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Sample records for gelatin-based engineered nanocarriers

  1. Genetically engineered nanocarriers for drug delivery

    PubMed Central

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

    2014-01-01

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

  2. Green synthesis of a new gelatin-based antimicrobial scaffold for tissue engineering.

    PubMed

    Yazdimamaghani, Mostafa; Vashaee, Daryoosh; Assefa, Senait; Shabrangharehdasht, Mitra; Rad, Armin Tahmasbi; Eastman, Margaret A; Walker, Kenneth J; Madihally, Sundar V; Köhler, Gerwald A; Tayebi, Lobat

    2014-06-01

    With the aim of developing appropriate scaffolds for tissue engineering to suppress the formation of biofilms, an effective one-pot process was applied in this study to produce scaffolds with inherent antibacterial activity. A new method to synthesize genipin-crosslinked gelatin/nanosilver scaffolds with "green" in situ formation of silver nanoparticles by heat treatment is presented in this paper. In this procedure, toxic solvents, reducing agents, and stabilizing agents are avoided. UV-visible absorption spectra of the synthesized gelatin/nanosilver solutions were obtained immediately and three months after the synthesis revealing the presence and high stability of the silver nanoparticles. The TEM of gelatin/nanosilver solutions showed silver particles with spherical shapes that were less than 5nm in size. Interestingly, contact angle was found to increase from 80° to 125° with the increase in concentration of nanosilver in gelatin. All gelatin/nanosilver solutions showed antimicrobial activity against Staphylococcus aureus and Escherichia coli. However, only the highest concentration showed antifungal effects against Candida albicans pathogens. Scaffolds were prepared by a lyophilization technique from this solution and their antimicrobial activities were examined. Introducing this facile green one-pot process of synthesizing scaffolds with antimicrobial and anti-biofilm properties may lead to key applications in tissue engineering techniques. PMID:24863221

  3. Fabrication and characterization of conductive chitosan/gelatin-based scaffolds for nerve tissue engineering.

    PubMed

    Baniasadi, Hossein; Ramazani S A, Ahmad; Mashayekhan, Shohreh

    2015-03-01

    This paper reports on the development of conductive porous scaffolds by incorporating conductive polyaniline/graphene (PAG) nanoparticles into a chitosan/gelatin matrix for its potential application in peripheral nerve regeneration. The effect of PAG content on the various properties of the scaffold is investigated and the results showed that the electrical conductivity and mechanical properties increased proportional to the increase in the PAG loading, while the porosity, swelling ratio and in vitro biodegradability decreased. In addition, the biocompatibility was evaluated by assessing the adhesion and proliferation of Schwann cells on the prepared scaffolds using SEM and MTT assay, respectively. In summary, this work supports the use of a porous conductive chitosan/gelatin/PAG scaffold with a low amount of PAG (2.5 wt.%) as a suitable material having proper conductivity, mechanical properties and biocompatibility that may be appropriate for different biomedical applications such as scaffold material in tissue engineering for neural repair or other biomedical devices that require electroactivity. PMID:25553968

  4. Engineered nonviral nanocarriers for intracellular gene delivery applications.

    PubMed

    Ojea-Jiménez, Isaac; Tort, Olivia; Lorenzo, Julia; Puntes, Victor F

    2012-10-01

    The efficient delivery of nucleic acids into mammalian cells is a central aspect of cell biology and of medical applications, including cancer therapy and tissue engineering. Non-viral chemical methods have been received with great interest for transfecting cells. However, further development of nanocarriers that are biocompatible, efficient and suitable for clinical applications is still required. In this paper, the different material platforms for gene delivery are comparatively addressed, and the mechanisms of interaction with biological systems are discussed carefully. PMID:22972254

  5. Preparation of gelatin based porous biocomposite for bone tissue engineering and evaluation of gamma irradiation effect on its properties.

    PubMed

    Islam, Md Minhajul; Khan, Mubarak A; Rahman, Mohammed Mizanur

    2015-04-01

    Biodegradable porous hybrid polymer composites were prepared by using gelatin as base polymer matrix, β-tricalcium phosphate (TCP) and calcium sulfate (CS) as cementing materials, chitosan as an antimicrobial agent, and glutaraldehyde and polyethylene glycol (PEG) as crosslinkers at different mass ratios. Thereafter, the composites were subjected to γ-radiation sterilization. The structure and properties of these composite scaffolds were characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), mechanical properties testing (compressive, bending, tensile and impact), thermogravimetry/differential thermal analysis (TG/DTA), and physical stability test in simulated body fluid (SBF). We found that TCP rich composites showed enhanced mechanical properties among all the crosslinked composites. γ-Radiation sterilization triggered further cross linking in polymer matrix resulting a decrease in pore size of the composites and an increase in pore wall thickness with improved mechanical and thermal properties. The chemically crosslinked composite with 40% TCP followed by γ-radiation sterilization showed the smallest pore size distribution with a mean pore diameter of 159.22μm, which falls in the range of 100-350μm - known to be suitable for osteoconduction. Considering its improved mechanical and thermal properties along with osteoconduction ability without cytotoxicity, we propose this biocomposite as a viable candidate for bone tissue engineering. PMID:25686994

  6. Label-Free Ferrocene-Loaded Nanocarrier Engineering for In Vivo Cochlear Drug Delivery and Imaging.

    PubMed

    Youm, Ibrahima; Musazzi, Umberto M; Gratton, Michael Anne; Murowchick, James B; Youan, Bi-Botti C

    2016-10-01

    It is hypothesized that ferrocene (FC)-loaded nanocarriers (FC-NCs) are safe label-free contrast agents for cochlear biodistribution study by transmission electron microscopy (TEM). To test this hypothesis, after engineering, the poly(epsilon-caprolactone)/polyglycolide NCs are tested for stability with various types and ratios of sugar cryoprotectants during freeze-drying. Their physicochemical properties are characterized by UV-visible spectroscopy, dynamic light scattering, Fourier transform infrared spectroscopy, and scanning electron microscopy coupled with energy dispersive X-ray spectroscopy (SEM/EDS). The biodistribution of the FC-NCs in the cochlear tissue after intratympanic injection in guinea pigs is visualized by TEM. Auditory brainstem responses are measured before and after 4-day treatments. These FC-NCs have 153.4 ± 8.7 nm, 85.5 ± 11.2%, and -22.1 ± 1.1 mV as mean diameters, percent drug association efficiency, and zeta potential, respectively (n = 3). The incorporation of FC into the NCs is confirmed by Fourier transform infrared spectroscopy and SEM/EDS spectra. Lactose (3:1 ratio, v/v) is the most effective stabilizer after a 12-day study. The administered NCs are visible by TEM in the scala media cells of the cochlea. Based on auditory brainstem response data, FC-NCs do not adversely affect hearing. Considering the electrondense, radioactive, and magnetic properties of iron inside FC, FC-NCs are promising nanotemplate for future inner ear theranostics. PMID:27449230

  7. Synthesis and Characterization of Gelatin-Based Magnetic Hydrogels

    PubMed Central

    Helminger, Maria; Wu, Baohu; Kollmann, Tina; Benke, Dominik; Schwahn, Dietmar; Pipich, Vitaliy; Faivre, Damien; Zahn, Dirk; Cölfen, Helmut

    2014-01-01

    A simple preparation of thermoreversible gelatin-based ferrogels in water provides a constant structure defined by the crosslinking degree for gelatin contents between 6 and 18 wt%. The possibility of varying magnetite nanoparticle concentration between 20 and 70 wt% is also reported. Simulation studies hint at the suitability of collagen to bind iron and hydroxide ions, suggesting that collagen acts as a nucleation seed to iron hydroxide aggregation, and thus the intergrowth of collagen and magnetite nanoparticles already at the precursor stage. The detailed structure of the individual ferrogel components is characterized by small-angle neutron scattering (SANS) using contrast matching. The magnetite structure characterization is supplemented by small-angle X-ray scattering and microscopy only visualizing magnetite. SANS shows an unchanged gelatin structure of average mesh size larger than the nanoparticles with respect to gel concentration while the magnetite nanoparticles size of around 10 nm seems to be limited by the gel mesh size. Swelling measurements underline that magnetite acts as additional crosslinker and therefore varying the magnetic and mechanical properties of the ferrogels. Overall, the simple and variable synthesis protocol, the cheap and easy accessibility of the components as well as the biocompatibility of the gelatin-based materials suggest them for a number of applications including actuators. PMID:25844086

  8. MULTIFUNCTIONAL AND STIMULI-SENSITIVE PHARMACEUTICAL NANOCARRIERS

    PubMed Central

    Torchilin, Vladimir

    2011-01-01

    Currently used pharmaceutical nanocarriers, such as liposomes, micelles, and polymeric nanoparticles, demonstrate a broad variety of useful properties, such as longevity in the body; specific targeting to certain disease sites; enhanced intracellular penetration; contrast properties allowing for direct carrier visualization in vivo; stimili-sensitivity, and others. Some of those pharmaceutical carriers have already made their way into clinic, while others are still under preclinical development. In certain cases, the pharmaceutical nanocarriers combine several of the listed properties. Long-circulating immunoliposomes capable of prolonged residence in the blood and specific target recognition represent one of examples of this kind. The engineering of multifunctional pharmaceutical nanocarriers combining several useful properties in one particle can significantly enhance the efficacy of many therapeutic and diagnostic protocols. This paper considers the current status and possible future directions in the emerging area of multifunctional nanocarriers with primary attention on the combination of such properties as longevity, targetability, intracellular penetration, contrast loading, and stimuli sensitivity. PMID:18977297

  9. Zwitterionic drug nanocarriers: a biomimetic strategy for drug delivery.

    PubMed

    Jin, Qiao; Chen, Yangjun; Wang, Yin; Ji, Jian

    2014-12-01

    Nanomaterials self-assembled from amphiphilic functional copolymers have emerged as safe and efficient nanocarriers for delivery of therapeutics. Surface engineering of the nanocarriers is extremely important for the design of drug delivery systems. Bioinspired zwitterions are considered as novel nonfouling materials to construct biocompatible and bioinert nanocarriers. As an alternative to poly(ethylene glycol) (PEG), zwitterions exhibit some unique properties that PEG do not have. In this review, we highlight recent progress of the design of drug nanocarriers using a zwitterionic strategy. The possible mechanism of stealth properties of zwitterions was proposed. The advantages of zwitterionic drug nanocarriers deriving from phosphorylcholine (PC), carboxybetaine (CB), and sulfobetaine (SB) are also discussed. PMID:25092584

  10. Injectable nanocarriers for biodetoxification

    NASA Astrophysics Data System (ADS)

