzyme in tumors has been chosen as a trigger for the release of a cytotoxic drug. Nanoparticles made up of a biodegradable poly(D,L-lactic-co-glycolic acid) (PLGA)--block--polyethylene glycol (PEG) copolymer (namely PELGA), blended with a tumor-activated prodrug (TAP) composed of a MMP2-sensitive peptide bound to doxorubicin (Dox) and to PLGA chain have been produced. The obtained devices are able to release Dox specifically upon MMP2 cleavage of the TAP. More interestingly, they can sense the differences in the expression levels of endogenous MMP2 protein, thus modulating drug penetration within a three-dimensional (3D) tumor spheroid matrix, accordingly. Therefore, the proposed nanoparticles hold promise as a useful tool for in vivo investigations aimed at an improved therapeutic efficacy of the conjugated drug payload. PMID:26340360

  3. 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. PMID:22797811

  4. Comparative modeling of exposure to airborne nanoparticles released by consumer spray products.

    PubMed

    Riebeling, Christian; Luch, Andreas; Götz, Mario Enrico

    2016-04-01

    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. PMID:26418667

  5. 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

  6. 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

  7. 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

  8. Preparation and characterization of chitosan-Polyethylene glycol-polyvinylpyrrolidone-coated superparamagnetic iron oxide nanoparticles as carrier system: Drug loading and in vitro drug release study.

    PubMed

    Prabha, G; Raj, V

    2016-05-01

    In the present research work, the anticancer drug "curcumin" is loaded with Chitosan (CS)-polyethylene glycol (PEG)-polyvinylpyrrolidone (PVP) (CS-PEG-PVP) polymer nanocomposites coated with superparamagnetic iron oxide (Fe3 O4 ) nanoparticles. The system can be used for targeted and controlled drug delivery of anticancer drugs with reduced side effects and greater efficiency. The prepared nanoparticles were characterized by Fourier transmission infrared spectroscopy (FTIR), vibrating sample magnetometry (VSM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Curcumin drug-loaded Fe3 O4 -CS, Fe3 O4 -CS- PEG and Fe3 O4 -CS-PEG-PVP nanoparticles exhibited the mean particle size in the range of 183 - 390 nm with a zeta potential value of 26 mV-41 mV as measured using Malvern Zetasizer. The encapsulation efficiency, loading capacity and in-vitro drug release behaviour of curcumin drug-loaded Fe3 O4 -CS, Fe3 O4 -CS-PEG, and Fe3 O4 -CS-PEG-PVP nanoparticles were studied using UV spectrophotometer. Besides, the cytotoxicity of the prepared nanoparticles using MTT assay was also studied. The curcumin drug release was examined at different pH medium (4.5 and 7.4) and temperature (37°C and 45°C), and it was proved that the drug release depends upon the pH medium and temperature in addition to the nature of matrix. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 808-816, 2016. PMID:26996397

  9. Composite scaffolds for controlled drug release: role of the polyurethane nanoparticles on the physical properties and cell behaviour.

    PubMed

    Gentile, Piergiorgio; Bellucci, Devis; Sola, Antonella; Mattu, Clara; Cannillo, Valeria; Ciardelli, Gianluca

    2015-04-01

    Localised delivery of appropriate biomolecule/drug(s) can be suitable to prevent postoperative infections and inflammation after scaffold implantation in vivo. In this study composite shell scaffolds, based on an internally produced bioactive glass and a commercial hydroxyapatite, were surface coated with a uniform polymeric layer, embedded with thermo-stable polyesterurethane (PU)-based nanoparticles (NPs), containing an anti-inflammatory drug (indomethacin; IDCM). The obtained functionalised scaffolds were subjected to physico-mechanical and biological characterisations. The results indicated that NPs incorporation into the gelatin coating of the composite scaffolds: 1) not changed significantly the micro-architecture of the scaffolds in terms of mean pore diameter and pore size distribution; 2) increased the compressive modulus; and 3) allowed to a sustained IDMC release (65-70% of the loaded-drug) within the first week of incubation in physiological solution. On the other hand, the NPs incorporation did not affect the biocompatibility of composite scaffolds, as evidenced by viability and alkaline phosphatase (ALP) activity of MG63 human osteoblast-like cells. PMID:25617789

  10. Preparation of pH-responsive mesoporous hydroxyapatite nanoparticles for intracellular controlled release of an anticancer drug.

    PubMed

    Li, Dalong; Huang, Xin; Wu, Yadong; Li, Jiwei; Cheng, Weilu; He, Jinmei; Tian, Huayu; Huang, Yudong

    2016-02-01

    A well-defined core-shell nano-carrier (PAA-MHAPNs) was successfully synthesized based on a graft-onto method by using mesoporous hydroxyapatite nanoparticles (MHAPNs) as the core and polyacrylic acid (PAA) as the shell. Given that MHAPNs are regarded as one of the most promising drug delivery vehicles due to their excellent performance and the nature of their cancer cell anti-proliferative effect, and the grafted PAA, as a pH-responsive switch, could improve the loading amount of the drug doxorubicin hydrochloride (DOX) effectively by electrostatic interactions, all these advantages mean that the designed models show promise for application in pH-responsive drug delivery systems. The loading content and entrapment efficiency of DOX could reach up to 3.3% and 76%, respectively. The drug release levels of the constructed DOX@PAA-MHAPNs were low under normal physiological conditions (pH 7.4), but they could be increased significantly with a decrease of pH. Cytotoxicity assays indicated that the PAA-MHAPNs was biocompatible, and more importantly, the DOX@PAA-MHAPNs demonstrated an obvious ability to induce apoptosis of cancer cells. Overall, the synthesized systems should show great potential as drug nanovehicles with excellent biocompatibility, high drug loading, and pH-responsive features for future intracellular drug delivery. PMID:26484364

  11. Biofunctionalized polymer-lipid supported mesoporous silica nanoparticles for release of chemotherapeutics in multidrug resistant cancer cells.

    PubMed

    Zhang, Xinxin; Li, Feifei; Guo, Shiyan; Chen, Xi; Wang, Xiaoli; Li, Juan; Gan, Yong

    2014-04-01

    Multidrug resistance (MDR) is a major impediment to the success of cancer chemotherapy. A polymer-lipid supported mesoporous silica nanoparticle (PLS-MSNs) is described here to facilitate intracellular delivery of anticancer drug and enhance the antitumor efficacy against MDR breast cancer cells. By coating MSNs with a synthetic dual-functional polymer-lipid material P123-DOPE, the supported membrane acted as an intact barrier against the escape of encapsulated drugs before reaching the target cells, leading to depolymerization and triggered storm release of loaded irinotecan (CPT-11) in acidic endosomal pH of tumor cells. In addition, P123-DOPE can inhibit breast cancer resistance protein (BCPR) mediated CPT-11 efflux in drug resistant MCF-7/BCRP breast cancer cells, thus acting as a "door blocker". Compared to free CPT-11, PLS-MSNs resulted in a maximum increase in the intracellular CPT-11 concentration (12.9-fold), had 7.1-fold higher cytotoxicity and processed a stronger cell cycle arrest in MCF-7/BCRP cells. Moreover, CPT-11 loaded PLS-MSNs showed high therapeutic performance and low toxicity in BALB/c nude mice bearing drug resistant breast tumors, with an inhibition rate of 81.2% compared to free CPT-11 treatment group. The reported PLS-MSNs provide promising applicability in future preclinical and clinical MDR cancer treatment. PMID:24462359

  12. Synthesis of chitosan networks: Swelling, drug release, and magnetically assisted BSA separation using Fe3O4 nanoparticles.

    PubMed

    Ghaemy, Mousa; Naseri, Motahare

    2012-10-15

    Chitosan (CS) nanohydrogel networks were prepared by reaction with glyceroldiglycidylether (GDE) and poly(dimethylsiloxane) (PDMS), as crosslinking agents in an emulsion system. The nanogel content increased with increasing the amount of crosslinkers and reached to a maximum of 90% with GDE. The nanogels structure was characterized by FT-IR, AFM, DSC, and TGA. The average size for CS-GDE and CS-PDMS particles were 59nm and 180nm, respectively. The swelling behavior of nanohydrogels was observed to be dependent on pH, temperature, degree of crosslinking, and on the chemical structure of crosslinker. The equilibrium water content of CS-GDE nanohydrogels reached to a maximum of 600% at neutral pH, and decreased at high and low pH and low temperature. These nanohydrogels were tested for sodium diclofenac (SDF) loading and releasing efficiency. The covalent conjugation of bovine serum albumin (BSA) and magnetic Fe(3)O(4) nanoparticles on the hydrogels were found to hold a potential application in magnetically assisted bioseparation. PMID:22939340

  13. 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

  14. 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

  15. 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

  16. Redox-Triggered Release of Moxifloxacin from Mesoporous Silica Nanoparticles Functionalized with Disulfide Snap-Tops Enhances Efficacy Against Pneumonic Tularemia in Mice.

    PubMed

    Lee, Bai-Yu; Li, Zilu; Clemens, Daniel L; Dillon, Barbara Jane; Hwang, Angela A; Zink, Jeffrey I; Horwitz, Marcus A

    2016-07-01

    Effective and rapid treatment of tularemia is needed to reduce morbidity and mortality of this potentially fatal infectious disease. The etiologic agent, Francisella tularensis, is a facultative intracellular bacterial pathogen which infects and multiplies to high numbers in macrophages. Nanotherapeutics are particularly promising for treatment of infectious diseases caused by intracellular pathogens, whose primary host cells are macrophages, because nanoparticles preferentially target and are avidly internalized by macrophages. A mesoporous silica nanoparticle (MSN) has been developed functionalized with disulfide snap-tops that has high drug loading and selectively releases drug intracellularly in response to the redox potential. These nanoparticles, when loaded with Hoechst fluorescent dye, release their cargo exclusively intracellularly and stain the nuclei of macrophages. The MSNs loaded with moxifloxacin kill F. tularensis in macrophages in a dose-dependent fashion. In a mouse model of lethal pneumonic tularemia, MSNs loaded with moxifloxacin prevent weight loss, illness, and death, markedly reduce the burden of F. tularensis in the lung, liver, and spleen, and are significantly more efficacious than an equivalent amount of free drug. An important proof-of-principle for the potential therapeutic use of a novel nanoparticle drug delivery platform for the treatment of infectious diseases is provided. PMID:27246117

  17. DNA-capped mesoporous silica nanoparticles as an ion-responsive release system to determine the presence of mercury in aqueous solutions

    PubMed Central

    Zhang, Yunfei; Yuan, Quan; Chen, Tao; Chen, Yan

    2013-01-01

    We have developed DNA-functionalized silica nanoparticles for the rapid, sensitive, and selective detection of mercuric ion (Hg2+) in aqueous solution. Two DNA strands were designed to cap the pore of dye-trapped silica nanoparticles. In the presence of ppb level Hg2+, the two DNA strands are dehybridized to uncap the pore, releasing the dye cargo with detectable enhancements of fluorescence signal. This method enables rapid (less than 20min) and sensitive (LOD 4ppb) detection, and it was also able to discriminate Hg2+ from twelve other environmentally relevant metal ions. The superior properties of the as-designed DNA-functionalized silica nanoparticles can be attributed to the large loading capacity and highly ordered pore structure of mesoporous silica nanoparticles, as well as the selective binding of thymine-rich DNA with Hg2+ . 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:22240146

  18. 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

  19. Effects of hydrophobic drug polyesteric core interactions on drug loading and release properties of poly(ethylene glycol) polyester poly(ethylene glycol) triblock core shell nanoparticles

    NASA Astrophysics Data System (ADS)

    Khoee, Sepideh; Hassanzadeh, Salman; Goliaie, Bahram

    2007-05-01

    BAB amphiphilic triblock copolymers consisting of poly(ethylene glycol) (B) (PEG) as the hydrophilic segment and different polyesters (A) as the hydrophobic block were prepared by a polycondensation reaction as efficient model core-shell nanoparticles to assay the effect of interactions between the hydrophobic drug and the polyesteric core in terms of drug loading content and release profile. PEG-poly(hexylene adipate)-PEG (PEG-PHA-PEG) and PEG-poly(butylene adipate)-PEG (PEG-PBA-PEG) to PEG-poly(ethylene adipate)-PEG (PEG-PEA-PEG) core-shell type nanoparticles entrapping quercetin (an anticarcinogenic, allergy inhibitor and antibacterial agent), were prepared by a nanoprecipitation method and characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM) and x-ray diffraction (XRD) techniques. It was found that the obtained nanoparticles showed a smooth surface and spherical shape with controllable sizes in the range of 64-74 nm, while drug loading varied from 7.24% to 19% depending on the copolymer composition and the preparation conditions. The in vitro release behaviour exhibited a sustained release and was affected by the polymer-drug interactions. UV studies revealed the presence of hydrogen bonding as the main existing interaction between quercetin and polyesters in the nanosphere cores.