    Leroux, Jean-Christophe

    2007-11-01

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

  11. Advances in the use of nanocarriers for cancer diagnosis and treatment.

    PubMed

    Vieira, Débora Braga; Gamarra, Lionel Fernel

    2016-03-01

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

  12. Advances in the use of nanocarriers for cancer diagnosis and treatment

    PubMed Central

    Vieira, Débora Braga; Gamarra, Lionel Fernel

    2016-01-01

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

  13. Topological Analysis, Modeling, and Imaging of Gelatin-Based Hydrogels

    NASA Astrophysics Data System (ADS)

    Koga, Maho; Marmorat, Clement; Rafailovich, Miriam; Talmon, Yishai; Zussman, Eyal; Arinstein, Arkadii

    Gelatin is a component of natural biocompatible scaffolds used in tissue engineering constructs. However, due its supra-molecular structure, the mesh size is drastically larger compared to synthetic polymers having the same moduli, and therefore the Rubber Elastic Theory cannot be used to describe properties of gelatin. Gelatin forms distinct fibrils, bundles of triple helix chains, which form rigid areas. We experimented with two different gel moduli, made possible by varying the concentration of microbial transglutaminase (mTG). mTG forms permanent cross links and affects the morphology of the gelatin by changing the number of fibrils formed. Thus, the mesh size calculated from the Rubber Elastic Theory was much smaller than the actual size of the mesh, as measured from cryoscanning electron microscopy images and fluorescent bead particle migration. We also observed the en-mass migration behavior of dermal fibroblast cells as a function of the substrate rheological response. Our results will present the ability of the cells to sense the structure of the underlying substrate, as well as the absolute value of the modulus. Furthermore, the data will be interpreted in terms of a modified theoretical model, which takes into account the structure and mesh size of the gel.

  14. In situ-forming click-crosslinked gelatin based hydrogels for 3D culture of thymic epithelial cells.

    PubMed

    Truong, Vinh X; Hun, Michael L; Li, Fanyi; Chidgey, Ann P; Forsythe, John S

    2016-07-21

    Hydrogels prepared from naturally derived gelatin can provide a suitable environment for cell attachment and growth, making them favourable materials in tissue engineering. However, physically crosslinked gelatin hydrogels are not stable under physiological conditions while chemical crosslinking of gelatin by radical polymerization may be harmful to cells. In this study, we attached the norbornene functional group to gelatin, which was subsequently crosslinked with a polyethylene glycol (PEG) linker via the nitrile oxide-norbornene click reaction. The rapid crosslinking process allows the hydrogel to be formed within minutes of mixing the polymer solutions under physiological conditions, allowing the gels to be used as injectable materials. The hydrogels properties including mechanical strength, swelling and degradation, can be tuned by changing either the ratio of the reacting groups or the total concentration of the polymer precursors. Murine embryonic fibroblastic cells cultured in soft gels (2 wt% of gelatin and 1 wt% of PEG linker) demonstrated high cell viability as well as similar phenotypic profiles (PDGFRα and MTS15) to Matrigel cultures over 5 days. Thymic epithelial cell and fibroblast co-cultures produced epithelial colonies in these gels following 7 days incubation. These studies demonstrate that gelatin based hydrogels, prepared using "click" crosslinking, provide a robust cell culture platform with retained benefits of the gelatin material, and are therefore suitable for use in various tissue engineering applications. PMID:27217071

  15. Ascorbyl palmitate/DSPE-PEG nanocarriers for oral iron delivery: preparation, characterisation and in vitro evaluation.

    PubMed

    Zariwala, M Gulrez; Farnaud, Sebastien; Merchant, Zahra; Somavarapu, Satyanarayana; Renshaw, Derek

    2014-03-01

    The objective of this study was to encapsulate iron in nanocarriers formulated with ascorbyl palmitate and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine polyethylene glycol (DSPE-PEG) for oral delivery. Blank and iron (Fe) loaded nanocarriers were prepared by a modified thin film method using ascorbyl palmitate and DSPE-PEG. Surface charge of the nanocarriers was modified by the inclusion of chitosan (CHI) during the formulation process. Blank and iron loaded ascorbyl palmitate/DSPE nanocarriers were visualised by transmission electron microscopy (TEM) and physiochemical characterisations of the nanocarriers carried out to determine the mean particle size and zeta potential. Inclusion of chitosan imparted a net positive charge on the nanocarrier surface and also led to an increase in mean particle size. Iron entrapment in ascorbyl palmitate-Fe and ascorbyl palmitate-CHI-Fe nanocarriers was 67% and 76% respectively, suggesting a beneficial effect of chitosan on nanocarrier Fe entrapment. Iron absorption was estimated by measuring Caco-2 cell ferritin formation using ferrous sulphate as a reference standard. Iron absorption from ascorbyl palmitate-Fe (592.17±21.12 ng/mg cell protein) and ascorbyl palmitate-CHI-Fe (800.12±47.6 ng/mg, cell protein) nanocarriers was 1.35-fold and 1.5-fold higher than that from free ferrous sulphate, respectively (505.74±23.73 ng/mg cell protein) (n=6, p<0.05). This study demonstrates for the first time preparation and characterisation of iron loaded ascorbyl palmitate/DSPE PEG nanocarriers, and that engineering of the nanocarriers with chitosan leads to a significant augmentation of iron absorption. PMID:24333557

  16. Engineering Intracellular Delivery Nanocarriers and Nanoreactors from Oxidation-Responsive Polymersomes via Synchronized Bilayer Cross-Linking and Permeabilizing Inside Live Cells.

    PubMed

    Deng, Zhengyu; Qian, Yinfeng; Yu, Yongqiang; Liu, Guhuan; Hu, Jinming; Zhang, Guoying; Liu, Shiyong

    2016-08-24

    Reactive oxygen species (ROS) and oxidative stress are implicated in various physiological and pathological processes, and this feature provides a vital biochemical basis for designing novel therapeutic and diagnostic nanomedicines. Among them, oxidation-responsive micelles and vesicles (polymersomes) of amphiphilic block copolymers have been extensively explored; however, in previous works, oxidation by ROS including H2O2 exclusively leads to microstructural destruction of polymeric assemblies. For oxidation-responsive polymersomes, fast release of encapsulated hydrophilic drugs and bioactive macromolecules will occur upon microstructural disintegration. Under certain application circumstances, this does not meet design requirements for sustained-release drug nanocarriers and long-acting in vivo nanoreactors. Also note that conventional polymersomes possess thick hydrophobic bilayers and compromised membrane permeability, rendering them as ineffective nanocarriers and nanoreactors. We herein report the fabrication of oxidation-responsive multifunctional polymersomes exhibiting intracellular milieu-triggered vesicle bilayer cross-linking, permeability switching, and enhanced imaging/drug release features. Mitochondria-targeted H2O2 reactive polymersomes were obtained through the self-assembly of amphiphilic block copolymers containing arylboronate ester-capped self-immolative side linkages in the hydrophobic block, followed by surface functionalization with targeting peptides. Upon cellular uptake, intracellular H2O2 triggers cascade decaging reactions and generates primary amine moieties; prominent amidation reaction then occurs within hydrophobic bilayer membranes, resulting in concurrent cross-linking and hydrophobic-to-hydrophilic transition of polymersome bilayers inside live cells. This process was further utilized to achieve integrated functions such as sustained drug release, (combination) chemotherapy monitored by fluorescence and magnetic resonance (MR

  17. Preparation and Characterization of Gelatin-Based Mucoadhesive Nanocomposites as Intravesical Gene Delivery Scaffolds

    PubMed Central

    Liu, Ching-Wen; Chang, Li-Ching; Lin, Kai-Jen; Yu, Tsan-Jung; Tsai, Ching-Chung; Wang, Hao-Kuang; Tsai, Tong-Rong

    2014-01-01

    This study aimed to develop optimal gelatin-based mucoadhesive nanocomposites as scaffolds for intravesical gene delivery to the urothelium. Hydrogels were prepared by chemically crosslinking gelatin A or B with glutaraldehyde. Physicochemical and delivery properties including hydration ratio, viscosity, size, yield, thermosensitivity, and enzymatic degradation were studied, and scanning electron microscopy (SEM) was carried out. The optimal hydrogels (H), composed of 15% gelatin A175, displayed an 81.5% yield rate, 87.1% hydration ratio, 42.9 Pa·s viscosity, and 125.8 nm particle size. The crosslinking density of the hydrogels was determined by performing pronase degradation and ninhydrin assays. In vitro lentivirus (LV) release studies involving p24 capsid protein analysis in 293T cells revealed that hydrogels containing lentivirus (H-LV) had a higher cumulative release than that observed for LV alone (3.7-, 2.3-, and 2.3-fold at days 1, 3, and 5, resp.). Lentivirus from lentivector constructed green fluorescent protein (GFP) was then entrapped in hydrogels (H-LV-GFP). H-LV-GFP showed enhanced gene delivery in AY-27 cells in vitro and to rat urothelium by intravesical instillation in vivo. Cystometrogram showed mucoadhesive H-LV reduced peak micturition and threshold pressure and increased bladder compliance. In this study, we successfully developed first optimal gelatin-based mucoadhesive nanocomposites as intravesical gene delivery scaffolds. PMID:25580433

  18. Smart Polymeric Nanocarriers of Met-enkephalin.

    PubMed

    Szweda, Roza; Trzebicka, Barbara; Dworak, Andrzej; Otulakowski, Lukasz; Kosowski, Dominik; Hertlein, Justyna; Haladjova, Emi; Rangelov, Stanislav; Szweda, Dawid

    2016-08-01

    This study describes a novel approach to polymeric nanocarriers of the therapeutic peptide met-enkephalin based on the aggregation of thermoresponsive polymers. Thermoresponsive bioconjugate poly((di(ethylene glycol) monomethyl ether methacrylate)-ran-(oligo(ethylene glycol) monomethyl ether methacrylate) is synthesized by AGET ATRP using modified met-enkephalin as a macroinitiator. The abrupt heating of bioconjugate water solution leads to the self-assembly of bioconjugate chains and the formation of mesoglobules of controlled sizes. Mesoglobules formed by bioconjugates are stabilized by coating with cross-linked two-layer shell via nucleated radical polymerization of N-isopropylacrylamide using a degradable cross-linker. The targeting peptide RGD, containing the fluorescence marker carboxyfluorescein, is linked to a nanocarrier during the formation of the outer shell layer. In the presence of glutathione, the whole shell is completely degradable and the met-enkephalin conjugate is released. It is anticipated that precisely engineered nanoparticles protecting their cargo will emerge as the next-generation platform for cancer therapy and many other biomedical applications. PMID:27409457

  19. [Hybrid nanocarriers for controlled delivery of antitumour and retroviral drugs delivery].

    PubMed

    Horcajada, Patricia; Serre, Christian; Férey, Gérard; Couvreur, Patrick; Gref, Ruxandra

    2010-01-01

    The efficient delivery of drugs in the body requires the use of non-toxic nanocarriers. Most of the existing materials show poor drug loading and/or rapid release of the proportion of the drug that is simply adsorbed (or anchored) at the external surface of the nanocarrier. The new porous hybrid solids, with the ability to tune their structures and porosities are well suited to serve as nanocarriers for delivery and imaging applications. Here we show that specific non-toxic porous iron(III) - based metal - organic frameworks with engineered cores and surfaces, as well as imaging properties, function as superior nanocarriers for efficient controlled delivery of antitumour and retroviral drugs against cancer and AIDS. They also potentially associate therapeutics and diagnostics, and open the way for theranostics, or -personalized patient treatments. double dagger. PMID:20819715

  20. Dual-Functionalized Theranostic Nanocarriers.

    PubMed

    Mo, Alexander H; Zhang, Chen; Landon, Preston B; Janetanakit, Woraphong; Hwang, Michael T; Santacruz Gomez, Karla; Colburn, David A; Dossou, Samuel M; Lu, Tianyi; Cao, Yue; Sant, Vrinda; Sud, Paul L; Akkiraju, Siddhartha; Shubayev, Veronica I; Glinsky, Gennadi; Lal, Ratnesh

    2016-06-15

    Nanocarriers with the ability to spatially organize chemically distinct multiple bioactive moieties will have wide combinatory therapeutic and diagnostic (theranostic) applications. We have designed dual-functionalized, 100 nm to 1 μm sized scalable nanocarriers comprising a silica golf ball with amine or quaternary ammonium functional groups located in its pits and hydroxyl groups located on its nonpit surface. These functionalized golf balls selectively captured 10-40 nm charged gold nanoparticles (GNPs) into their pits. The selective capture of GNPs in the golf ball pits is visualized by scanning electron microscopy. ζ potential measurements and analytical modeling indicate that the GNP capture involves its proximity to and the electric charge on the surface of the golf balls. Potential applications of these dual-functionalized carriers include distinct attachment of multiple agents for multifunctional theranostic applications, selective scavenging, and clearance of harmful substances. PMID:27144808

  1. Supramolecular nanocarriers with photoresponsive cargo

    NASA Astrophysics Data System (ADS)

    Zhang, Yang; Tang, Sicheng; Thapaliya, Ek Raj; Raymo, FranÒ«isco M.

    2016-03-01

    The covalent integration of fluorescent and photoswitchable components within the same molecular skeleton can be exploited to activate fluorescence under optical control. Specifically, a photoswitchable oxazine heterocycle can be connected to either a coumarin or a borondipyrromethene fluorophore. Illumination of the resulting molecular dyads at an appropriate activation wavelength either opens the heterocycle reversibly or cleaves it irreversibly, depending on the relative positions of its methylene and nitro substituents. These photochemical transformations shift bathochromically the main absorption band of the fluorophore and allow its selective excitation at a given wavelength. These hydrophobic molecular dyads can be entrapped within the hydrophobic interior of self-assembling nanoparticles of amphiphilic polymer. The supramolecular envelope around the switchable compounds enables their transfer into aqueous environments and their operation under these conditions with minimal influence on their photochemical and photophysical properties. The reversible fluorescence activation, possible in one instance, imposes intermittence on the detected emission and offers the opportunity to resolve closely-spaced nanocarriers in time to reconstruct images with subdiffraction resolution. The irreversible fluorescence activation, possible in the other, maintains emission on after the activation event and permits the monitoring of the diffusion of the activated nanocarriers in real time with the sequential acquisition of images. Thus, these operating principles to solubilize and operate photoswitchable fluorophores in aqueous environments with the aid of supramolecular nanocarriers can lead to valuable protocols to image specimens with subdiffraction resolution and to monitor dynamic events noninvasively.

  2. In vivo performance of novel soybean/gelatin-based bioactive and injectable hydroxyapatite foams.

    PubMed

    Kovtun, Anna; Goeckelmann, Melanie J; Niclas, Antje A; Montufar, Edgar B; Ginebra, Maria-Pau; Planell, Josep A; Santin, Matteo; Ignatius, Anita

    2015-01-01

    Major limitations of calcium phosphate cements (CPCs) are their relatively slow degradation rate and the lack of macropores allowing the ingrowth of bone tissue. The development of self-setting cement foams has been proposed as a suitable strategy to overcome these limitations. In previous work we developed a gelatine-based hydroxyapatite foam (G-foam), which exhibited good injectability and cohesion, interconnected porosity and good biocompatibility in vitro. In the present study we evaluated the in vivo performance of the G-foam. Furthermore, we investigated whether enrichment of the foam with soybean extract (SG-foam) increased its bioactivity. G-foam, SG-foam and non-foamed CPC were implanted in a critical-size bone defect in the distal femoral condyle of New Zealand white rabbits. Bone formation and degradation of the materials were investigated after 4, 12 and 20weeks using histological and biomechanical methods. The foams maintained their macroporosity after injection and setting in vivo. Compared to non-foamed CPC, cellular degradation of the foams was considerably increased and accompanied by new bone formation. The additional functionalization with soybean extract in the SG-foam slightly reduced the degradation rate and positively influenced bone formation in the defect. Furthermore, both foams exhibited excellent biocompatibility, implying that these novel materials may be promising for clinical application in non-loaded bone defects. PMID:25448348

  3. In vivo performance of novel soybean/gelatin-based bioactive and injectable hydroxyapatite foams

    PubMed Central

    Kovtun, Anna; Goeckelmann, Melanie J.; Niclas, Antje A.; Montufar, Edgar B.; Ginebra, Maria-Pau; Planell, Josep A.; Santin, Matteo; Ignatius, Anita

    2015-01-01

    Major limitations of calcium phosphate cements (CPCs) are their relatively slow degradation rate and the lack of macropores allowing the ingrowth of bone tissue. The development of self-setting cement foams has been proposed as a suitable strategy to overcome these limitations. In previous work we developed a gelatine-based hydroxyapatite foam (G-foam), which exhibited good injectability and cohesion, interconnected porosity and good biocompatibility in vitro. In the present study we evaluated the in vivo performance of the G-foam. Furthermore, we investigated whether enrichment of the foam with soybean extract (SG-foam) increased its bioactivity. G-foam, SG-foam and non-foamed CPC were implanted in a critical-size bone defect in the distal femoral condyle of New Zealand white rabbits. Bone formation and degradation of the materials were investigated after 4, 12 and 20 weeks using histological and biomechanical methods. The foams maintained their macroporosity after injection and setting in vivo. Compared to non-foamed CPC, cellular degradation of the foams was considerably increased and accompanied by new bone formation. The additional functionalization with soybean extract in the SG-foam slightly reduced the degradation rate and positively influenced bone formation in the defect. Furthermore, both foams exhibited excellent biocompatibility, implying that these novel materials may be promising for clinical application in non-loaded bone defects. PMID:25448348

  4. Controlled Drug Release from Pharmaceutical Nanocarriers

    PubMed Central

    Lee, Jinhyun Hannah; Yeo, Yoon

    2014-01-01

    Nanocarriers providing spatiotemporal control of drug release contribute to reducing toxicity and improving therapeutic efficacy of a drug. On the other hand, nanocarriers face unique challenges in controlling drug release kinetics, due to the large surface area per volume ratio and the short diffusion distance. To develop nanocarriers with desirable release kinetics for target applications, it is important to understand the mechanisms by which a carrier retains and releases a drug, the effects of composition and morphology of the carrier on the drug release kinetics, and current techniques for preparation and modification of nanocarriers. This review provides an overview of drug release mechanisms and various nanocarriers with a specific emphasis on approaches to control the drug release kinetics. PMID:25684779

  5. A novel gelatin-based micro-cavitary hydrogel for potential application in delivery of anchorage dependent cells: A study with vasculogenesis model.

    PubMed

    Leong, Wenyan; Fan, Changjiang; Wang, Dong-An

    2016-10-01

    Hydrogels have been widely regarded as promising tissue engineering scaffolds and cell delivery vehicles, however, their inherent submicron- or nano-scale polymer networks severely inhibit the settlement of anchorage dependent cells (ADCs). Here, using endothelial progenitor outgrowth cells (EPOCs) as the typical ADCs, a gelatin-based micro-cavitary gel (namely Gel-MCG) is developed with gelatin-methacrylate and gelatin microspheres as precursor and porogens, respectively, to promote cellular focal adhesion and functions. The introduction of micro-cavitary structures within the Gel-MCG improves its physical properties as well as creates numerous gel-microcavity interfaces within gel-based matrices. Compared with conventional gelatin gel (Gel-G) scaffold, the Gel-MCG provides more suitable microenvironments for EPOCs' attachment, spreading, and proliferation, and then which leads to enhanced endothelial differentiation and vascularization as demonstrated by higher expressions of endothelial markers. The Gel-MCG system shows great potential as vehicle for the delivery of ADCs in tissue engineering. PMID:27371893

  6. Molecular engineering of high affinity single-chain antibody fragment for endothelial targeting of proteins and nanocarriers in rodents and humans.