  20. 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

  1. Design of sustained release fine particles using two-step mechanical powder processing: particle shape modification of drug crystals and dry particle coating with polymer nanoparticle agglomerate.

    PubMed

    Kondo, Keita; Ito, Natsuki; Niwa, Toshiyuki; Danjo, Kazumi

    2013-09-10

    We attempted to prepare sustained release fine particles using a two-step mechanical powder processing method; particle-shape modification and dry particle coating. First, particle shape of bulk drug was modified by mechanical treatment to yield drug crystals suitable for the coating process. Drug crystals became more rounded with increasing rotation speed, which demonstrates that powerful mechanical stress yields spherical drug crystals with narrow size distribution. This process is the result of destruction, granulation and refinement of drug crystals. Second, the modified drug particles and polymer coating powder were mechanically treated to prepare composite particles. Polymer nanoparticle agglomerate obtained by drying poly(meth)acrylate aqueous dispersion was used as a coating powder. The porous nanoparticle agglomerate has superior coating performance, because it is completely deagglomerated under mechanical stress to form fine fragments that act as guest particles. As a result, spherical drug crystals treated with porous agglomerate were effectively coated by poly(meth)acrylate powder, showing sustained release after curing. From these findings, particle-shape modification of drug crystals and dry particle coating with nanoparticle agglomerate using a mechanical powder processor is expected as an innovative technique for preparing controlled-release coated particles having high drug content and size smaller than 100 μm. PMID:23796831

  2. Light-responsive nanoparticle depot to control release of a small molecule angiogenesis inhibitor in the posterior segment of the eye.

    PubMed

    Huu, Viet Anh Nguyen; 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

    2015-02-28

    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

  3. Characterization of Colloidal Nanoparticles Released from Hg-bearing Mine Wastes

    NASA Astrophysics Data System (ADS)

    Shaw, S.; Lowery, G. V.; Kim, C.; Rytuba, J. J.; Brown, G. E.

    2001-12-01

    The release of mercury from mine waste tailings at historic mining sites in the California coastal ranges is a significant pollution threat to local water sources and fish populations. The transport of mercury associated with nanometer-scale (¯50-400 nm) colloidal particles is one of the major pathways for mercury release from these mine sites. This study has used laboratory column ex-periments to generate colloids from calcines and unprocessed waste rock from the New Idria (NI) and Sulphur Bank (SB) mines. Colloid generation was initiated by flowing two solutions of vary-ing ionic strength through the columns in the presence of malonic acid. The colloidal material generated was characterized by ATEM, Extend X-ray absorption fine structure (EXAFS) analysis, and chemical sequential extraction techniques. ATEM analysis indicates that the colloids generated from the NI calcines consist of crystalline alunite-jarosite and hematite, a poorly ordered Si-Al gel and HgS. This mixture is very similar to that present in the bulk calcine material and suggests that these colloids are formed by detach-ment/breakup of the bulk material. Hg-LIII-EXAFS and sequential extractions indicate that 90% of the mercury present in these colloids is in the HgS form. The column experiments on the SB calcines produced only a small amount of colloidal material when the first few pore volumes of solution were flowed through. These consist of quartz, poorly ordered Si-Al-Fe gel and HgS. Hg-LIII-EXAFS spectra confirms that HgS is the dominant mercury species in these colloids. Raising the pH of the colloid-free column effluent from the SB calcines experiment results in the precipita-tion of a poorly ordered Si-Al-Fe rich gel, which is similar to that observed at the waste pile/lake interface next to the SB mine (Clear lake, CA). EXAFS and ATEM results indicate that mercury can be associated with this precipitated colloidal material. Colloids generated using unprocessed waste rock from the SB

  4. Gravity spun polycaprolactone fibres: controlling release of a hydrophilic macromolecule (ovalbumin) and a lipophilic drug (progesterone).

    PubMed

    Williamson, Matthew R; Chang, Hsin-I; Coombes, Allan G A

    2004-09-01

    A hydrophilic macromolecule (ovalbumin (OVA)) and a lipophilic drug (progesterone) were incorporated in polycaprolactone (PCL) fibres by gravity spinning using particulate dispersions and co-solutions of PCL and steroid, respectively. PCL fibres loaded with 1% (w/w) OVA powder displayed a pronounced burst release phase (60% of the protein load) over 2 days in PBS at 37 degrees C. The release profile then tended to plateau. In contrast, OVA nanoparticle-loaded fibres exhibited delayed protein release initially and then a major increase at day 14. This behaviour may be useful for sequential release of polypeptide growth factors which are influential at specific time points in the wound healing process. SDS-PAGE analysis revealed that the protein molecular weight was conserved during fibre spinning. The amount of progesterone release from PCL fibres in PBS increased with drug loading but the cumulative release profiles (% w/w) were little affected by the initial drug loading of the fibres (1.5 and 3.5% w/w) or the concentration of the PCL spinning solution (12.5 and 20% w/v). Steroid delivery was rapid due to the high fibre surface area and high permeability of PCL resulting in complete drug loss over 24h. Released progesterone inhibited the growth of MCF-7 breast epithelial cells in culture, demonstrating retention of bioactivity. Gravity spinning shows potential for producing PCL fibre-based platforms for programmed delivery of bioactive molecules of utility for tissue engineering and drug delivery. PMID:15109868

  5. 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.

  6. Sequential co-delivery of miR-21 inhibitor followed by burst release doxorubicin using NIR-responsive hollow gold nanoparticle to enhance anticancer efficacy.

    PubMed

    Ren, Yu; Wang, Ruirui; Gao, Lizhang; Li, Ke; Zhou, Xuan; Guo, Hua; Liu, Chaoyong; Han, Donglin; Tian, Jianguo; Ye, Qing; Hu, Ye Tony; Sun, Duxin; Yuan, Xubo; Zhang, Ning

    2016-04-28

    Previous literature and our study showed the delivery sequence of microRNA inhibitor and chemotherapeutic compounds achieve distinct therapeutic anticancer efficacy. Yet, it is challenging to use nanoparticle to achieve sequential drug delivery. In the current study, we designed sequential co-delivery system using a near-infrared-radiation (NIR) responsive hollow gold nanoparticle (HGNPs) to achieve sequential release of microRNA inhibitor (miR-21i)/doxirubicin(Dox) in order to achieve synergistic efficacy. PAMAM modified HGNPs was used to encapsulate miR-21i and Dox. Upon entering tumor cells, miRNA-21i was released first to sensitize the cancer cells, the subsequent burst release of Dox was achieved by NIR triggered collapse of HGNPs. This sequential delivery of miRNA-21i and Dox produced a synergistic apoptotic response, thereby enhancing anticancer efficacy by 8-fold and increasing anti-cancer stem cell activity by 50-fold. The sequential delivery of miR-21i and Dox using HGNPs under NIR after intravenous administration showed high tumor accumulation and significantly improved efficacy, which was 4-fold compared to free Dox group. These data suggested that the sequential co-delivery of miR-21i followed by burst release Dox using NIR-responsive HGNPs sensitized cancer cells to chemotherapeutic compound, which provided a novel concept for co-delivery miRNA inhibitors and chemotherapeutic compounds to enhance their efficacy. PMID:26956593

  7. Gold nanoparticles interacting with β-cyclodextrin-phenylethylamine inclusion complex: a ternary system for photothermal drug release.

    PubMed

    Sierpe, Rodrigo; Lang, Erika; Jara, Paul; Guerrero, Ariel R; Chornik, Boris; Kogan, Marcelo J; Yutronic, Nicolás

    2015-07-22

    We report the synthesis of a 1:1 β-cyclodextrin-phenylethylamine (βCD-PhEA) inclusion complex (IC) and the adhesion of gold nanoparticles (AuNPs) onto microcrystals of this complex, which forms a ternary system. The formation of the IC was confirmed by powder X-ray diffraction and NMR analyses ((1)H and ROESY). The stability constant of the IC (760 M(-1)) was determined using the phase solubility method. The adhesion of AuNPs was obtained using the magnetron sputtering technique, and the presence of AuNPs was confirmed using UV-vis spectroscopy (surface plasmon resonance effect), which showed an absorbance at 533 nm. The powder X-ray diffractograms of βCD-PhEA were similar to those of the crystals decorated with AuNPs. A comparison of the one- and two-dimensional NMR spectra of the IC with and without AuNPs suggests partial displacement of the guest to the outside of the βCD due to attraction toward AuNPs, a characteristic tropism effect. The size, morphology, and distribution of the AuNPs were analyzed using TEM and SEM. The average size of the AuNPs was 14 nm. Changes in the IR and Raman spectra were attributed to the formation of the complex and to the specific interactions of this group with the AuNPs. Laser irradiation assays show that the ternary system βCD-PhEA-AuNPs in solution enables the release of the guest. PMID:26091143

  8. 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

  9. 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.

  10. Core-Shell Soy Protein-Soy Polysaccharide Complex (Nano)particles as Carriers for Improved Stability and Sustained Release of Curcumin.

    PubMed

    Chen, Fei-Ping; Ou, Shi-Yi; Tang, Chuan-He

    2016-06-22

    Using soy protein isolate (SPI) and soy-soluble polysaccharides (SSPS) as polymer matrixes, this study reported a novel process to fabricate unique core-shell complex (nano)particles to perform as carriers for curcumin (a typical poorly soluble bioactive). In the process, curcumin-SPI nanocomplexes were first formed at pH 7.0 and then coated by SSPS. At this pH, the core-shell complex was formed in a way the SPI nanoparticles might be incorporated into the interior of SSPS molecules without distinctly affecting the size and morphology of particles. The core-shell structure was distinctly changed by adjusting pH from 7.0 to 4.0. At pH 4.0, SSPS was strongly bound to the surface of highly aggregated SPI nanoparticles, and as a consequence, much larger complexes were formed. The bioaccessibility of curcumin in the SPI-curcumin complexes was unaffected by the SSPS coating. However, the core-shell complex formation greatly improved the thermal stability and controlled release properties of encapsulated curcumin. The improvement was much better at pH 4.0 than that at pH 7.0. All of the freeze-dried core-shell complex preparations exhibited good redispersion behavior. The findings provide a simple approach to fabricate food-grade delivery systems for improved water dispersion, heat stability, and even controlled release of poorly soluble bioactives. PMID:27243766

  11. Aptamer/Graphene Quantum Dots Nanocomposite Capped Fluorescent Mesoporous Silica Nanoparticles for Intracellular Drug Delivery and Real-Time Monitoring of Drug Release.