    PubMed

    Greineder, Colin F; Hood, Elizabeth D; Yao, Anning; Khoshnejad, Makan; Brenner, Jake S; Johnston, Ian H; Poncz, Mortimer; Gottstein, Claudia; Muzykantov, Vladimir R

    2016-03-28

    Endothelial cells (EC) represent an important target for pharmacologic intervention, given their central role in a wide variety of human pathophysiologic processes. Studies in lab animal species have established that conjugation of drugs and carriers with antibodies directed to surface targets like the Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1, a highly expressed endothelial transmembrane protein) help to achieve specific therapeutic interventions in ECs. To translate such "vascular immunotargeting" to clinical practice, it is necessary to replace antibodies by advanced ligands that are more amenable to use in humans. We report the molecular design of a single chain variable antibody fragment (scFv) that binds with high affinity to human PECAM-1 and cross-reacts with its counterpart in rats and other animal species, allowing parallel testing in vivo and in human endothelial cells in microfluidic model. Site-specific modification of the scFv allows conjugation of protein cargo and liposomes, enabling their endothelial targeting in these models. This study provides a template for molecular engineering of ligands, enabling studies of drug targeting in animal species and subsequent use in humans. PMID:26855052

  7. Physical properties of fish gelatin-based bio-nanocomposite films incorporated with ZnO nanorods

    PubMed Central

    2013-01-01

    Well-dispersed fish gelatin-based nanocomposites were prepared by adding ZnO nanorods (NRs) as fillers to aqueous gelatin. The effects of ZnO NR fillers on the mechanical, optical, and electrical properties of fish gelatin bio-nanocomposite films were investigated. Results showed an increase in Young's modulus and tensile strength of 42% and 25% for nanocomposites incorporated with 5% ZnO NRs, respectively, compared with unfilled gelatin-based films. UV transmission decreased to zero with the addition of a small amount of ZnO NRs in the biopolymer matrix. X-ray diffraction showed an increase in the intensity of the crystal facets of (10ī1) and (0002) with the addition of ZnO NRs in the biocomposite matrix. The surface topography of the fish gelatin films indicated an increase in surface roughness with increasing ZnO NR concentrations. The conductivity of the films also significantly increased with the addition of ZnO NRs. These results indicated that bio-nanocomposites based on ZnO NRs had great potentials for applications in packaging technology, food preservation, and UV-shielding systems. PMID:23981366

  8. Polymer nanocarriers for dentin adhesion.

    PubMed

    Osorio, R; Osorio, E; Medina-Castillo, A L; Toledano, M

    2014-12-01

    To obtain more durable adhesion to dentin, and to protect collagen fibrils of the dentin matrix from degradation, calcium- and phosphate-releasing particles have been incorporated into the dental adhesive procedure. The aim of the present study was to incorporate zinc-loaded polymeric nanocarriers into a dental adhesive system to facilitate inhibition of matrix metalloproteinases (MMPs)-mediated collagen degradation and to provide calcium ions for mineral deposition within the resin-dentin bonded interface. PolymP- N : Active nanoparticles (nanoMyP) were zinc-loaded through 30-minute ZnCl2 immersion and tested for bioactivity by means of 7 days' immersion in simulated body fluid solution (the Kokubo test). Zinc-loading and calcium phosphate depositions were examined by scanning and transmission electron microscopy, elemental analysis, and x-ray diffraction. Nanoparticles in ethanol solution infiltrated into phosphoric-acid-etched human dentin and Single Bond (3M/ESPE) were applied to determine whether the nanoparticles interfered with bonding. Debonded sticks were analyzed by scanning electron microscopy. A metalloproteinase collagen degradation assay was also performed in resin-infiltrated dentin with and without nanoparticles, measuring C-terminal telopeptide of type I collagen (ICTP) concentration in supernatants, after 4 wk of immersion in artificial saliva. Numerical data were analyzed by analysis of variance (ANOVA) and Student-Newman-Keuls multiple comparisons tests (p < .05). Nanoparticles were effectively zinc-loaded and were shown to have a chelating effect, retaining calcium regardless of zinc incorporation. Nanoparticles failed to infiltrate demineralized intertubular dentin and remained on top of the hybrid layer, without altering bond strength. Calcium and phosphorus were found covering nanoparticles at the hybrid layer, after 24 h. Nanoparticle application in etched dentin also reduced MMP-mediated collagen degradation. Tested nanoparticles may be

  9. Polymer Nanocarriers for Dentin Adhesion

    PubMed Central

    Osorio, R.; Osorio, E.; Medina-Castillo, A.L.; Toledano, M.

    2014-01-01

    To obtain more durable adhesion to dentin, and to protect collagen fibrils of the dentin matrix from degradation, calcium- and phosphate-releasing particles have been incorporated into the dental adhesive procedure. The aim of the present study was to incorporate zinc-loaded polymeric nanocarriers into a dental adhesive system to facilitate inhibition of matrix metalloproteinases (MMPs)-mediated collagen degradation and to provide calcium ions for mineral deposition within the resin-dentin bonded interface. PolymP-nActive nanoparticles (nanoMyP) were zinc-loaded through 30-minute ZnCl2 immersion and tested for bioactivity by means of 7 days’ immersion in simulated body fluid solution (the Kokubo test). Zinc-loading and calcium phosphate depositions were examined by scanning and transmission electron microscopy, elemental analysis, and x-ray diffraction. Nanoparticles in ethanol solution infiltrated into phosphoric-acid-etched human dentin and Single Bond (3M/ESPE) were applied to determine whether the nanoparticles interfered with bonding. Debonded sticks were analyzed by scanning electron microscopy. A metalloproteinase collagen degradation assay was also performed in resin-infiltrated dentin with and without nanoparticles, measuring C-terminal telopeptide of type I collagen (ICTP) concentration in supernatants, after 4 wk of immersion in artificial saliva. Numerical data were analyzed by analysis of variance (ANOVA) and Student-Newman-Keuls multiple comparisons tests (p < .05). Nanoparticles were effectively zinc-loaded and were shown to have a chelating effect, retaining calcium regardless of zinc incorporation. Nanoparticles failed to infiltrate demineralized intertubular dentin and remained on top of the hybrid layer, without altering bond strength. Calcium and phosphorus were found covering nanoparticles at the hybrid layer, after 24 h. Nanoparticle application in etched dentin also reduced MMP-mediated collagen degradation. Tested nanoparticles may be

  10. Nanocarriers for spleen targeting: anatomo-physiological considerations, formulation strategies and therapeutic potential.

    PubMed

    Jindal, Anil B

    2016-10-01

    There are several clinical advantages of spleen targeting of nanocarriers. For example, enhanced splenic concentration of active agents could provide therapeutic benefits in spleen resident infections and hematological disorders including malaria, hairy cell leukemia, idiopathic thrombocytopenic purpura, and autoimmune hemolytic anemia. Furthermore, spleen delivery of immunosuppressant agents using splenotropic carriers may reduce the chances of allograft rejection in organ transplantation. Enhanced concentration of radiopharmaceuticals in the spleen may improve visualization of the organ, which could provide benefit in the diagnosis of splenic disorders. Unique anatomical features of the spleen including specialized microvasculature environment and slow blood circulation rate enable it an ideal drug delivery site. Because there is a difference in blood flow between spleen and liver, splenic delivery is inversely proportional to the hepatic uptake. It is therefore desirable engineering of nanocarriers, which, upon intravenous administration, can avoid uptake by hepatic Kupffer cells to enhance splenic localization. Stealth and non-spherical nanocarriers have shown enhanced splenic delivery of active agents by avoiding hepatic uptake. The present review details the research in the field of splenotropy. Formulation strategies to design splenotropic drug delivery systems are discussed. The review also highlights the clinical relevance of spleen targeting of nanocarriers and application in diagnostics. PMID:27334277

  11. Photo and Redox Dual Responsive Reversibly Cross-Linked Nanocarrier for Efficient Tumor-Targeted Drug Delivery

    PubMed Central

    2015-01-01

    To develop a feasible and efficient nanocarrier for potential clinical application, a series of photo and redox dual responsive reversibly cross-linked micelles have been developed for the targeted anticancer drug delivery. The nanocarrier can be cross-linked efficiently via a clean, efficient, and controllable coumarin photodimerization within the nanocarrier, which simplify the formulation process and quality control prior clinical use and improve the in vivo stability for tumor targeting. At the same time, cross-linking of nanocarrier could be cleaved via the responsiveness of the built-in disulfide cross-linkage to the redox tumor microenvironment for on-demand drug release. Coumarin and disulfide bond was introduced into a linear-dendritic copolymer (named as telodendrimer) precisely via peptide chemistry. The engineered nanocarrier possesses good drug loading capacity and stability, and exhibits a safer profile as well as similar anticancer effects compared with free drug in cell culture. The in vivo and ex vivo small animal imaging revealed the preferred tumor accumulation and the prolonged tumor residency of the payload delivered by the cross-linked micelles compared to the non-cross-linked micelles and free drug surrogate because of the increased stability. PMID:24921150

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

    PubMed Central

    2013-01-01

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

  13. Surface modification of nonviral nanocarriers for enhanced gene delivery.

    PubMed

    Fortier, Charles; Durocher, Yves; De Crescenzo, Gregory

    2014-01-01

    Biomedical nanotechnology has given a new lease of life to gene therapy with the ever-developing and ever-diversifying nonviral gene delivery nanocarriers. These are designed to pass a series of barriers in order to bring their nucleic acid cargo to the right subcellular location of particular cells. For a given application, each barrier has its dedicated strategy, which translates into a physicochemical, biological and temporal identity of the nanocarrier surface. Different strategies have thus been explored to implement adequate surface identities on nanocarriers over time for systemic delivery. In that context, this review will mainly focus on organic nanocarriers, for which these strategies will be described and discussed. PMID:24354815

  14. Lipid-Based Nanocarriers for RNA Delivery.

    PubMed

    Xue, Hui Yi; Guo, Pengbo; Wen, Wu-Cheng; Wong, Ho Lun

    2015-01-01

    RNA-interference (RNAi) agents such as small-interfering RNA (siRNA) and micro-RNA (miRNA) have strong potential as therapeutic agents for the treatment of a broad range of diseases such as malignancies, infections, autoimmune diseases and neurological diseases that are associated with undesirable gene expression. In recent years, several clinical trials of RNAi therapeutics especially siRNAs have been conducted with limited success so far. For systemic administration of these poorly permeable and easily degradable macromolecules, it is obvious that a safe and efficient delivery platform is highly desirable. Because of high biocompatibility, biodegradability and solid track record for clinical use, nanocarriers made of lipids and/or phospholipids have been commonly employed to facilitate RNA delivery. In this article, the key features of the major sub-classes of lipid-based nanocarriers, e.g. liposomes, lipid nanoparticles and lipid nanoemulsions, will be reviewed. Focus of the discussion is on the various challenges researchers face when developing lipid-based RNA nanocarriers, such as the toxicity of cationic lipids and issues related to PEGylated lipids, as well as the strategies employed in tackling these challenges. It is hoped that by understanding more about the pros and cons of these most frequently used RNA delivery systems, the pharmaceutical scientists, biomedical researchers and clinicians will be more successful in overcoming some of the obstacles that currently limit the clinical translation of RNAi therapy. PMID:26027572