    PubMed

    Zheng, Fen-Fen; Zhang, Peng-Hui; Xi, Yu; Chen, Jing-Jia; Li, Ling-Ling; Zhu, Jun-Jie

    2015-12-01

    Great challenges in investigating the release of drug in complex cellular microenvironments necessitate the development of stimuli-responsive drug delivery systems with real-time monitoring capability. In this work, a smart drug nanocarrier based on fluorescence resonance energy transfer (FRET) is fabricated by capping graphene quantum dots (GQDs, the acceptor) onto fluorescent mesoporous silica nanoparticles (FMSNs, the donor) via ATP aptamer for real-time monitoring of ATP-triggered drug release. Under extracellular conditions, the fluorescence of FMSNs remains in the "off" state in the low ATP level which is unable to trigger the release of drug. Once specifically recognized and internalized into the target tumor cells by AS1411 aptamer, in the ATP-rich cytoplasm, the conformation switch of the ATP aptamer causes the shedding of the GQDs from the nanocarriers, leading to the release of the loaded drugs and consequently severe cytotoxicity. Simultaneously, the fluorescence of FMSNs turns "on" along with the dissociation of GQDs, which allows real-time monitoring of the release of drug from the pores. Such a drug delivery system features high specificity of dual-target recognition with AS1411 and ATP aptamer as well as high sensitivity of the FRET-based monitoring strategy. Thus, the proposed multifunctional ATP triggered FRET-nanocarriers will find potential applications for versatile drug-release monitoring, efficient drug transport, and targeted cancer therapeutics. PMID:26524192

  12. 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

  13. 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. PMID:23650272

  14. 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. PMID:25456989

  15. 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

  16. 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

  17. Design of magnetic molecularly imprinted polymer nanoparticles for controlled release of doxorubicin under an alternative magnetic field in athermal conditions.

    PubMed

    Griffete, N; Fresnais, J; Espinosa, A; Wilhelm, C; Bée, A; Ménager, C

    2015-12-01

    An innovative magnetic delivery nanomaterial for triggered cancer therapy showing active control over drug release by using an alternative magnetic field is proposed. In vitro and In vivo release of doxorubicin (DOX) were investigated and showed a massive DOX release under an alternative magnetic field without temperature elevation of the medium. PMID:26515533

  18. 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.

  19. Self-Assembled Nanoparticles Based on Amphiphilic Anticancer Drug-Phospholipid Complex for Targeted Drug Delivery and Intracellular Dual-Controlled Release.

    PubMed

    Li, Yang; Lin, Jinyan; Yang, Xiangrui; Li, Yanxiu; Wu, Shichao; Huang, Yu; Ye, Shefang; Xie, Liya; Dai, Lizong; Hou, Zhenqing

    2015-08-19

    Integrating advantages of mitomycin C (MMC)-phospholipid complex for increased drug encapsulation efficiency and reduced premature drug release, DSPE-PEG-folate (DSPE-PEG-FA) for specific tumor targeting, we reported a simple one-pot self-assembly route to prepare the MMC-phospholipid complex-loaded DSPE-PEG-based nanoparticles (MP-PEG-FA NPs). Both confocal imaging and flow cytometry demonstrated that MMC was distributed into nuclei after cellular uptake and intracellular drug delivery. More importantly, the systemically administered MP-PEG-FA NPs led to increased blood persistence and enhanced tumor accumulation in HeLa tumor-bearing nude mice. This study introduces a simple and effective strategy to design the anticancer drug-phospholipid complex-based targeted drug delivery system for sustained/controlled drug release. PMID:26234408

  20. Biosensor based on ultrasmall MoS2 nanoparticles for electrochemical detection of H2O2 released by cells at the nanomolar level.

    PubMed

    Wang, Tanyuan; Zhu, Haichuan; Zhuo, Junqiao; Zhu, Zhiwei; Papakonstantinou, Pagona; Lubarsky, Gennady; Lin, Jian; Li, Meixian

    2013-11-01

    Monodispersed surfactant-free MoS2 nanoparticles with sizes of less than 2 nm were prepared from bulk MoS2 by simple ultrasonication and gradient centrifugation. The ultrasmall MoS2 nanoparticles expose a large fraction of edge sites, along with their high surface area, which lead to attractive electrocatalytic activity for reduction of H2O2. An extremely sensitive H2O2 biosensor based on MoS2 nanoparticles with a real determination limit as low as 2.5 nM and wide linear range of 5 orders of magnitude was constructed. On the basis of this biosensor, the trace amount of H2O2 released from Raw 264.7 cells was successfully recorded, and an efficient glucose biosensor was also fabricated. Since H2O2 is a byproduct of many oxidative biological reactions, this work serves as a pathway for the application of MoS2 in the fields of electrochemical sensing and bioanalysis. PMID:24067077

  1. Zinc Oxide Nanoparticles as Adjuvant To Facilitate Doxorubicin Intracellular Accumulation and Visualize pH-Responsive Release for Overcoming Drug Resistance.

    PubMed

    Liu, Juan; Ma, Xiaowei; Jin, Shubin; Xue, Xiangdong; Zhang, Chunqiu; Wei, Tuo; Guo, Weisheng; Liang, Xing-Jie

    2016-05-01

    Multidrug resistance (MDR) of cancer is a challenge to effective chemotherapeutic interventions. The stimulus-responsive drug delivery system (DDS) based on nanotechnology provides a promising approach to overcome MDR. Through the development of a doxorubicin delivery system based on zinc oxide nanomaterials, we have demonstrated that MDR in breast cancer cell line can be significantly circumvented by a combination of efficient cellular uptake and a pH-triggered rapid drug release due to degradation of nanocarriers in acidic environment. Doxorubicin and zinc oxide nanoparticles, compared with free doxorubicin, effectively enhanced the intracellular drug concentration by simultaneously increasing cell uptake and decreasing cell efflux in MDR cancer cells. The acidic environment-triggered release of drug can be tracked real-time by the doxorubicin fluorescence recovery from its quenched state. Therefore, with the combination of therapeutic potential and the capacity to track release of drug in cancer cells, our system holds great potential in nanomedicine by serving dual roles of overcoming drug resistance and tracking intracellular drug release from the DDS. PMID:27070828

  2. 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

  3. Design of magnetic molecularly imprinted polymer nanoparticles for controlled release of doxorubicin under an alternative magnetic field in athermal conditions

    NASA Astrophysics Data System (ADS)

    Griffete, N.; Fresnais, J.; Espinosa, A.; Wilhelm, C.; Bée, A.; Ménager, C.

    2015-11-01

    An innovative magnetic delivery nanomaterial for triggered cancer therapy showing active control over drug release by using an alternative magnetic field is proposed. In vitro and In vivo release of doxorubicin (DOX) were investigated and showed a massive DOX release under an alternative magnetic field without temperature elevation of the medium.An innovative magnetic delivery nanomaterial for triggered cancer therapy showing active control over drug release by using an alternative magnetic field is proposed. In vitro and In vivo release of doxorubicin (DOX) were investigated and showed a massive DOX release under an alternative magnetic field without temperature elevation of the medium. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06133d

  4. Sunlight-Triggered Nanoparticle Synergy: Teamwork of Reactive Oxygen Species and Nitric Oxide Released from Mesoporous Organosilica with Advanced Antibacterial Activity.

    PubMed

    Gehring, Julia; Trepka, Bastian; Klinkenberg, Nele; Bronner, Hannah; Schleheck, David; Polarz, Sebastian

    2016-03-01

    Colonization of surfaces by microorganisms is an urging problem. In combination with the increasing antibiotic resistance of pathogenic bacteria, severe infections are reported more frequently in medical settings. Therefore, there is a large demand to explore innovative surface coatings that provide intrinsic and highly effective antibacterial activity. Materials containing silver nanoparticles have been developed in the past for this purpose, but this solution has come into criticism due to various disadvantages like notable toxicity against higher organisms, the high price, and low abundance of silver. Here, we introduce a new, sunlight-mediated organosilica nanoparticle (NP) system based on silver-free antibacterial activity. The simultaneous release of nitric oxide (NO) in combination with singlet oxygen and superoxide radicals (O2(•-)) as reactive oxygen species (ROS) leads to the emergence of highly reactive peroxynitrite molecules with significantly enhanced biocidal activity. This special cooperative effect can only be realized, if the ROS-producing moieties and the functional entities releasing NO are spatially separated from each other. In one type of particle, Rose Bengal as an efficient singlet oxygen ((1)O2) producer was covalently bound to SH functionalities applying thiol-ene click chemistry. "Charging" the second type of particles with NO was realized by quantitatively transferring the thiol groups into S-nitrosothiol functionalities. We probed the oxidation power of ROS-NP alone and in combination with NO-NP using sunlight as a trigger. The high antibacterial efficiency of dual-action nanoparticles was demonstrated using disinfection assays with the pathogenic bacterium Pseudomonas aeruginosa. PMID:26883897

  5. Phase Composition Control of Calcium Phosphate Nanoparticles for Tunable Drug Delivery Kinetics and Treatment of Osteomyelitis. Part 1: Preparation and Drug Release

    PubMed Central

    Uskoković, Vuk; Desai, Tejal A.

    2012-01-01

    Developed in this study is a multifunctional material for simultaneous osseoinduction and drug delivery, potentially applicable in the treatment of osteomyelitis. It is composed of agglomerates of nanoparticles of calcium phosphate (CAP) with different monophasic contents. The drug loading capacity and the release kinetics were investigated on two model drug compounds with different chemical structures, sizes and adsorption propensities: bovine serum albumin and fluorescein. Loading of CAP powders with small molecule drugs was achieved by physisorption and desiccation-induced agglomeration of nanoparticulate subunits into microscopic blocks. The material dissolution rate and the drug release rate depended on the nature of the CAP phase, decreasing from monocalcium phosphate to monetite to amorphous CAP and calcium pyrophosphate to hydroxyapatite. The sustained release of the two model drugs was shown to be directly relatable to the degradation rate of CAP carriers. It was demonstrated that the degradation rate of the carrier and the drug release kinetics could be made tunable within the time scale of 1–2 h for the most soluble CAP phase, monocalcium phosphate, to 1–2 years for the least soluble one, hydroxyapatite. From the standpoint of antibiotic therapy for osteomyelitis, typically lasting for six weeks, the most prospective CAP powder was amorphous CAP with its release time scale for a small organic molecule, the same category to which antibiotics belong, of 1 – 2 months under the conditions applied in our experiments. By combining these different CAP phases in various proportions, drug release profiles could be tailored to the therapeutic occasion. PMID:23115118

  6. Phase composition control of calcium phosphate nanoparticles for tunable drug delivery kinetics and treatment of osteomyelitis. I. Preparation and drug release.

    PubMed

    Uskoković, Vuk; Desai, Tejal A

    2013-05-01

    Developed in this study is a multifunctional material for simultaneous osseoinduction and drug delivery, potentially applicable in the treatment of osteomyelitis. It is composed of agglomerates of nanoparticles of calcium phosphate (CAP) with different monophasic contents. The drug-loading capacity and the release kinetics were investigated on two model drug compounds with different chemical structures, sizes, and adsorption propensities: bovine serum albumin and fluorescein. Loading of CAP powders with small molecule drugs was achieved by physisorption and desiccation-induced agglomeration of nanoparticulate subunits into microscopic blocks. The material dissolution rate and the drug release rate depended on the nature of the CAP phase, decreasing from monocalcium phosphate to monetite to amorphous CAP and calcium pyrophosphate to hydroxyapatite. The sustained release of the two model drugs was shown to be directly relatable to the degradation rate of CAP carriers. It was demonstrated that the degradation rate of the carrier and the drug release kinetics could be made tunable within the time scale of 1-2 h for the most soluble CAP phase, monocalcium phosphate, to 1-2 years for the least soluble one, hydroxyapatite. From the standpoint of antibiotic therapy for osteomyelitis, typically lasting for 6 weeks, the most prospective CAP powder was amorphous CAP with its release time scale for a small organic molecule, the same category to which antibiotics belong, of 1-2 months under the conditions applied in our experiments. By combining these different CAP phases in various proportions, drug release profiles could be tailored to the therapeutic occasion. PMID:23115118

  7. 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. PMID:24347375

  8. 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

  9. 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

  10. 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

  11. 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...

  12. Fluorescence turn-on detection of glucose via the Ag nanoparticle mediated release of a perylene probe.

    PubMed

    Li, Juanmin; Li, Yongxin; Shahzad, Sohail Anjum; Chen, Jian; Chen, Yang; Wang, Yan; Yang, Meiding; Yu, Cong

    2015-04-14

    A novel fluorescence turn-on strategy for glucose sensing is demonstrated. The fluorescence of a perylene probe could be quenched by the silver nanoparticles (Ag NPs). The Ag NPs could be etched by H2O2 generated from the enzymatic oxidation of glucose. And efficient probe fluorescence recovery was detected. PMID:25763414

  13. In vitro release and in vitro–in vivo correlation for silybin meglumine incorporated into hollow-type mesoporous silica nanoparticles

    PubMed Central

    Cao, Xia; Deng, Wen-Wen; Fu, Min; Wang, Liang; Tong, Shan-Shan; Wei, Ya-Wei; Xu, Ying; Su, Wei-Yan; Xu, Xi-ming; Yu, Jiang-Nan

    2012-01-01

    Background The purpose of this study was to develop a sustained drug-release model for water-soluble drugs using silica nanoparticles. Methods Hollow-type mesoporous silica nanoparticles (HMSNs) were prepared using Na2CO3 solution as the dissolution medium for the first time. The water-soluble compound, silybin meglumine, was used as the model drug. The Wagner–Nelson method was used to calculate the in vivo absorption fraction. Results The results of transmission electron microscopy and nitrogen adsorption revealed that the empty HMSNs had uniformly distributed particles of size 50–100 nm, a spherical appearance, a large specific surface area (385.89 ± 1.12 m2/g), and ultralow mean pore size (2.74 nm). The highly porous structure allowed a large drug-loading rate (58.91% ± 0.39%). In 0.08 M Na2CO3 solution, silybin meglumine-loaded HMSNs could achieve highly efficacious and long-term sustained release for 72 hours in vitro. The results of in vitro–in vivo correlation revealed that HMSNs in 0.08 M Na2CO3 solution had a correlation coefficient R2 value of 0.9931, while those of artificial gastric juice and artificial intestinal juice were only 0.9287 and 0.7689, respectively. Conclusion The findings of in vitro–in vivo correlation indicate that HMSNs together with Na2CO3 solution could achieve an excellent linear relationship between in vitro dissolution and in vivo absorption for 72 hours, leading to a promising model for sustained release of water-soluble drugs. PMID:22393284

  14. Alizarin Complexone Functionalized Mesoporous Silica Nanoparticles: A Smart System Integrating Glucose-Responsive Double-Drugs Release and Real-Time Monitoring Capabilities.

    PubMed

    Zou, Zhen; He, Dinggeng; Cai, Linli; He, Xiaoxiao; Wang, Kemin; Yang, Xue; Li, Liling; Li, Siqi; Su, Xiaoya

    2016-04-01

    The outstanding progress of nanoparticles-based delivery systems capable of releasing hypoglycemic drugs in response to glucose has dramatically changed the outlook of diabetes management. However, the developed glucose-responsive systems have not offered real-time monitoring capabilities for accurate quantifying hypoglycemic drugs released. In this study, we present a multifunctional delivery system that integrates both delivery and monitoring issues using glucose-triggered competitive binding scheme on alizarin complexone (ALC) functionalized mesoporous silica nanoparticles (MSN). In this system, ALC is modified on the surface of MSN as the signal reporter. Gluconated insulin (G-Ins) is then introduced onto MSN-ALC via benzene-1,4-diboronic acid (BA) mediated esterification reaction, where G-Ins not only blocks drugs inside the mesopores but also works as a hypoglycemic drug. In the absence of glucose, the sandwich-type boronate ester structure formed by BA binding to the diols of ALC and G-Ins remains intact, resulting in an fluorescence emission peak at 570 nm and blockage of pores. Following a competitive binding, the presence of glucose cause the dissociation of boronate ester between ALC and BA, which lead to the pores opening and disappearance of fluorescence. As proof of concept, rosiglitazone maleate (RSM), an insulin-sensitizing agent, was doped into the MSN to form a multifunctional MSN (RSM@MSN-ALC-BA-Ins), integrating with double-drugs loading, glucose-responsive performance, and real-time monitoring capability. It has been demonstrated that the glucose-responsive release behaviors of insulin and RSM in buffer or in human serum can be quantified in real-time through evaluating the changes of fluorescence signal. We believe that this developed multifunctional system can shed light on the invention of a new generation of smart nanoformulations for optical diagnosis, individualized treatment, and noninvasive monitoring of diabetes management. PMID

  15. Silver nanoparticles rapidly induce atypical human neutrophil cell death by a process involving inflammatory caspases and reactive oxygen species and induce neutrophil extracellular traps release upon cell adhesion.

    PubMed

    Liz, Rafael; Simard, Jean-Christophe; Leonardi, Laurien Bruna Araújo; Girard, Denis

    2015-09-01

    Inflammation is one of the major toxic effects reported in response to in vitro or in vivo nanoparticle (NP) exposure. Among engineered NPs, silver nanoparticles (AgNPs) are very attractive for the development of therapeutic strategies, especially because of their antimicrobial properties. In humans, neutrophils, key players in inflammation, are the most abundant blood leukocytes that spontaneously undergo apoptosis, a central cell death mechanism regulating inflammation. The aim of this study was to evaluate the effect of AgNPs on neutrophil apoptosis. Transmission electronic microscopy reveals that AgNPs rapidly penetrate inside neutrophils. AgNPs induced atypical cell death where the cell volume increased and the cell surface expression of CD16 remained unaltered unlike apoptotic neutrophils where cell shrinkage and loss of CD16 are typically observed. The AgNP-induced atypical cell death is distinct from necrosis and reversed by a pancaspase inhibitor or by inhibitors of the inflammatory caspase-1 and caspase-4. In addition, AgNPs induced IL-1β production inhibited by caspase-1 and caspase-4 inhibitors and also induced caspase-1 activity. Reactive oxygen species (ROS) production was increased by AgNPs and the atypical cell death was inhibited by the antioxidant n-acetylcysteine. Under similar experimental conditions, adhesion of neutrophils leads to neutrophil extracellular trap (NET) release induced by AgNPs. However, this process was not reversed by caspase inhibitors. We conclude that AgNPs rapidly induced an atypical cell death in neutrophils by a mechanism involving caspase-1, -4 and ROS. However, in adherent neutrophils, AgNPs induced NET release and, therefore, are novel agents able to trigger NET release. PMID:26241783

  16. Intracellular Delivery: Redox-Triggered Release of Moxifloxacin from Mesoporous Silica Nanoparticles Functionalized with Disulfide Snap-Tops Enhances Efficacy Against Pneumonic Tularemia in Mice (Small 27/2016).

    PubMed

    Lee, Bai-Yu; Li, Zilu; Clemens, Daniel L; Dillon, Barbara Jane; Hwang, Angela A; Zink, Jeffrey I; Horwitz, Marcus A

    2016-07-01

    The drug trapping and intracellular release mechanism of redox-responsive disulfide snap-top mesoporous silica nanoparticles (MSN-SS-MXF) is depicted by J. I. Zink, M. A. Horwitz and co-workers on page 3690. Mesoporous silica nanoparticles with antibiotic (cyan) trapped within their pores by disulfide snap-tops are avidly ingested by macrophages. The intracellular redox potential reduces the disulfide (yellow) in the stalk (green/blue), releases the caps (orange) and frees drug to kill Francisella tularensis (green). Artwork by Bastian Ruehle. PMID:27412305

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

    PubMed

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

    2016-01-15

    We fabricate a multifunctional nanocarrier based on multi-walled carbon nanotubes (MWCNTs) decorated with gold/silver core-shell nanoparticles (Au@Ag NPs) and fluorescein isothiocyanate (FITC) for tracking the intracellular drug release process. In the demonstrated nanocarrier, the Au@Ag NPs adsorbed on the surface of MWCNTs were labeled with the pH-dependent SERS reporter 4-Mercaptobenzoic acid (4MBA) for SERS based pH sensing. FITC was conjugated on MWCNTs to provide fluorescence signal for tracing the MWCNTs. Fluorescent doxorubicin (DOX) was used as the model drug which can be loaded onto MWCNTs via π-π stacking and released from the MWCNTs under acidic condition. By detecting the SERS spectrum of 4MBA, the pH value around the nanocarrier could be monitored. Besides, by tracing the fluorescence of FITC and DOX, we can also investigate the drug release process in cells. Experimental results show that the proposed nanocarrier retained a well pH-sensitive performance in living cells, and the DOX detached from MWCNTs inside the lysosomes and entered into the cytoplasm with the MWCNTs being left in lysosomes. To further investigate the drug release dynamics, 2-D color-gradient pH mapping were plotted, which were calculated from the SERS spectra of 4MBA. The detailed release process and carrier distribution have been recorded as environmental pH changes during cell endocytosis. Furthermore, we also confirmed that the proposed nanocarrier has a good biocompatibility. It indicates that the designed nanocarrier have a great potential in intraceable drug delivery, cancer cells imaging and pH monitoring. PMID:26360244

  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

    2015-08-01

    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

  19. 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

  20. Encapsulation of Alpha-1 antitrypsin in PLGA nanoparticles: In Vitro characterization as an effective aerosol formulation in pulmonary diseases

    PubMed Central

    2012-01-01

    Background Alpha 1- antitrypsin (α1AT) belongs to the superfamily of serpins and inhibits different proteases. α1AT protects the lung from cellular inflammatory enzymes. In the absence of α1AT, the degradation of lung tissue results to pulmonary complications. The pulmonary route is a potent noninvasive route for systemic and local delivery. The aerosolized α1AT not only affects locally its main site of action but also avoids remaining in circulation for a long period of time in peripheral blood. Poly (D, L lactide-co glycolide) (PLGA) is a biodegradable and biocompatible polymer approved for sustained controlled release of peptides and proteins. The aim of this work was to prepare a wide range of particle size as a carrier of protein-loaded nanoparticles to deposit in different parts of the respiratory system especially in the deep lung. Various lactide to glycolide ratio of the copolymer was used to obtain different release profile of the drug which covers extended and rapid drug release in one formulation. Results Nonaqueous and double emulsion techniques were applied for the synthesis of nanoparticles. Nanoparticles were characterized in terms of surface morphology, size distribution, powder X-ray diffraction (XRD), encapsulation efficiency, in vitro drug release, FTIR spectroscopy and differential scanning calorimetry (DSC). To evaluate the nanoparticles cytotoxicity, cell cytotoxicity test was carried out on the Cor L105 human epithelial lung cancer cell line. Nanoparticles were spherical with an average size in the range of 100 nm to 1μ. The encapsulation efficiency was found to be higher when the double emulsion technique was applied. XRD and DSC results indicated that α1AT encapsulated in the nanoparticles existed in an amorphous or disordered-crystalline status in the polymer matrix. The lactic acid to glycolic acid ratio affects the release profile of α1AT. Hence, PLGA with a 50:50 ratios exhibited the ability to release %60 of the drug within 8

  1. 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

  2. Development of novel core-shell dual-mesoporous silica nanoparticles for the production of high bioavailable controlled-release fenofibrate tablets.

    PubMed

    Zhao, Zongzhe; Gao, Yu; Wu, Chao; Hao, Yanna; Zhao, Ying; Xu, Jie

    2016-01-01

    Novel core-shell dual-mesoporous silica nanoparticles (DMSN) were successfully prepared as a carrier in order to improve the dissolution of fenofibrate and obtain an oral highly bioavailable controlled-release drug delivery system using the osmotic pump technology. Fenofibrate was loaded into DMSN by an adsorption method. The solid state properties of fenofibrate in DMSN, before and after drug loading, were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption/desorption analysis (BET), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC). In vitro release tests showed that DMSN increased the dissolution rate of fenofibrate and produced zero-order release in push-pull osmotic pump tablets (OPT). The relative bioavailability of OPT was 186.9% in comparison with the commercial reference product. In summary, osmotic pump technology in combination with solid dispersion technology involving nanometer materials is a promising way for achieving the oral delivery of poorly water-soluble drugs. PMID:26114553

  3. 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.