  15. Lipid-Based Nanocarriers for RNA Delivery

    PubMed Central

    Xue, Hui Yi; Guo, Pengbo; Wen, Wu-Cheng; Wong, Ho Lun

    2015-01-01

    RNA-interference (RNAi) agents such as small-interfering RNA (siRNA) and micro-RNA (miRNA) have strong potential as therapeutic agents for the treatment of a broad range of diseases such as malignancies, infections, autoimmune diseases and neurological diseases that are associated with undesirable gene expression. In recent years, several clinical trials of RNAi therapeutics especially siRNAs have been conducted with limited success so far. For systemic administration of these poorly permeable and easily degradable macromolecules, it is obvious that a safe and efficient delivery platform is highly desirable. Because of high biocompatibility, biodegradability and solid track record for clinical use, nanocarriers made of lipids and/or phospholipids have been commonly employed to facilitate RNA delivery. In this article, the key features of the major sub-classes of lipid-based nanocarriers, e.g. liposomes, lipid nanoparticles and lipid nanoemulsions, will be reviewed. Focus of the discussion is on the various challenges researchers face when developing lipid-based RNA nanocarriers, such as the toxicity of cationic lipids and issues related to PEGylated lipids, as well as the strategies employed in tackling these challenges. It is hoped that by understanding more about the pros and cons of these most frequently used RNA delivery systems, the pharmaceutical scientists, biomedical researchers and clinicians will be more successful in overcoming some of the obstacles that currently limit the clinical translation of RNAi therapy. PMID:26027572

  16. A drug-specific nanocarrier design for efficient anticancer therapy

    NASA Astrophysics Data System (ADS)

    Shi, Changying; Guo, Dandan; Xiao, Kai; Wang, Xu; Wang, Lili; Luo, Juntao

    2015-07-01

    The drug-loading properties of nanocarriers depend on the chemical structures and properties of their building blocks. Here we customize telodendrimers (linear dendritic copolymer) to design a nanocarrier with improved in vivo drug delivery characteristics. We do a virtual screen of a library of small molecules to identify the optimal building blocks for precise telodendrimer synthesis using peptide chemistry. With rationally designed telodendrimer architectures, we then optimize the drug-binding affinity of a nanocarrier by introducing an optimal drug-binding molecule (DBM) without sacrificing the stability of the nanocarrier. To validate the computational predictions, we synthesize a series of nanocarriers and evaluate systematically for doxorubicin delivery. Rhein-containing nanocarriers have sustained drug release, prolonged circulation, increased tolerated dose, reduced toxicity, effective tumour targeting and superior anticancer effects owing to favourable doxorubicin-binding affinity and improved nanoparticle stability. This study demonstrates the feasibility and versatility of the de novo design of telodendrimer nanocarriers for specific drug molecules, which is a promising approach to transform nanocarrier development for drug delivery.

  17. A drug-specific nanocarrier design for efficient anticancer therapy

    PubMed Central

    Shi, Changying; Guo, Dandan; Xiao, Kai; Wang, Xu; Wang, Lili; Luo, Juntao

    2015-01-01

    The drug-loading properties of nanocarriers depend on the chemical structures and properties of their building blocks. Here, we customize telodendrimers (linear-dendritic copolymer) to design a nanocarrier with improved in vivo drug delivery characteristics. We do a virtual screen of a library of small molecules to identify the optimal building blocks for precise telodendrimer synthesis using peptide chemistry. With rationally designed telodendrimer architectures, we then optimize the drug binding affinity of a nanocarrier by introducing an optimal drug-binding molecule (DBM) without sacrificing the stability of the nanocarrier. To validate the computational predictions, we synthesize a series of nanocarriers and evaluate systematically for doxorubicin delivery. Rhein-containing nanocarriers have sustained drug release, prolonged circulation, increased tolerated dose, reduced toxicity, effective tumor targeting and superior anticancer effects owing to favourable doxorubicin-binding affinity and improved nanoparticle stability. This study demonstrates the feasibility and versatility of the de novo design of telodendrimer nanocarriers for specific drug molecules, which is a promising approach to transform nanocarrier development for drug delivery. PMID:26158623

  18. Utilising inorganic nanocarriers for gene delivery.

    PubMed

    Loh, Xian Jun; Lee, Tung-Chun; Dou, Qingqing; Deen, G Roshan

    2016-01-01

    The delivery of genetic materials into cells to elicit cellular responses has been extensively studied by biomaterials scientists globally. Many materials such as lipids, peptides, viruses, synthetically modified cationic polymers and certain inorganic nanomaterials could be used to complex the negatively charged plasmids and deliver the formed package into cells. The recent literature on the delivery of genetic materials utilising inorganic nanoparticles is carefully examined in this review. We have picked out the most relevant references and concisely summarised the findings with illustrated examples. We further propose alternative approaches and suggest future pathways towards the practical use of multifunctional nanocarriers. PMID:26484365

  19. Mechanical, physico-chemical, and antimicrobial properties of gelatin-based film incorporated with catechin-lysozyme

    PubMed Central

    2012-01-01

    Background Microbial activity is a primary cause of deterioration in many foods and is often responsible for reduced quality and safety. Food-borne illnesses associated with E. coli O157:H7, S. aureus, S. enteritidis and L. monocytogenes are a major public health concern throughout the world. A number of methods have been employed to control or prevent the growth of these microorganisms in food. Antimicrobial packaging is one of the most promising active packaging systems for effectively retarding the growth of food spoilage and pathogenic microorganisms. The aim of this study was to determine the mechanical, physico-chemical properties and inhibitory effects of the fish gelatin films against selected food spoilage microorganisms when incorporated with catechin-lysozyme. Results The effect of the catechin-lysozyme combination addition (CLC: 0, 0.125, 0.25, and 0.5%, w/v) on fish gelatin film properties was monitored. At the level of 0.5% addition, the CLC showed the greatest elongation at break (EAB) at 143.17% with 0.039 mm thickness, and the lowest water vapor permeability (WVP) at 6.5 x 10−8 g·mm·h-1·cm-2·Pa-1, whereas the control showed high tensile strength (TS) and the highest WVP. Regarding color attributes, the gelatin film without CLC addition gave the highest lightness (L* 91.95) but lowest in redness (a*-1.29) and yellowness (b* 2.25) values. The light transmission of the film did not significantly decrease and nor did film transparency (p>0.05) with increased CLC. Incorporating CLC could not affect the film microstructure. The solubility of the gelatin based film incorporated with CLC was not affected, especially at a high level of addition (p>0.05). Inhibitory activity of the fish gelatin film against E.coli, S.aureus, L. innocua and S. cerevisiae was concentration dependent. Conclusions These findings suggested that CLC incorporation can improve mechanical, physico-chemical, and antimicrobial properties of the resulting films, thus allowing the

  20. Fucose decorated solid-lipid nanocarriers mediate efficient delivery of methotrexate in breast cancer therapeutics.

    PubMed

    Garg, Neeraj K; Singh, Bhupinder; Jain, Ashay; Nirbhavane, Pradip; Sharma, Rajeev; Tyagi, Rajeev K; Kushwah, Varun; Jain, Sanyog; Katare, Om Prakash

    2016-10-01

    The present study is designed to engineer fucose anchored methotrexate loaded solid lipid nanoparticles (SLNs) to target breast cancer. The developed nano-carriers were characterized with respect to particle size, PDI, zeta potential, drug loading and entrapment, in-vitro release etc. The characterized formulations were used to comparatively assess cellular uptake, cell-viability, apoptosis, lysosomal membrane permeability, bioavailability, biodistribution, changes in tumor volume and animal survival. The ex-vivo results showed greater cellular uptake and better cytotoxicity at lower IC50 of methotrexate in breast cancer cells. Further, we observed increased programmed cell death (apoptosis) with altered lysosomal membrane permeability and better rate of degradation of lysosomal membrane in-vitro. On the other hand, in-vivo evaluation showed maximum bioavailability and tumor targeting efficiency with minimum secondary drug distribution in various organs with formulated and anchored nano-carrier when compared with free drug. Moreover, sizeable reduction in tumor burden was estimated with fucose decorated SLNs as compared to that seen with free MTX and SLNs-MTX. Fucose decorated SLNs showed promising results to develop therapeutic interventions for breast cancer, and paved a way to explore this promising and novel nano-carrier which enables to address breast cancer. PMID:27268228

  1. How successful is nuclear targeting by nanocarriers?

    PubMed

    Tammam, Salma N; Azzazy, Hassan M E; Lamprecht, Alf

    2016-05-10

    The nucleus is ultimately the final target for many therapeutics treating various disorders including cancers, heart dysfunction and brain disorders. Owing to their specialized cell uptake and trafficking mechanisms, nanoparticles (NPs) allow drug targeting where degradation sensitive therapeutics could be delivered to their target tissues and cell in active form and sufficient concentration. However, it has recently become increasingly obvious that cytosolic internalization of a drug molecule does not entail its interaction with its subcellular target and hence careful nanoparticle design and optimization is required to enable nuclear targeting. This review, discusses the barriers to NP nuclear delivery; crossing the cell membrane, endo/lysosomal escape, cytoplasmic trafficking and finally nuclear entry focusing on how NP synthesis and modification could allow for bypassing each of the aforementioned barriers and successfully reaching the nucleus. Examples of nuclear targeted NPs are also discussed, stressing on the critical aspects of nuclear targeting and pointing out how the disease state might change the normal NP path and how such change could be exploited to increase efficiency of nuclear targeting. Finally, the criteria set for the evaluation of nanocarriers for nuclear delivery are discussed highlighting that quantitative rather than qualitative evaluation is required to evaluate how successful nanocarriers for nuclear delivery are, particularly with regards to the amount of drug delivered and released in the nucleus. PMID:26995759

  2. Ultrasound-Mediated Local Drug and Gene Delivery Using Nanocarriers

    PubMed Central

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

    2014-01-01

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

  3. Design and Application of Multifunctional DNA Nanocarriers for Therapeutic Delivery

    PubMed Central

    Charoenphol, Phapanin; Bermudez, Harry

    2013-01-01

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

  4. Nanocarriers of nanotechnology in retinal diseases.

    PubMed

    Al-Halafi, Ali M

    2014-10-01

    We are approaching a new era of retinal pharmacotherapy where new drugs are rapidly being worked out for the treatment of posterior-segment disease. Recent development in ocular drug delivery systems research has provided new insights into drug development, and the use of nanoparticles for drug delivery is thus a promising excellent approach for advanced therapy of ocular diseases. The primary goal is to develop a variety of drug delivery systems to complement and further enhance the efficacy of the available new medications. The ideal sustained release technology will provide a high level of safety with continuous release over an extended period of time while maintaining almost total drug bioactivity. The use of nanocarriers, such as cyclodextrin nanoparticle suspension, liposomes, nanospheres and, nanoemulsions for gene therapy of retinal diseases has been highlighted in this review. PMID:25473348

  5. Nanocarriers for delivery of platinum anticancer drugs☆

    PubMed Central

    Oberoi, Hardeep S.; Nukolova, Natalia V.; Kabanov, Alexander V.; Bronich, Tatiana K.