  4. Environmental pH-controlled loading and release of protein on mesoporous hydroxyapatite nanoparticles for bone tissue engineering.

    PubMed

    Zhang, Ning; Gao, Tianlin; Wang, Yu; Wang, Zongliang; Zhang, Peibiao; Liu, Jianguo

    2015-01-01

    To explore the controlled delivery of protein drugs in micro-environment established by osteoblasts or osteoclasts, the loading/release properties of bovine serum albumin (BSA) depending on pH environment were assessed. The adsorption amounts over mesoporous hydroxyapatite (MHA) or hydroxyapatite (HA) decreased as the pH increased, negatively correlating with zeta-potential values. The adsorption behavior over MHA fits well with the Freundlich and Langmuir models at different pHs. The results suggest that the adsorbed amount of protein on MHA or HA depended on the pH of protein solution. MHA adsorbed BSA at basic pH (MHApH 8.4) exhibited a different release kinetics compared with those in acid and neutral environments (MHApH 4.7 and MHApH 7.4), indicating that the release of protein could be regulated by environmental pH at which MHAs adsorb protein. MHApH 8.4 showed a sustained release for 6h before a gradual release when immersing in acidic environment, which is 2h longer than that in neutral environment. This suggests that MHApH 8.4 showed a more sustained release in acidic environment, which can be established by osteoclasts. The variation of adsorption strength between protein and MHA may be responsible for these behaviors. Our findings may be very useful for the development of MHA applications on both bone repair and protein delivery. PMID:25491972

  5. 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

  6. 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. PMID:25794580

  7. Loading of Silica Nanoparticles in Block Copolymer Vesicles during Polymerization-Induced Self-Assembly: Encapsulation Efficiency and Thermally Triggered Release

    PubMed Central

    2015-01-01

    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

  8. 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

  9. 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

  10. High Sensitive and Selective Sensing of Hydrogen Peroxide Released from Pheochromocytoma Cells Based on Pt-Au Bimetallic Nanoparticles Electrodeposited on Reduced Graphene Sheets

    PubMed Central

    Yu, Guangxia; Wu, Weixiang; Pan, Xiaoqi; Zhao, Qiang; Wei, Xiaoyun; Lu, Qing

    2015-01-01

    In this study, a high sensitive and selective hydrogen peroxide (H2O2) sensor was successfully constructed with Pt-Au bimetallic nanoparticles (Pt-Au NPs)/reduced graphene sheets (rGSs) hybrid films. Various molar ratios of Au to Pt and different electrodeposition conditions were evaluated to control the morphology and electrocatalytic activity of the Pt-Au bimetallic nanoparticles. Upon optimal conditions, wide linear ranges from 1 µM to 1.78 mM and 1.78 mM to 16.8 mM were obtained, with a detection limit as low as 0.31 µM. Besides, due to the synergetic effects of the bimetallic NPs and rGSs, the amperometric H2O2 sensor could operate at a low potential of 0 V. Under this potential, not only common anodic interferences induced from ascorbic acid, uric acid and dopamine, but also the cathodic interference induced from endogenous O2 could be effectively avoided. Furthermore, with rat pheochromocytoma cells (PC 12) as model, the proposed sensor had been successfully used in the detection of H2O2 released from the cancer cells. This method with wide linear ranges and excellent selectivity can provide a promising alternative for H2O2 monitoring in vivo in the fields of physiology, pathology and diagnosis. PMID:25629706

  11. pH-Responsive Poly(D,L-lactic-co-glycolic acid) Nanoparticles with Rapid Antigen Release Behavior Promote Immune Response.

    PubMed

    Liu, Qi; Chen, Xiaoming; Jia, Jilei; Zhang, Weifeng; Yang, Tingyuan; Wang, Lianyan; Ma, Guanghui

    2015-05-26

    In the quest to treat intracellular infectious diseases and virus infection, nanoparticles (NPs) have been considered to be efficient tools for inducing potent immune responses, specifically cellular immunity. Antigen processing and presenting by antigen presenting cells (APCs) could influence immune response, especially the priming of T-cell-mediated cellular immunity. Here, we fabricated pH-responsive poly(D,L-lactic-co-glycolic acid) (PLGA) NPs with rapid antigen intracellular release behavior in APCs. The NPs, which had thin shells and large inner space, contain ammonium bicarbonate (NH4HCO3), which could regulate release in endosomes and lysosomes, acting as an antigen release promoter in dendritic cells (DCs), and were coencapsulated with antigen (ovalbumin, OVA). Hydrogen ions (H(+)) in DC endosomes and lysosomes (pH ∼5.0 and 6.5) could react with NH4HCO3 to generate NH3 and CO2, which broke NPs and released antigens. After uptake by DCs, antigens encapsulated in pH-responsive PLGA NPs could escape from lysosomes into the cytoplasm and be cross-presented. Moreover, the NPs induced up-regulation of co-stimulatory molecules and stimulated cytokine production. Mouse immunization with pH-responsive PLGA NPs induced greater lymphocyte activation, more antigen-specific CD8(+) T cells, stronger cytotoxic capacity (IFN-γ and granzyme B), enhanced antigen-specific IgG antibodies, and higher serum IgG2a/IgG1, indicating cellular immunity. The NPs also improved generation of memory T cells to protect against reinfection. Thus, pH-responsive PLGA NPs, which induced strong cellular immune responses and offered antibody protection, could be potentially useful as effective vaccine delivery and adjuvant systems for the therapy of intracellular infectious diseases and virus infection. PMID:25898266

  12. A macromolecular delivery vehicle for protein-based vaccines: Acid-degradable protein-loaded microgels

    PubMed Central

    Murthy, Niren; Xu, Mingcheng; Schuck, Stephany; Kunisawa, Jun; Shastri, Nilabh; Fréchet, Jean M. J.

    2003-01-01

    The development of protein-based vaccines remains a major challenge in the fields of immunology and drug delivery. Although numerous protein antigens have been identified that can generate immunity to infectious pathogens, the development of vaccines based on protein antigens has had limited success because of delivery issues. In this article, an acid-sensitive microgel material is synthesized for the development of protein-based vaccines. The chemical design of these microgels is such that they degrade under the mildly acidic conditions found in the phagosomes of antigen-presenting cells (APCs). The rapid cleavage of the microgels leads to phagosomal disruption through a colloid osmotic mechanism, releasing protein antigens into the APC cytoplasm for class I antigen presentation. Ovalbumin was encapsulated in microgel particles, 200–500 nm in diameter, prepared by inverse emulsion polymerization with a synthesized acid-degradable crosslinker. Ovalbumin is released from the acid-degradable microgels in a pH-dependent manner; for example, microgels containing ovalbumin release 80% of their encapsulated proteins after 5 h at pH 5.0, but release only 10% at pH 7.4. APCs that phagocytosed the acid-degradable microgels containing ovalbumin were capable of activating ovalbumin-specific cytoxic T lymphocytes. The acid-degradable microgels developed in this article should therefore find applications as delivery vehicles for vaccines targeted against viruses and tumors, where the activation of cytoxic T lymphocytes is required for the development of immunity. PMID:12704236

  13. 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

  14. 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

  15. 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 40nm 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 1cm×3cm 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 12days of operation. Further analysis indicated that silver ion release can be sustained for approximately 25days. 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. PMID:26952479

  16. 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

  17. The properties of mesoporous silica nanoparticles functionalized with different PEG-chain length via the disulfide bond linker and drug release in glutathione medium.

    PubMed

    Xie, Zhifei; Gong, Huameng; Liu, Mingxing; Zhu, Hongda; Sun, Honghao

    2016-01-01

    In this paper, a novel drug-loaded material (MSNs-SS-PEG) was obtained by grafting the thiol-linked methoxy polyethylene glycol (MeOPEG-SH) onto the thiol-functionalized mesoporous silica nanoparticles (MSNs-SH) via the disulfide bond linker. In our designed experiment, three different chain lengths of PEG (PEG(1000), PEG(5000), and PEG(1000)-PEG(5000)) were used. The silica materials were characterized by Fourier transform infrared spectroscopy (FT-IR), dynamic light scattering, field emission scanning electron microscopy, transmission electron microscopy, nitrogen adsorption-desorption measurements, and X-ray diffraction. The morphology of the MSNs-SS-PEG was spherical with an average diameter of about 150 nm. Due to the covalent modification of hydrophilic MeOPEG, the MSNs-SS-PEG was coated by a thin polymer shell, showing stable and inerratic MCM-41 type mesoporous structure as well as high specific surface areas and large pore volumes. Moreover, the releases of doxorubicin hydrochloride (DOX) from these materials at 10 mM of glutathione were investigated. The PEG functionalization could effectively cap drugs in the mesoporous channels. The release of DOX from the MSNs-SS-PEG(n) revealed redox-responsive characteristic. The obtained results showed that the MSNs-SS-PEG might be promising drug delivery carrier materials, which could play an important role in the development of drug delivery. PMID:26540096

  18. Metal ion-assisted drug-loading model for novel delivery system of cisplatin solid lipid nanoparticles with improving loading efficiency and sustained release.

    PubMed

    Yang, Caiqin; Lv, Jie; Lv, Tao; Pan, Yahui; Han, Yazhu; Zhao, Sha; Wang, Jing

    2016-05-01

    Metal ion-assisted drug loading model, in which metal ion was used to modify the microstructure of lipid layer, has been developed to improve drug loading efficiency of solid lipid nanoparticles (SLNs). The microstructure and properties of metal ion-assisted cisplatin-loading SLNs were investigated by infra-red spectroscopy, fluorescence spectroscopy and zetasizer. The reactions of hydrogenated soybean lecithin with Zn(2+), Cu(2+), Mn(2+ )and Mg(2+ )have been detected; the mechanism for higher drug encapsulation efficiency (EE) has been investigated. In metal ion introduction SLNs, the compact degree of the lipid molecules was increased due to the electrostatic interaction between metal ions and phospholipid acyl and choline polarity groups, which result in increasing of drug EE. Meanwhile, these electrostatic interactions slowed the releasing rate of encapsulated drug. The study of cytotoxic activity in vitro indicated that the cell cytotoxicity of metal ions introduction SLNs depended on both cell uptake of SLNs and drug releasing from SLNs. PMID:27113257

  19. Nanoparticles activate the NLR pyrin domain containing 3 (Nlrp3) inflammasome and cause pulmonary inflammation through release of IL-1α and IL-1β

    PubMed Central

    Yazdi, Amir S.; Guarda, Greta; Riteau, Nicolas; Drexler, Stefan K.; Tardivel, Aubry; Couillin, Isabelle; Tschopp, Jürg

    2010-01-01

    Nanoparticles are increasingly used in various fields, including biomedicine and electronics. One application utilizes the opacifying effect of nano-TiO2, which is frequently used as pigment in cosmetics. Although TiO2 is believed to be biologically inert, an emerging literature reports increased incidence of respiratory diseases in people exposed to TiO2. Here, we show that nano-TiO2 and nano-SiO2, but not nano-ZnO, activate the NLR pyrin domain containing 3 (Nlrp3) inflammasome, leading to IL-1β release and in addition, induce the regulated release of IL-1α. Unlike other particulate Nlrp3 agonists, nano-TiO2–dependent-Nlrp3 activity does not require cytoskeleton-dependent phagocytosis and induces IL-1α/β secretion in nonphagocytic keratinocytes. Inhalation of nano-TiO2 provokes lung inflammation which is strongly suppressed in IL-1R– and IL-1α–deficient mice. Thus, the inflammation caused by nano-TiO2 in vivo is largely caused by the biological effect of IL-1α. The current use of nano-TiO2 may present a health hazard due to its capacity to induce IL-1R signaling, a situation reminiscent of inflammation provoked by asbestos exposure. PMID:20974980