    2014-01-01

    Platinum based anticancer drugs have revolutionized cancer chemotherapy, and continue to be in widespread clinical use especially for management of tumors of the ovary, testes, and the head and neck. However, several dose limiting toxicities associated with platinum drug use, partial anti-tumor response in most patients, development of drug resistance, tumor relapse, and many other challenges have severely limited the patient quality of life. These limitations have motivated an extensive research effort towards development of new strategies for improving platinum therapy. Nanocarrier-based delivery of platinum compounds is one such area of intense research effort beginning to provide encouraging preclinical and clinical results and may allow the development of the next generation of platinum chemotherapy. This review highlights current understanding on the pharmacology and limitations of platinum compounds in clinical use, and provides a comprehensive analysis of various platinum–polymer complexes, micelles, dendrimers, liposomes and other nanoparticles currently under investigation for delivery of platinum drugs. PMID:24113520

  6. On the synthesis of mucus permeating nanocarriers.

    PubMed

    Bourganis, Vassilis; Karamanidou, Theodora; Samaridou, Eleni; Karidi, Konstantina; Kammona, Olga; Kiparissides, Costas

    2015-11-01

    The synthesis of nanocarriers with "slippery" surface (i.e., poly(lactide-co-glycolide)-polyethylene glycol (PLGA-PEG) nanoparticles (NPs) and polyelectrolyte complexes (PECs) of polyacrylic acid (PAA) with poly-L-lysine (PLL) and/or polyarginine (PArg)) and of nanocarriers (i.e., PLGA NPs, PLGA-PEG NPs, liposomes) containing a mucolytic agent (i.e., 4-mercaptobenzoic acid (4MBA)) is presented. Depending on the molecular weight (MW) of PEG (i.e., 2, 5 kDa), PLGA-PEG NPs with a "brush" or "dense brush" PEG configuration were prepared. The PLGA-PEG NPs exhibited increased mucus permeability in comparison with non-pegylated PLGA NPs when tested in fresh porcine intestinal mucus. The NPs that were prepared using PEG with a MW equal to 5 kDa and had a "dense brush" PEG configuration, were found to exhibit the highest mucus permeability. The average size and the surface charge of PECs could be effectively tuned by varying the PAA/polycation charge ratio, thus resulting in the synthesis of neutral as well as positively and negatively charged PECs. The PECs with negative surface charges were found to exhibit the highest mucus permeability followed by the neutral and finally the positively charged PECs. Depending on the initial concentration of the mucolytic agent, 4MBA loadings up to 13.65, 13.1 and 18.43 wt% were achieved for PLGA NPs, PLGA-PEG NPs and liposomes, respectively. PLGA and PLGA-PEG NPs were characterized by a rapid release of the mucolytic agent (i.e., >80 wt% of 4MBA was released in 20 min) whereas, its encapsulation in liposomes allowed a more controlled release (i.e., up to 30 wt% of 4MBA was released in 45 min). 4MBA loaded liposomes were found to exhibit increased mucus permeability depending on the composition of the phospholipid bilayer. PMID:25661586

  7. Multifunctional Liposome Nanocarriers Combining Upconverting Nanoparticles and Anticancer Drugs.

    PubMed

    Huang, Yue; Hemmer, Eva; Rosei, Federico; Vetrone, Fiorenzo

    2016-06-01

    Lanthanide-doped upconverting nanoparticles (UCNPs) are well-known for their inherent ability to convert low energy near-infrared (NIR) excitation wavelengths into higher energy emission wavelengths covering the ultraviolet (UV) to NIR regions. This optical feature makes UCNPs highly attractive for a broad range of applications including (bio)imaging and the biomedical use of light-triggered processes such as drug release. In the quest for novel theranostic approaches, the combination of multiple modalities on a single nanoscale platform, for example, combining optical imaging and drug delivery, is very desirable. In this context, liposomes, artificially prepared constructs composed of a lamellar phase lipid bilayer, have been introduced as suitable nanocarriers for UCNPs. Here, we developed a hybrid nanocarrier consisting of Er(3+) and Yb(3+) co-doped NaGdF4 UCNPs that were encapsulated in the aqueous core of the liposomes and the potential of the obtained nanocarriers for drug delivery was shown by co-loading the model anticancer drug doxorubicin (DOX). Under 980 nm excitation, a decrease of the green upconversion emission of the NaGdF4:Er(3+), Yb(3+) UCNPs was observed when DOX was co-loaded with the UCNPs in the liposome nanocarrier. This quenching effect is assigned to the energy transfer between the donor UCNP and the acceptor DOX and is most significant, since it allows for the spectral monitoring of the DOX loading and release from the liposome nanocarriers. Thus, the drug loading, release, and spectral monitoring properties of the obtained liposome nanocarriers were thoroughly characterized allowing us to assess their future potential as theranostic nanocarriers. PMID:27135855

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

    PubMed Central

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

    2016-01-01

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

  9. Shaping Nanoparticles with Hydrophilic Compositions and Hydrophobic Properties as Nanocarriers for Antibiotic Delivery.

    PubMed

    Ahmad Nor, Yusilawati; Niu, Yuting; Karmakar, Surajit; Zhou, Liang; Xu, Chun; Zhang, Jun; Zhang, Hongwei; Yu, Meihua; Mahony, Donna; Mitter, Neena; Cooper, Matthew A; Yu, Chengzhong

    2015-09-23

    Inspired by the lotus effect in nature, surface roughness engineering has led to novel materials and applications in many fields. Despite the rapid progress in superhydrophobic and superoleophobic materials, this concept of Mother Nature's choice is yet to be applied in the design of advanced nanocarriers for drug delivery. Pioneering work has emerged in the development of nanoparticles with rough surfaces for gene delivery; however, the preparation of nanoparticles with hydrophilic compositions but with enhanced hydrophobic property at the nanoscale level employing surface topology engineering remains a challenge. Herein we report for the first time the unique properties of mesoporous hollow silica (MHS) nanospheres with controlled surface roughness. Compared to MHS with a smooth surface, rough mesoporous hollow silica (RMHS) nanoparticles with the same hydrophilic composition show unusual hydrophobicity, leading to higher adsorption of a range of hydrophobic molecules and controlled release of hydrophilic molecules. RMHS loaded with vancomycin exhibits an enhanced antibacterial effect. Our strategy provides a new pathway in the design of novel nanocarriers for diverse bioapplications. PMID:27162988

  10. Shaping Nanoparticles with Hydrophilic Compositions and Hydrophobic Properties as Nanocarriers for Antibiotic Delivery

    PubMed Central

    2015-01-01

    Inspired by the lotus effect in nature, surface roughness engineering has led to novel materials and applications in many fields. Despite the rapid progress in superhydrophobic and superoleophobic materials, this concept of Mother Nature’s choice is yet to be applied in the design of advanced nanocarriers for drug delivery. Pioneering work has emerged in the development of nanoparticles with rough surfaces for gene delivery; however, the preparation of nanoparticles with hydrophilic compositions but with enhanced hydrophobic property at the nanoscale level employing surface topology engineering remains a challenge. Herein we report for the first time the unique properties of mesoporous hollow silica (MHS) nanospheres with controlled surface roughness. Compared to MHS with a smooth surface, rough mesoporous hollow silica (RMHS) nanoparticles with the same hydrophilic composition show unusual hydrophobicity, leading to higher adsorption of a range of hydrophobic molecules and controlled release of hydrophilic molecules. RMHS loaded with vancomycin exhibits an enhanced antibacterial effect. Our strategy provides a new pathway in the design of novel nanocarriers for diverse bioapplications. PMID:27162988

  11. Supramolecular cyclodextrin-based drug nanocarriers.

    PubMed

    Simões, Susana M N; Rey-Rico, Ana; Concheiro, Angel; Alvarez-Lorenzo, Carmen

    2015-04-14

    Supramolecular systems formed by the binding of several cyclodextrins (CDs) to polymers or lipids, either via non-covalent or covalent links, open a wide range of possibilities for the delivery of active substances. CDs can perform as multifunctionalizable cores to which very diverse (macro)molecules and drugs can be conjugated. Grafting with amphiphilic molecules can lead to nanoassemblies exhibiting a variety of architectures. CDs can also polymerize with other CDs or can be used to functionalize preexisting polymers to form polymers/networks with enhanced capability to form inclusion complexes. Alternatively, CDs can be exploited as transient cross-linkers to form poly(pseudo)rotaxane-based networks or zipper-like assemblies. Combination of mutifunctionality and complexation ability of CDs has been shown to be useful to develop depot-like formulations and colloidal nanocarriers with improved performances regarding easiness of administration, protection of the encapsulated substances, control of the delivery rate, and cell interactions. The aim of this review is to provide an overall view of the diversity of designs of CD-based supramolecular nanosystems with a special focus on the advances materialized in the last five years, including clinical trials. PMID:25679097

  12. Novel nanocarrier for oral Hepatitis B vaccine.

    PubMed

    Dinda, Amit K; Bhat, Madhusudan; Srivastava, Sandeep; Kottarath, Sarat K; Prashant, Chandravilas K

    2016-06-01

    Oral vaccination is a safe, cost effective and non-invasive method suitable for mass immunization. We fabricated nanoparticle (NP) with 14kd polycaprolactone (PCL) entrapping hepatitis B surface antigen (HBsAg) stabilized with Pluronics® F127 and used it as oral delivery vehicle. We evaluated its efficacy for specific antibody production and compared with parenteral routes of immunization in mice. We found a superior antibody response with a higher titer of anti-HBsAg antibody till 2 months following single oral administration compared to other routes of immunization and conventional alum-based HBsAg vaccine. The NPs with the antigen were found in the macrophages in small intestinal villi, peripheral lymph nodes and other reticulo-endothelial organs 2 months after oral administration. This study suggests the efficacy of the current nanocarrier system for efficient antigen presentation disseminated in peripheral lymphoid tissues following oral administration with a prolonged antibody response, which can minimize the requirement of booster dose. PMID:27156634

  13. Recent Developments of Liposomes as Nanocarriers for Theranostic Applications

    PubMed Central

    Xing, Hang; Hwang, Kevin; Lu, Yi

    2016-01-01

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

  14. Mucus barrier-triggered disassembly of siRNA nanocarriers

    NASA Astrophysics Data System (ADS)

    Thomsen, Troels B.; Li, Leon; Howard, Kenneth A.