  20. Development and optimization of oil-filled lipid nanoparticles containing docetaxel conjugates designed to control the drug release rate in vitro and in vivo

    PubMed Central

    Feng, Lan; Wu, Huali; Ma, Ping; Mumper, Russell J; Benhabbour, S Rahima

    2011-01-01

    Three docetaxel (DX) lipid conjugates: 2′-lauroyl-docetaxel (C12-DX), 2′-stearoyl-docetaxel (C18-DX), and 2′-behenoyl-docetaxel (C22-DX) were synthesized to enhance drug loading, entrapment, and retention in liquid oil-filled lipid nanoparticles (NPs). The three conjugates showed ten-fold higher solubility in the liquid oil phase Miglyol 808 than DX. To further increase the drug entrapment efficiency in NPs, orthogonal design was performed. The optimized formulation was composed of Miglyol 808, Brij 78, and Vitamin E tocopheryl polyethylene glycol succinate (TPGS). The conjugates were successfully entrapped in the reduced-surfactant NPs with entrapment efficiencies of about 50%–60% as measured by gel permeation chromatography (GPC) at a final concentration of 0.5 mg/mL. All three conjugates showed 45% initial burst release in 100% mouse plasma. Whereas C12-DX showed another 40% release over the next 8 hours, C18-DX and C22-DX in NPs showed no additional release after the initial burst of drug. All conjugates showed significantly lower cytotoxicity than DX in human DU-145 prostate cancer cells. The half maximal inhibitory concentration values (IC50) of free conjugates and conjugate NPs were comparable except for C22-DX, which was nontoxic in the tested concentration range and showed only vehicle toxicity when entrapped in NPs. In vivo, the total area under the curve (AUC0–∞) values of all DX conjugate NPs were significantly greater than that of Taxotere, demonstrating prolonged retention of drug in the blood. The AUC0–∞ value of DX in Taxotere was 8.3-fold, 358.0-fold, and 454.5-fold lower than that of NP-formulated C12-DX, C18-DX, and C22-DX, respectively. The results of these studies strongly support the idea that the physical/chemical properties of DX conjugates may be fine-tuned to influence the affinity and retention of DX in oil-filled lipid NPs, which leads to very different pharmacokinetic profiles and blood exposure of an otherwise potent

  1. Bactericidal activity and silver release of porous ceramic candle filter prepared by sintering silica with silver nanoparticles/zeolite for water disinfection

    NASA Astrophysics Data System (ADS)

    Trinh Nguyen, Thuy Ai; Phu Dang, Van; Duy Nguyen, Ngoc; Le, Anh Quoc; Thanh Nguyen, Duc; Hien Nguyen, Quoc

    2014-09-01

    Porous ceramic candle filters (PCCF) were prepared by sintering silica from rice husk with silver nanoparticles (AgNPs)/zeolite A at about 1050 °C to create bactericidal PCCF/AgNPs for water disinfection. The silver content in PCCF/AgNPs was of 300-350 mg kg-1 determined by inductively coupled plasma-atomic emission spectroscopy (ICP-AES) and the average pore size of PCCF/AgNPs was of 50-70 Å measured by Brunauer-Emmett-Teller (BET) method. The bactericidal activity and silver release of PCCF/AgNPs have been investigated by flow test with water flow rate of 5 L h-1 and initial inoculation of E. coli in inlet water of 106 CFU/100 mL. The volume of filtrated water was collected up to 500 L. Results showed that the contamination of E. coli in filtrated water was <1 CFU/100 mL and the content of silver released from PCCF/AgNPs into filtrated water was <1 μg L-1, it is low, far under the WHO guideline of 100 μg L-1 at maximum for drinking water. Based on the content of silver in PCCF/AgNPs and in filtrated water, it was estimated that one PCCF/AgNPs could be used to filtrate of ˜100 m3 water. Thus, as-prepared PCCF/AgNPs releases low content of silver into water and shows effectively bactericidal activity that is promising to apply as point-of-use water treatment technology for drinking water disinfection.

  2. 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

  3. 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

  4. 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

  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. Optimization of controlled release nanoparticle formulation of verapamil hydrochloride using artificial neural networks with genetic algorithm and response surface methodology.

    PubMed

    Li, Yongqiang; Abbaspour, Mohammadreza R; Grootendorst, Paul V; Rauth, Andrew M; Wu, Xiao Yu

    2015-08-01

    This study was performed to optimize the formulation of polymer-lipid hybrid nanoparticles (PLN) for the delivery of an ionic water-soluble drug, verapamil hydrochloride (VRP) and to investigate the roles of formulation factors. Modeling and optimization were conducted based on a spherical central composite design. Three formulation factors, i.e., weight ratio of drug to lipid (X1), and concentrations of Tween 80 (X2) and Pluronic F68 (X3), were chosen as independent variables. Drug loading efficiency (Y1) and mean particle size (Y2) of PLN were selected as dependent variables. The predictive performance of artificial neural networks (ANN) and the response surface methodology (RSM) were compared. As ANN was found to exhibit better recognition and generalization capability over RSM, multi-objective optimization of PLN was then conducted based upon the validated ANN models and continuous genetic algorithms (GA). The optimal PLN possess a high drug loading efficiency (92.4%, w/w) and a small mean particle size (∼100nm). The predicted response variables matched well with the observed results. The three formulation factors exhibited different effects on the properties of PLN. ANN in coordination with continuous GA represent an effective and efficient approach to optimize the PLN formulation of VRP with desired properties. PMID:25986587

  7. Inclusion of the poorly water-soluble drug simvastatin in mesocellular foam nanoparticles: drug loading and release properties.

    PubMed

    Zhang, Yanzhuo; Zhang, Jinghai; Jiang, Tongying; Wang, Siling

    2011-05-30

    The purpose of this study was to develop spherical mesocellular foam (MCF) loaded with a poorly water-soluble drug, intended to be orally administered, able to improve the dissolution rate and enhance the drug loading capacity. Spherical MCF with a continuous 3-D pore system was synthesized using Pluronic 123 triblock polymer (P123) as a surfactant coupled with cetyltrimethyl ammonium bromide (CTAB) as a co-surfactant. A model drug, simvastatin (SV), was loaded onto spherical MCF via a procedure involving a combination of adsorption equilibrium and solvent evaporation. The drug release rate and the drug loading efficiency of spherical MCF were compared with those of fibrous SBA-15. Investigations using nitrogen adsorption, scanning electron microscopy (SEM), transmission electron microscopy (TEM), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and HPLC demonstrated the successful incorporation of SV into the MCF host. It was found that spherical MCF has a high drug loading efficiency up to 37.5%, and higher than that of fibrous SBA-15 with a pore diameter of 6.5 nm. It is worth noting that fast release rate of SV was obtained from spherical MCF compared with SBA-15 and pure crystalline SV using enzyme-free simulated intestinal fluid (SIF, pH 6.8). PMID:20674729

  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. New formulation of an old drug in hypertension treatment: the sustained release of captopril from cyclodextrin nanoparticles

    PubMed Central

    de Azevedo, Mariangela de Burgos M; Tasic, Ljubica; Fattori, Juliana; Rodrigues, Fábio HS; Cantos, Fabiana C; Ribeiro, Leandro P; de Paula, Vanice; Ianzer, Danielle; Santos, Robson AS

    2011-01-01

    Captopril (CAP) was the first angiotensin I-converting enzyme (ACE) inhibitor to be developed and is widely used in hypertension treatment. On the other hand, cyclodextrins (CDs) are cyclic oligosaccharides whose cone-shaped cavity allows formation of noncovalent inclusion complexes with appropriately sized guest molecules, thus modifying guest physical, chemical, and biological properties. Herein, the physicochemical characterization and in vivo ACE inhibition evaluation of seven CAP/CD complexes are reported. The inclusion complexes were prepared by spray-drying, freeze-drying, kneading, or lyophilization methods and characterized by nuclear magnetic resonance, Fourier-transformed infrared spectroscopy, X-ray diffraction, differential scanning calorimetry, and scanning electron microscopy techniques. In vivo assays compared CAP and CAP/CD complex administration (0.5 mg kg−1 or 0.09 mg kg−1, n = 4–7) to evaluate the ACE inhibition by continuous infusion of angiotensin I (30 ng 50 μL−1 min−1) in conscious Wistar rats. The physicochemical analysis demonstrated complete amorphization and complexation between CAP and CDs, indicating the substitution of water molecules inside the CD cavity with CAP. During the infusion of angiotensin I, the administration of all CAP/CD complexes induced a reduction in mean arterial pressure similar to that observed upon CAP administration. The nanoparticles obtained by the kneading method (CAP/α-CD:KM) showed a potent and long-lasting inhibitory activity (∼22 hours) on the angiotensin I pressor effect. The results suggest that the inclusion complex of CAP and α-CD can function as a novel antihypertensive formulation that may improve therapeutic use of CAP by reducing its oral dose administration to once per day, thus providing better quality of life for almost 25% of the world’s population who suffer from hypertension. PMID:21720512

  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. PMID:21864595

  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. 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.

  14. pH-triggered sustained release of arsenic trioxide by polyacrylic acid capped mesoporous silica nanoparticles for solid tumor treatment in vitro and in vivo.

    PubMed

    Xiao, Xuecheng; Liu, Yangyang; Guo, Manman; Fei, Weidong; Zheng, Hongyue; Zhang, Rongrong; Zhang, Yan; Wei, Yinghui; Zheng, Guohua; Li, Fanzhu

    2016-07-01

    Arsenic trioxide (As2O3, ATO), a FDA approved drug for hematologic malignancies, was proved of efficient growth inhibition of cancer cell in vitro or solid tumor in vivo. However, its effect on solid tumor in vivo was hampered by its poor pharmacokinetics and dose-limited toxicity. In this study, a polyacrylic acid capped pH-triggered mesoporous silica nanoparticles was conducted to improve the pharmacokinetics and enhance the antitumor effect of arsenic trioxide. The mesoporous silica nanoparticles loaded with arsenic trioxide was grafted with polyacrylic acid (PAA-ATO-MSN) as a pH-responsive biomaterial on the surface to achieve the release of drug in acidic microenvironment of tumor, instead of burst release action in circulation. The nanoparticles were characterized with uniform grain size (particle sizes of 158.6 ± 1.3 nm and pore sizes of 3.71 nm, respectively), historically comparable drug loading efficiency (11.42 ± 1.75%), pH-responsive and strengthened sustained release features. The cell toxicity of amino groups modified mesoporous silica nanoparticles (NH2-MSN) was significantly reduced by capping of polyacrylic acid. In pharmacokinetic studies, the half time (t1/2β) was prolonged by 1.3 times, and the area under curve) was increased by 2.6 times in PAA-ATO-MSN group compared with free arsenic trioxide group. Subsequently, the antitumor efficacy in vitro (SMMC-7721 cell line) and in vivo (H22 xenografts) was remarkably enhanced indicated that PAA-ATO-MSN improved the antitumor effect of the drug. These results suggest that the polyacrylic acid capped mesoporous silica nanoparticles (PAA-MSN) will be a promising nanocarrier for improving pharmacokinetic features and enhancing the anti-tumor efficacy of arsenic trioxide. PMID:27059495

  15. 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. PMID:26409200

  16. 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.

  17. 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.

  18. Thermally controlled release of anticancer drug from self-assembled γ-substituted amphiphilic poly(ε-caprolactone) micellar nanoparticles.

    PubMed

    Cheng, Yixing; Hao, Jing; Lee, L Andrew; Biewer, Michael C; Wang, Qian; Stefan, Mihaela C

    2012-07-01

    A thermo-responsive poly{γ-2-[2-(2-methoxyethoxy)ethoxy]ethoxy-ε-caprolactone}-b-poly(γ-octyloxy-ε-caprolactone) (PMEEECL-b-POCTCL) diblock copolymer was synthesized by ring-opening polymerization using tin octanoate (Sn(Oct)(2)) catalyst and a fluorescent dansyl initiator. The PMEEECL-b-POCTCL had a lower critical solution temperature (LCST) of 38 °C, and it was employed to prepare thermally responsive micelles. Nile Red and Doxorubicin (DOX) were loaded into the micelles, and the micellar stability and drug carrying ability were investigated. The size and the morphology of the cargo-loaded micelles were determined by DLS, AFM, and TEM. The Nile-Red-loaded polymeric micelles were found to be stable in the presence of both fetal bovine serum and bovine serum albumin over a 72 h period and displayed thermo-responsive in vitro drug release. The blank micelles showed a low cytotoxicity. As comparison, the micelles loaded with DOX showed a much higher in vitro cytotoxicity against MCF-7 human breast cancer cell line when the incubation temperature was elevated above the LCST. Confocal laser scanning microscopy was used to study the cellular uptake and showed that the DOX-loaded micelles were internalized into the cells via an endocytosis pathway. PMID:22681332

  19. 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. PMID:26740466

  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. Topically applied NO-releasing nanoparticles can increase intracorporal pressure and elicit spontaneous erections in a rat model of radical prostatectomy

    PubMed Central

    Tar, Moses; Cabrales, Pedro; Mahantesh, Navarti; Adler, Brandon; Nacharaju, Parimala; Friedman, Adam; Friedman, Joel; Davies, Kelvin P.

    2014-01-01

    Introduction Patients undergoing radical prostatectomy (RP) suffer from erectile dysfunction (ED) refractory to PDE5 inhibitors, which act downstream of CN-mediated release of nitric oxide (NO). Direct delivery of NO to the penis could potentially circumvent this limitation. Aim To determine if topically applied NO-releasing nanoparticles (NO-np) can elicit erections in a rat model of RP and demonstrate that the mechanism is through increased blood flow. Methods 26 Sprague–Dawley rats underwent bilateral transection of the CN. One week later NO-np were applied topically to the penile shaft in DMSO-gel (10 animals) or coconut oil (6 animals). Control animals were treated with empty-np. Erectile function was determined through the intracorporal pressure/blood pressure ratio (ICP/BP). The effect of the NO-np on blood flow was determined using a hamster dorsal window chamber. Main Outcome Measures Animals were investigated for spontaneous erections, onset and duration of erectile response and basal ICP/BP ratio. Microcirculatory blood-flow was determined through arteriolar and venular diameter and blood flow. Results Eight of ten animals treated with NO-np suspended in DMSO-gel had significant increases in basal ICP/BP, and six out of these ten animals demonstrated spontaneous erections of approximately one minute duration. Onset of spontaneous erections ranged from 5–37 minutes and occurred for at least 45 minutes. Similar results were observed with NO-np applied in coconut oil. No erectile response was observed in control animal models treated with empty-np. The hamster dorsal window chamber demonstrated NO-np applied as a suspension in coconut oil caused a significant increase in the microcirculatory blood flow, sustained over 90 minutes. Conclusions Topically applied NO-np induced spontaneous erections and increased basal ICP in an animal model of RP. These effects are most likely due to increased microcirculatory blood flow. These characteristics suggest that

  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. PMID:27281168

  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. PMID:26478017

  5. 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

  6. Traceable Nanoparticle Delivery of Small Interfering RNA and Retinoic Acid with Temporally Release Ability to Control Neural Stem Cell Differentiation for Alzheimer's Disease Therapy.

    PubMed

    Zhang, Ran; Li, Yan; Hu, Bingbing; Lu, Zhiguo; Zhang, Jinchao; Zhang, Xin

    2016-08-01

    Nanoparticles that can efficiently control the differentiation of neural stem cells (NSCs) into neurons are developed for Alzheimer's disease (AD) therapy. The treatment with these nanoparticles results in an attenuation of neuronal loss and rescues memory deficiencies in mice. The system can also be used to monitor the transplantation site, as well as the migration of NSCs in real time. Therefore, the system is proposed to open up new avenues for AD treatment. PMID:27168033

  7. 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

  8. 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...

  9. 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...

  10. Encapsulation of indole-3-carbinol and 3'3'-diindolylmethane in zein/carboxymethyl chitosan nanoparticles with controlled release property and improved stability

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Indole-3-carbinol (I3C) and diindolylmethane (DIM) are two bioactive compounds from Cruciferous vegetables. Their stabilities are the major challenges for their pharmaceutical applications. In this study, zein and zein/carboxymethyl chitosan (zein/CMCS) nanoparticles have been prepared to encapsulat...

  11. Chemical Aspects of Nanoparticle Ecotoxicology.

    PubMed

    Sigg, Laura; Behra, Renata; Groh, Ksenia; Isaacson, Carl; Odzak, Niksa; Piccapietra, Flavio; Röhder, Lena; Schug, Hannah; Yue, Yang; Schirmer, Kristin

    2014-11-01

    Nanoecotoxicology strives to understand the processes and mechanisms by which engineered nanoparticles (ENP) may exert toxic effects on aquatic organisms. Detailed knowledge of the chemical reactions of nanoparticles in the media and of their interactions with organisms is required to understand these effects. The processes of agglomeration of nanoparticles, of dissolution and release of toxic metal ions, and of production of reactive oxygen species (ROS) are considered in this article. Important questions concern the role of uptake of nanoparticles in various organisms, in contrast to uptake of ions released from nanoparticles and to nanoparticle attachment to organism surfaces. These interactions are illustrated for effects of silver nanoparticles (AgNP), cerium oxide (CeO2 NP) and titanium dioxide (TiO2 NP), on aquatic organisms, including algae, biofilms, fish cells and fish embryos. PMID:26508489

  12. Optimization (Central Composite Design) and Validation of HPLC Method for Investigation of Emtricitabine Loaded Poly(lactic-co-glycolic acid) Nanoparticles: In Vitro Drug Release and In Vivo Pharmacokinetic Studies

    PubMed Central

    Singh, Gurinder; Pai, Roopa S.

    2014-01-01

    The objective of the current study is to develop nanoparticles (NPs) drug delivery system of emtricitabine solely using poly(lactic-co-glycolic acid) (PLGA) and evaluate its in vitro and in vivo release performance by systematically optimized HPLC method using Formulation by Design (FbD). NPs were evaluated for in vitro release and in vivo absorption study. The desired chromatographic separation was achieved on a Phenomenex C18 (250 mm × 4.6 mm I.D., 5 μm) column, under isocratic conditions using UV detection at 280 nm. The optimized mobile phase consisted of a mixture of 40 mM phosphate dihydrogen phosphate buffer (pH 6.8), methanol, and 2% acetonitrile in a ratio of (83 : 15 : 2, v/v/v) at a flow rate of 1 mL/min. The linear regression analysis for the calibration curves showed a good linear correlation over the concentration range 0.040–2.0 μg/mL, with retention time of 4.39 min. An average encapsulation efficiency of 74.34% was obtained for NPs. In vitro studies showed zero-order release and about 95% drug being released within 15 days in PBS (pH 7.4). In conclusion, the proposed optimized method was successfully applied for the determination of in vitro and in vivo release studies of emtricitabine NPs. PMID:24672337

  13. Influence of the primary emulsification procedure on the characteristics of small protein-loaded PLGA microparticles for antigen delivery.

    PubMed

    Wischke, C; Borchert, H-H

    2006-06-01

    Microparticles prepared from poly(lactic-co-glycolic acid) (PLGA) using a W1/O/W2 double emulsion solvent evaporation method are suitable vehicles for the delivery of proteins to antigen presenting cells, e.g. dendritic cells. In this study, the influence of different techniques for the preparation of the primary W1/O emulsion was investigated with respect to the protein localization within the microparticles, morphological characteristics of these particles, protein burst release and the native state of the released protein. Bovine serum albumin bearing fluorescein isothiocyanate (FITC-BSA) was used as model protein. A static micromixer was applied for the preparation of the W1/O/W2 double emulsion. Employing a rotor-stator homogenizer (Ultra-Turrax) for primary emulsification, microcapsules with a high burst release were produced, because nearly all FITC-BSA was attached to the outside of the particle wall. Using a high pressure homogenizer or an ultrasonic procedure resulted in the formation of microspheres with homogeneous protein distribution and a reduced burst release. PMID:16854818

  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. 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

  16. 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

  17. Preparation of andrographolide-loaded solid lipid nanoparticles and their in vitro and in vivo evaluations: characteristics, release, absorption, transports, pharmacokinetics, and antihyperlipidemic activity.

    PubMed

    Yang, Tao; Sheng, Huan-Huan; Feng, Nian-Ping; Wei, Hai; Wang, Zheng-Tao; Wang, Chang-Hong

    2013-12-01

    Andrographolide (AND) is one of diterpenoids separated from Andrographis paniculata with a wide spectrum of biological activities of being anti-inflammatory, anticancer, hepatoprotective, and antihyperlipidemic. But its poor water solubility and instability resulted in lower bioavailability and seriously limited its pharmacological function. In this study, AND-loaded solid lipid nanoparticles (AND-SLNs) were prepared by a high-pressure homogenization method and presented as spherically shaped under transmission electron microscopy with an average diameter of 286.1 nm and zeta potential of -20.8 mV. The average drug-entrapment efficiency and drug loading were 91.00% and 3.49%, respectively. The results indicated that the lower bioavailability of AND is not only because of the poor solubility but also owing to its metabolic instability in intestinal segments. Furthermore, the transport mechanism of AND in Caco-2 cell model is complex in which an active transport carrier (P-glycoprotein) is involved in. The bioavailability and antihyperlipidemic activity of AND were improved by AND-SLNs by increasing the solubility and stability of AND in the intestine and by changing its transport mode in Caco-2 cell. The bioavailability of AND was increased to 241% by AND-SLNs as compared with AND suspension. AND-SLNs would be a promising drug-delivery system to enhance the oral absorption and bioavailability of AND. PMID:24166599

  18. 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.

  19. Zonal release of proteins within tissue engineering scaffolds.

    PubMed

    Suciati, Tri; Howard, Daniel; Barry, John; Everitt, Nicola M; Shakesheff, Kevin M; Rose, Felicity Raj

    2006-11-01

    The manufacture of a scaffold for tissue engineering applications that can control the location and timing of growth factor release is described. The scaffold is formed by the sintering of poly(DL-lactic acid) (P(DL)LA) microparticles, plasticized with poly(ethylene glycol) (PEG), although the method can be used for many other polymer types. The microparticles were loaded with model proteins, trypsin and horseradish peroxidase (HRP), or recombinant human bone morphogenetic protein-2 (rhBMP-2). Entrapment efficiencies above 75% were achieved using a solid-in-oil-in-water system. Controlled release of active protein was achieved for at least 30 days. Microparticles were built into protein-loaded or protein-free layers and release of the protein was restricted to zones within the scaffold. Cell response to rhBMP-2 was tuneable by changing the dose of the rhBMP-2 released by varying the ratio of protein-loaded and protein-free microparticles within scaffolds. Zonal activity of rhBMP-2 on C2C12 cells was demonstrated. The scaffolds may find utility in applications where gradients of growth factors within 3D templates are required or where zonation of tissue growth is required. PMID:17122918

  20. 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

  1. Controlled uptake and release of imatinib from ultrasound nanoparticles Cu3(BTC)2 metal-organic framework in comparison with bulk structure.