    2014-10-01

    The mucus overlying mucosal epithelial surfaces presents not only a biological barrier to the penetration of potential pathogens, but also therapeutic modalities including RNAi-based nanocarriers. Movement of nanomedicines across the mucus barriers of the gastrointestinal mucosa is modulated by interactions of the nanomedicine carriers with mucin glycoproteins inside the mucus, potentiated by the large surface area of the nanocarrier. We have developed a fluorescence activation-based reporter system showing that the interaction between polyanionic mucins and the cationic chitosan/small interfering RNA (siRNA) nanocarriers (polyplexes) results in the disassembly and consequent triggered release of fluorescent siRNA. The quantity of release was found to be dependent on the molar ratio between chitosan amino groups and siRNA phosphate groups (NP ratio) of the polyplexes with a maximal estimated 48.6% release of siRNA over 30 min at NP 60. Furthermore, a microfluidic in vitro model of the gastrointestinal mucus barrier was used to visualize the dynamic interaction between chitosan/siRNA nanocarriers and native purified porcine stomach mucins. We observed strong interactions and aggregations at the mucin-liquid interface, followed by an NP ratio dependent release and consequent diffusion of siRNA across the mucin barrier. This work describes a new model of interaction at the nanocarrier-mucin interface and has important implications for the design and development of nucleic acid-based nanocarrier therapeutics for mucosal disease treatments and also provides insights into nanoscale pathogenic processes.The mucus overlying mucosal epithelial surfaces presents not only a biological barrier to the penetration of potential pathogens, but also therapeutic modalities including RNAi-based nanocarriers. Movement of nanomedicines across the mucus barriers of the gastrointestinal mucosa is modulated by interactions of the nanomedicine carriers with mucin glycoproteins inside the

  15. Nanocarriers in therapy of infectious and inflammatory diseases

    NASA Astrophysics Data System (ADS)

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

    2015-02-01

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

  16. Assessing biocompatibility of graphene oxide-based nanocarriers: A review.

    PubMed

    Kiew, Siaw Fui; Kiew, Lik Voon; Lee, Hong Boon; Imae, Toyoko; Chung, Lip Yong

    2016-03-28

    Graphene oxide (GO)-based nanocarriers have been frequently studied due to their high drug loading capacity. However, the unsatisfactory biocompatibility of these GO-based nanocarriers hampers their use in clinical settings. This review discusses how each of the physicochemical characteristics (e.g., size, surface area, surface properties, number of layers and particulate states) and surface coatings on GO affect its in vitro and in vivo nanotoxicity. We provide an overview on the effect of GO properties on interactions with cells such as red blood cells, macrophages and cell lines, and experimental organisms including rodents, rabbits and Zebrafish, offering some guidelines for development of safe GO-based nanocarriers. We conclude the paper by outlining the challenges involving GO-based formulations and future perspectives of this research in the biomedical field. PMID:26873333

  17. Lipid prodrug nanocarriers in cancer therapy.

    PubMed

    Mura, Simona; Bui, Duc Trung; Couvreur, Patrick; Nicolas, Julien

    2015-06-28

    Application of nanotechnology in the medical field (i.e., nanomedicine) plays an important role in the development of novel drug delivery methods. Nanoscale drug delivery systems can indeed be customized with specific functionalities in order to improve the efficacy of the treatments. However, despite the progresses of the last decades, nanomedicines still face important obstacles related to: (i) the physico-chemical properties of the drug moieties which may reduce the total amount of loaded drug; (ii) the rapid and uncontrolled release (i.e., burst release) of the encapsulated drug after administration and (iii) the instability of the drug in biological media where a fast transformation into inactive metabolites can occur. As an alternative strategy to alleviate these drawbacks, the prodrug approach has found wide application. The covalent modification of a drug molecule into an inactive precursor from which the drug will be freed after administration offers several benefits such as: (i) a sustained drug release (mediated by chemical or enzymatic hydrolysis of the linkage between the drug-moiety and its promoiety); (ii) an increase of the drug chemical stability and solubility and, (iii) a reduced toxicity before the metabolization occurs. Lipids have been widely used as building blocks for the design of various prodrugs. Interestingly enough, these lipid-derivatized drugs can be delivered through a nanoparticulate form due to their ability to self-assemble and/or to be incorporated into lipid/polymer matrices. Among the several prodrugs developed so far, this review will focus on the main achievements in the field of lipid-based prodrug nanocarriers designed to improve the efficacy of anticancer drugs. Gemcitabine (Pubchem CID: 60750); 5-fluorouracil (Pubchem CID: 3385); Doxorubicin (Pubchem CID: 31703); Docetaxel (Pubchem CID: 148124); Methotrexate (Pubchem CID: 126941); Paclitaxel (Pubchem CID: 36314). PMID:25617724

  18. Fabrication of multi-biofunctional gelatin-based electrospun fibrous scaffolds for enhancement of osteogenesis of mesenchymal stem cells.

    PubMed

    Lin, Wei-Han; Yu, Jiashing; Chen, Guoping; Tsai, Wei-Bor

    2016-02-01

    Biofunctional scaffolds that support the adhesion, proliferation, and osteo-differentiation of mesenchymal stem cells (MSCs) are critical for bone tissue engineering. In this study, a simple in situ UV-crosslinking strategy was utilized to fabricate gelatin electrospun fibrous (GEF) scaffolds with multiple biosignals, including cell adhesive Arg-Gly-Asp (RGD) peptide, osteo-conductive hydroxyapatite (HAp) nanoparticles, and osteo-inductive bone morphogenic protein-2 (BMP-2). The adhesion and proliferation of MSCs on the GEF scaffolds were improved by the incorporation of RGD. Meanwhile, the incorporation of HAp and BMP-2 enhanced osteo-differentiation of MSCs. The three incorporated bio-factors exert a synergistic effect on osteogenesis of MSCs in the GEF scaffolds. This strategy of incorporating multiple biomolecules could be used to fabricate crosslinked electrospun scaffolds of natural polymers for tissue-engineering applications. PMID:26642073

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

    PubMed

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

    2016-01-01

    Chemotherapy for AML is hampered by severe side-effects and failure to eliminate all the blasts that eventually leads to relapse. The use of nanosized particulate drug carriers such as liposomes and polymeric nanoparticles has the potential to improve AML therapy by delivering more of the drug to the disease site, thereby reducing toxicity. For example, encapsulation in liposomes reduces the cardiotoxicity of anthracyclines, giving an improved therapeutic index. Moreover, when the surface properties are engineered appropriately, nanocarriers remain in the circulation and extravasate in tissues with sinusoidal capillaries, one of which is bone marrow, leading to a more favourable distribution of the associated drug. Drug carrier technology contributes to the development of newer drugs, such as nucleic acids that can be protected from degradation and delivered into cells, thus opening the way for gene-silencing strategies. Furthermore, carrier systems provide a means of dispersing poorly water-soluble molecule for in vivo administration and thus increase the "druggability" of new lead compounds, such as heat-shock protein inhibitors. Particulate carriers can transport more than one active agent, allowing synergistic action and theranostic strategies. Notably, phase I and II clinical trials are being performed with CPX-351, a liposomal formulation containing cytarabine and daunorubicin at an optimal ratio. Finally, by attaching suitable ligands to the nanocarrier surface, specific targeting to AML cells can be achieved. In this review, we give examples of successful targeting to folate and transferrin receptors against AML. PMID:26278525

  20. Stealth Properties to Improve Therapeutic Efficacy of Drug Nanocarriers

    PubMed Central

    Caliceti, Paolo

    2013-01-01

    Over the last few decades, nanocarriers for drug delivery have emerged as powerful tools with unquestionable potential to improve the therapeutic efficacy of anticancer drugs. Many colloidal drug delivery systems are underdevelopment to ameliorate the site specificity of drug action and reduce the systemic side effects. By virtue of their small size they can be injected intravenously and disposed into the target tissues where they release the drug. Nanocarriers interact massively with the surrounding environment, namely, endothelium vessels as well as cells and blood proteins. Consequently, they are rapidly removed from the circulation mostly by the mononuclear phagocyte system. In order to endow nanosystems with long circulation properties, new technologies aimed at the surface modification of their physicochemical features have been developed. In particular, stealth nanocarriers can be obtained by polymeric coating. In this paper, the basic concept underlining the “stealth” properties of drug nanocarriers, the parameters influencing the polymer coating performance in terms of opsonins/macrophages interaction with the colloid surface, the most commonly used materials for the coating process and the outcomes of this peculiar procedure are thoroughly discussed. PMID:23533769

  1. Nanocarriers for respiratory diseases treatment: recent advances and current challenges.

    PubMed

    Trapani, Adriana; Gioia, Sante Di; Castellani, Stefano; Carbone, Annalucia; Cavallaro, Gennara; Trapani, Giuseppe; Conese, Massimo

    2014-01-01

    Pulmonary delivery of locally-acting drugs encapsulated in nanocarriers provides several advantages for the treatment of respiratory diseases such as asthma, chronic obstructive pulmonary diseases, cystic fibrosis, tuberculosis and lung cancer. These advantages include, among others, sustained drug delivery to the lungs, reduced therapeutic dose and improved patient compliance. The aim of this review is to give an updated overview on recent advances recorded in the last few years in this field as well as on the major challenges still existing and that remain to be overcome before any clinical application. After an outline on the cellular and extracellular barriers affecting drug delivery to the airways both in physiological and pathological conditions, the significant developments recorded using inhaled polymeric- and lipid-based nanocarriers for drug and gene delivery to the lung are presented. In this discussion, the major challenges existing in the field are evidenced including the understanding of the factors governing the mucus penetration capability of these nanocarriers and the identification of new technologies for delivering drugs to specific regions or cell types of the lungs. In this regard, the recognition of receptor expressed only at lung level may facilitate drug targeting to this organ and it should improve the therapeutic efficacy of nanocarrier-based treatments for respiratory diseases. PMID:24678708

  2. Advances on Magnetic Nanocarriers Based on Natural Polymers.

    PubMed

    Muzzalupo, Rita; Tavano, Lorena

    2016-01-01

    The use of nanodevices to transport active compounds like small-molecular drugs, peptides, or genes found an increased attention throughout the different fields of natural sciences. Moreover, recent research trends are focused on the employment of smart nanocarriers able to react on certain internal or external applied stimuli, in order to achieve temporal and site-specific drugs/gene release. In contrast to traditional biodegradable nanocarriers that slowly release drugs inside the cells, these smart nanosystems are able to quickly release or even dump drugs in response to a specific biological signal in the target cancer cells such lower pH, high redox potential or over expression of enzymes or to external stimuli such as temperature, light, ultrasounds and magnetic field. This review gives a brief overview about some types of stimuli-responsive nanocarriers, with the main focus on magnetic fieldresponsive devices obtained from natural polymers. The concept of magnetic field-sensitive nanocarriers, their advantages and disadvantages, the methods of preparation and applications in various fields of drug delivery will be explored, giving an exhaustive collection of the findings of recent investigations. PMID:26861649