    PubMed

    Abbasi, Amir Reza; Rizvandi, Maryam; Azadbakht, Azadeh; Rostamnia, Sadegh

    2016-06-01

    The porosity of metal-organic frameworks (MOFs) is an important point concerning the possible use of such functional materials for different purposes. In this work, we study uptake and release properties of imatinib (IM) from nano Cu(II)-MOF in comparison with bulk Cu(II)-MOF. To explore the absorption ability of the Cu(II)-MOF to IM, fresh sample of Cu3(BTC)2 was immersed in an aqueous solution of IM and were monitored in real time with UV/vis spectroscopy. Results show that the adsorbed quantity of IM over nano Cu3(BTC)2 (I) is much higher than those over a bulk Cu3(BTC)2 (II). PMID:26994351

  2. Dual-Shell Fluorescent Nanoparticles for Self-Monitoring of pH-Responsive Molecule-Releasing in a Visualized Way.

    PubMed

    Yang, Lingang; Cui, Chuanfeng; Wang, Lingzhi; Lei, Juying; Zhang, Jinlong

    2016-07-27

    The rational design and controlled synthesis of a smart device with flexibly tailored response ability is all along desirable for bioapplication but long remains a considerable challenge. Here, a pH-stimulated valve system with a visualized "on-off" mode is constructed through a dual-shell fluorescence resonance energy transfer (FRET) strategy. The dual shells refer to carbon dots and fluorescent molecules embedded polymethacrylic acid (F-PMAA) layers successively coating around a SiO2 core (ca. 120 nm), which play the roles as energy donor and acceptor, respectively. The total thickness of the dual-shell in the solid composite is ca. 10 nm. The priorities of this dual-shell FRET nanovalve stem from three facts: (1) the thin shell allows the formation of efficient FRET system without chemical bonding between energy donor and acceptor; (2) the maximum emission wavelength of CD layer is tunable in the range of 400-600 nm, thus providing a flexible energy donor for a wide variety of energy acceptors; (3) the outer F-PMAA shell with a pH-sensitive swelling-shrinking (on-off) behavior functions as a valve for regulating the FRET process. As such, a sensitive and stable pH ratiometric sensor with a working pH range of 3-6 has been built by simply encapsulating pH-responsive fluorescein isothiocyanate (FITC) into PMAA; a pH-dependent swelling-shrinking shuttle carrier with a finely controllable molecule-release behavior has been further fabricated using rhodamine B isothiocyanate (RBITC) as the energy donor and model guest molecule. Significantly, the controlled releasing process is visually self-monitorable. PMID:27377369

  3. SPIO nanoparticle-stabilized PAA-F127 thermosensitive nanobubbles with MR/US dual-modality imaging and HIFU-triggered drug release for magnetically guided in vivo tumor therapy.

    PubMed

    Huang, Hsin-Yang; Hu, Shang-Hsiu; Hung, Shih-Ya; Chiang, Chih-Sheng; Liu, Hao-Li; Chiu, Tsung-Lang; Lai, Hsin-Yi; Chen, You-Yin; Chen, San-Yuan

    2013-11-28

    Nanobubbles can serve as promising, next-generation theranostic platforms for ultrasound (US) and magnetic resonance (MR) imaging, and combined magnetic targeting (MT) and high-intensity focused ultrasound (HIFU)-triggered drug release for tumor therapy. Nanobubble-based dual contrast enhancement agents encapsulated with perfluoropentane and stabilized with superparamagnetic iron oxide (SPIO) nanoparticles have been synthesized through a single-step emulsion process from thermosensitive F127 and polyacrylic acid (PAA). Both US and MR imaging contrast can be optimized by varying the shell thickness and SPIO-embedded concentration. The US contrast can be enhanced from a mean gray value of 62 to 115, and the MR r2 value can be enhanced from 164 to 208 (s(-1)mM (-1)Fe) by increasing the SPIO concentration from 14.1 to 28.2mg/mL, respectively. In vivo investigations of SPIO-embedded nanobubbles in excised tumors under external MT revealed that the US and MR signals change quantitatively compared to the same site without MT. This combined strategy enables the nanobubbles to enhance both passive targeting (increasing the permeability by HIFU) and physical MT of chemotherapeutic drugs to tumors. The integration of functionalities makes this nanobubble system a powerful and viable new tool to achieve simultaneous in vivo tumor imaging and efficacious cancer therapy. PMID:23933522

  4. Nanotechnologies for Noninvasive Measurement of Drug Release

    PubMed Central

    Moore, Thomas; Chen, Hongyu; Morrison, Rachel; Wang, Fenglin; Anker, Jeffrey N.; Alexis, Frank

    2014-01-01

    A wide variety of chemotherapy and radiotherapy agents are available for treating cancer, but a critical challenge is to deliver these agents locally to cancer cells and tumors while minimizing side effects from systemic delivery. Nanomedicine uses nanoparticles with diameters in the range of ~1–100 nm to encapsulate drugs and target them to tumors. The nanoparticle enhances local drug delivery effciency to the tumors via entrapment in leaky tumor vasculature, molecular targeting to cells expressing cancer biomarkers, and/or magnetic targeting. In addition, the localization can be enhanced using triggered release in tumors via chemical, thermal, or optical signals. In order to optimize these nanoparticle drug delivery strategies, it is important to be able to image where the nanoparticles distribute and how rapidly they release their drug payloads. This Review aims to evaluate the current state of nanotechnology platforms for cancer theranostics (therapeutic and diagnostic particles) that are capable of noninvasive measurement of release kinetics. PMID:24215280

  5. Local Affinity Release.

    PubMed

    Delplace, Vianney; Obermeyer, Jaclyn; Shoichet, Molly S

    2016-07-26

    The use of hydrogels for therapeutic delivery is a burgeoning area of investigation. These water-swollen polymer matrices are ideal platforms for localized drug delivery that can be further combined with specific ligands or nanotechnologies to advance the controlled release of small-molecule drugs and proteins. Due to the advantage of hydrophobic, electrostatic, or specific extracellular matrix interactions, affinity-based strategies can overcome burst release and challenges associated with encapsulation. Future studies will provide innovative binding tools, truly stimuli-responsive systems, and original combinations of emerging technologies to control the release of therapeutics spatially and temporally. Local drug delivery can be achieved by directly injecting a therapeutic to its site of action and is advantageous because off-target effects associated with systemic delivery can be minimized. For prolonged benefit, a vehicle that provides sustained drug release is required. Hydrogels are versatile platforms for localized drug release, owing to the large library of biocompatible building blocks from which they can be formed. Injectable hydrogel formulations that gel quickly in situ and provide sustained release of therapeutics are particularly advantageous to minimize invasiveness. The incorporation of polymers, ligands or nanoparticles that have an affinity for the therapeutic of interest improve control over the release of small-molecule drugs and proteins from hydrogels, enabling spatial and temporal control over the delivery. Such affinity-based strategies can overcome drug burst release and challenges associated with protein instability, allowing more effective therapeutic molecule delivery for a range of applications from therapeutic contact lenses to ischemic tissue regeneration. PMID:27403513

  6. Nitric Oxide-Releasing Nanoparticles Prevent Propionibacterium acnes-Induced Inflammation by Both Clearing the Organism and Inhibiting Microbial Stimulation of the Innate Immune Response.

    PubMed

    Qin, Min; Landriscina, Angelo; Rosen, Jamie M; Wei, Gabrielle; Kao, Stephanie; Olcott, William; Agak, George W; Paz, Karin B; Bonventre, Josephine; Clendaniel, Alicea; Harper, Stacey; Adler, Brandon L; Krausz, Aimee E; Friedman, Joel M; Nosanchuk, Joshua D; Kim, Jenny; Friedman, Adam J

    2015-11-01

    Propionibacterium acnes induction of IL-1 cytokines through the NLRP3 (NLR, nucleotide oligomerization domain-like receptor) inflammasome was recently highlighted as a dominant etiological factor for acne vulgaris. Therefore, therapeutics targeting both the stimulus and the cascade would be ideal. Nitric oxide (NO), a potent biological messenger, has documented broad-spectrum antimicrobial and immunomodulatory properties. To harness these characteristics to target acne, we used an established nanotechnology capable of generating/releasing NO over time (NO-np). P. acnes was found to be highly sensitive to all concentrations of NO-np tested, although human keratinocyte, monocyte, and embryonic zebra fish assays revealed no cytotoxicity. NO-np significantly suppressed IL-1β, tumor necrosis factor-α (TNF-α), IL-8, and IL-6 from human monocytes, and IL-8 and IL-6 from human keratinocytes, respectively. Importantly, silencing of NLRP3 expression by small interfering RNA did not limit NO-np inhibition of IL-1 β secretion from monocytes, and neither TNF-α nor IL-6 secretion, nor inhibition by NO-np was found to be dependent on this pathway. The observed mechanism by which NO-np impacts IL-1β secretion was through inhibition of caspase-1 and IL-1β gene expression. Together, these data suggest that NO-np can effectively prevent P. acnes-induced inflammation by both clearing the organism and inhibiting microbial stimulation of the innate immune response. PMID:26172313

  7. Nitric Oxide Releasing Nanoparticles prevent Propionibacterium acnes induced inflammation by both clearing the organism and inhibiting microbial stimulation of the innate immune response

    PubMed Central

    Qin, Min; Landriscina, Angelo; Rosen, Jamie; Wei, Gabrielle; Kao, Stephanie; Olcott, William; Agak, George W.; Paz, Karin Blecher; Bonventre, Josephine; Clendaniel, Alicea; Harper, Stacey; Adler, Brandon; Krausz, Aimee; Friedman, Joel; Nosanchuk, Joshua; Kim, Jenny; Friedman, Adam J

    2015-01-01

    Propionibacterium acnes induction of IL-1 cytokines through the NLRP3 inflammasome was recently highlighted as a dominant etiological factor for acne vulgaris. Therefore, therapeutics targeting both the stimulus and the cascade would be ideal. Nitric oxide (NO), a potent biological messenger, has documented broad-spectrum antimicrobial and immunomodulatory properties. To harness these characteristics to target acne, we utilized an established nanotechnology capable of generating/releasing nitric oxide over time (NO-np). P. acnes was found to be highly sensitive to all concentrations of NO-np tested, though human keratinocyte, monocyte, and embryonic zebra fish assays revealed no cytotoxicity. NO-np significantly suppressed IL-1β, TNF-α, IL-8 and IL-6 from human monocytes and IL-8 and IL-6 from human keratinocytes respectively. Importantly, silencing of NLRP3 expression by small interfering RNA did not limit NO-np inhibition of IL-1 β secretion from monocytes, and neither TNF-α, nor IL-6 secretion nor inhibition by NO-np was found to be dependent on this pathway. The observed mechanism by which NO-np impacts IL-1β secretion was through inhibition of caspase-1 and IL-1β gene expression. Together, these data suggest that NO-np can effectively prevent P. acnes induced inflammation by both clearing the organism and inhibiting microbial stimulation of the innate immune response. PMID:26172313

  8. Effects of intratracheally instilled laser printer-emitted engineered nanoparticles in a mouse model: A case study of toxicological implications from nanomaterials released during consumer use

    PubMed Central

    Pirela, Sandra V.; Lu, Xiaoyan; Miousse, Isabelle; Sisler, Jennifer D.; Qian, Yong; Guo, Nancy; Koturbash, Igor; Castranova, Vincent; Thomas, Treye; Godleski, John; Demokritou, Philip

    2016-01-01

    Incorporation of engineered nanomaterials (ENMs) into toners used in laser printers has led to countless quality and performance improvements. However, the release of ENMs during printing (consumer use) has raised concerns about their potential adverse health effects. The aim of this study was to use “real world” printer-emitted particles (PEPs), rather than raw toner powder, and assess the pulmonary responses following exposure by intratracheal instillation. Nine-week old male Balb/c mice were exposed to various doses of PEPs (0.5, 2.5 and 5 mg/kg body weight) by intratracheal instillation. These exposure doses are comparable to real world human inhalation exposures ran