  3. Interaction of Human Plasma Proteins with Thin Gelatin-Based Hydrogel Films: A QCM-D and ToF-SIMS Study

    PubMed Central

    2015-01-01

    In the fields of surgery and regenerative medicine, it is crucial to understand the interactions of proteins with the biomaterials used as implants. Protein adsorption directly influences cell-material interactions in vivo and, as a result, regulates, for example, cell adhesion on the surface of the implant. Therefore, the development of suitable analytical techniques together with well-defined model systems allowing for the detection, characterization, and quantification of protein adsorbates is essential. In this study, a protocol for the deposition of highly stable, thin gelatin-based films on various substrates has been developed. The hydrogel films were characterized morphologically and chemically. Due to the obtained low thickness of the hydrogel layer, this setup allowed for a quantitative study on the interaction of human proteins (albumin and fibrinogen) with the hydrogel by Quartz Crystal Microbalance with Dissipation Monitoring (QCM-D). This technique enables the determination of adsorbant mass and changes in the shear modulus of the hydrogel layer upon adsorption of human proteins. Furthermore, Secondary Ion Mass Spectrometry and principal component analysis was applied to monitor the changed composition of the topmost adsorbate layer. This approach opens interesting perspectives for a sensitive screening of viscoelastic biomaterials that could be used for regenerative medicine. PMID:24956040

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

    PubMed

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

    2016-02-14

    Healthy weight loss represents a real challenge when obesity is increasing in prevalence. Herein, we report a conjugated polymer nanocarrier for smart deactivation of lipase and thus balancing calorie intake. After oral administration, the nanocarrier is sensitive to lipase in the digestive tract and releases orlistat, which deactivates the enzyme and inhibits fat digestion. It also creates negative feedback to control the release of itself. The nanocarrier smartly regulates activity of the lipase cyclically varied between high and low levels. In spite of high fat diet intervention, obese mice receiving a single dose of the nanocarrier lose weight over eight days, whereas a control group continues the tendency to gain weight. Daily intragastric administration of the nanocarrier leads to lower weight of livers or fat pads, smaller adipocyte size, and lower total cholesterol level than that of the control group. Near-infrared fluorescence of the nanocarrier reveals its biodistribution. PMID:26790821

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

    NASA Astrophysics Data System (ADS)

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

    2016-02-01

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

  6. Transformable DNA nanocarriers for plasma membrane targeted delivery of cytokine.

    PubMed

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

    2016-07-01

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

  7. Polymer-based nanocarriers for vaginal drug delivery.

    PubMed

    das Neves, José; Nunes, Rute; Machado, Alexandra; Sarmento, Bruno

    2015-09-15

    The vaginal delivery of various drugs is well described and its relevance established in current medical practice. Alongside recent advances and achievements in the fields of pharmaceutical nanotechnology and nanomedicine, there is an increasing interest in the potential use of different nanocarriers for the delivery of old and new pharmacologically active molecules with either therapeutic or prophylactic purposes. Nanosystems of polymeric nature in particular have been investigated over the last years and their interactions with mucosal fluids and tissues, as well as genital tract biodistribution upon vaginal administration, are now better understood. While different applications have been envisioned, most of the current research is focusing in the development of nano-formulations with the potential to inhibit the vaginal transmission of HIV upon sexual intercourse. The present work focuses its discussion on the potential and perils of polymer-based nanocarriers for the vaginal administration of different pharmacologically active molecules. PMID:25550217

  8. Active Targeted Drug Delivery for Microbes Using Nano-Carriers

    PubMed Central

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

    2015-01-01

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

  9. Recent Trends in Multifunctional Liposomal Nanocarriers for Enhanced Tumor Targeting

    PubMed Central

    Perche, Federico; Torchilin, Vladimir P.

    2013-01-01

    Liposomes are delivery systems that have been used to formulate a vast variety of therapeutic and imaging agents for the past several decades. They have significant advantages over their free forms in terms of pharmacokinetics, sensitivity for cancer diagnosis and therapeutic efficacy. The multifactorial nature of cancer and the complex physiology of the tumor microenvironment require the development of multifunctional nanocarriers. Multifunctional liposomal nanocarriers should combine long blood circulation to improve pharmacokinetics of the loaded agent and selective distribution to the tumor lesion relative to healthy tissues, remote-controlled or tumor stimuli-sensitive extravasation from blood at the tumor's vicinity, internalization motifs to move from tumor bounds and/or tumor intercellular space to the cytoplasm of cancer cells for effective tumor cell killing. This review will focus on current strategies used for cancer detection and therapy using liposomes with special attention to combination therapies. PMID:23533772

  10. Nanocarriers and nanoparticles for skin care and dermatological treatments

    PubMed Central

    Gupta, Sanjeev; Bansal, Radhika; Gupta, Sunita; Jindal, Nidhi; Jindal, Abhinav

    2013-01-01

    Nanotechnology (nano: One billionth) is a novel arena with promising applications in the field of medicine, especially pharmaceuticals for safe and targeted drug delivery. The skin is a phenomenal tool for investigation of nanocarriers for drug delivery for topical and dermatological application. The physicochemical characteristics of the nanoparticles, such as rigidity, hydrophobicity, size and charge are crucial to the skin permeation mechanism. Many nanocarriers such as polymeric, inorganic and lipid nanoparticles and nanoemulsions have been developed and some like carbon nanotubes and fullerenes still need further exploration for future use in skin care and dermatological treatments. Risks of nanopollution and cytotoxicity also need to be kept in mind while exploring various nanoparticles for medical use. PMID:24350003

  11. Photochemical mechanisms of light-triggered release from nanocarriers

    PubMed Central

    Fomina, Nadezda; Sankaranarayanan, Jagadis; Almutairi, Adah

    2012-01-01

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

  12. Pharmaceutical and biomedical applications of lipid-based nanocarriers.

    PubMed

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

    2014-03-01

    Increasing attention is being given to lipid nanocarriers (LNs) as drug delivery systems, due to the advantages offered of a higher biocompatibility and lower toxicity compared with polymeric nanoparticles. Many administration routes are being investigated for LNs, including topical, oral and parenteral ones. LNs are also proposed for specific applications such as cancer treatment, gene therapy, diagnosis and medical devices production. However, the high number of published research articles does not match an equal amount of patents. A recent Review of ours, published in Pharmaceutical Patent Analyst, reported the patents proposing novel methods for the production of LNs. This review work discusses recent patents, filed in 2007-2013 and dealing with the industrial applications of lipid-based nanocarriers for the vectorization of therapeutically relevant molecules, as well as biotech products such as proteins, gene material and vaccines, in the pharmaceutical, diagnostic and biomedical areas. PMID:24588596

  13. Exosomes as nanocarriers for immunotherapy of cancer and inflammatory diseases.

    PubMed

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

    2015-09-01

    Cell secreted exosomes (30-100nm vesicles) play a major role in intercellular communication due to their ability to transfer proteins and nucleic acids from one cell to another. Depending on the originating cell type and the cargo, exosomes can have immunosuppressive or immunostimulatory effects, which have potential application as immunotherapies for cancer and autoimmune diseases. Cellular components shed from tumor cells or antigen presenting cells (APCs), such as dendritic cells, macrophages and B cells, have been shown to be efficiently packaged in exosomes. In this review, we focus on the application of exosomes as nanocarriers and immunological agents for cancer and autoimmune immunotherapy. APC-derived exosomes demonstrate effective therapeutic efficacy for the treatment of cancer and experimental autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis. In addition to their intrinsic immunomodulating activity, exosomes have many advantages over conventional nanocarriers for drug and gene delivery. PMID:25842185

  14. Phage display-guided nanocarrier targeting to atheroprone vasculature

    PubMed Central

    Hofmeister, Lucas H.; Lee, Sue H.; Norlander, Allison E.; Montaniel, Kim Ramil C.; Chen, Wei; Harrison, David G.; Sung, Hak-Joon

    2015-01-01

    In regions of the circulation where vessels are straight and unbranched, blood flow is laminar and unidirectional. In contrast, at sites of curvature, branch points and regions distal to stenoses blood flow becomes disturbed. Atherosclerosis preferentially develops in these regions of disturbed blood flow. Current therapies for atherosclerosis are systemic, and may not sufficiently target these atheroprone regions. In this study, we sought to leverage the alterations on the luminal surface of endothelial cells caused by this atheroprone flow for nanocarrier targeting. In vivo phage display was used to discover unique peptides that selectively bind to atheroprone regions in the mouse partial carotid artery ligation model. The peptide GSPREYTSYMPH (PREY) was found to bind 4.5-fold more avidly to the region of disturbed flow, and was used to form targeted liposomes. When administered intravenously, PREY-targeted liposomes preferentially accumulated in endothelial cells in the partially occluded carotid artery and other areas of disturbed flow. Proteomic analysis and immunoblotting indicated that fibronectin and Filamin A were preferentially bound by PREY-nanocarriers in vessels with disturbed flow. In additional experiments, PREY-nanocarriers were used therapeutically to deliver the nitric oxide synthase co-factor tetrahydrobiopterin (BH4), which we have previously shown to be deficient in regions of disturbed flow. This intervention increased vascular BH4 and reduced vascular superoxide in the partially ligated artery in wild-type mice, and reduced plaque burden in the partially ligated left carotid artery of fat fed atheroprone mice (ApoE−/−). Targeting atheroprone sites of the circulation with functionalized nanocarriers provides a new approach for prevention of early atherosclerotic lesion formation. PMID:25768046

  15. Nanocarriers Based Anticancer Drugs: Current Scenario and Future Perceptions.

    PubMed

    Raj, Rakesh; Mongia, Pooja; Kumar Sahu, Suresh; Ram, Alpana

    2016-01-01

    Anticancer therapies mostly depend on the ability of the bioactives to reach their designated cellular and subcellular target sites, while minimizing accumulation and side effects at non specific sites. The development of nanotechnology based drug delivery systems that are able to modify the biodistribution, tissue uptake and pharmacokinetics of therapeutic agents is considered of great importance in biomedical research and treatment therapy. Controlled releases from nanocarriers can significantly enhance the therapeutic effect of a drug. Nanotechnology has the potential to revolutionize in cancer diagnosis and therapy. Targeted nano medicines either marketed or under development, are designed for the treatment of various types of cancer. Nanocarriers are able to reduce cytotoxic effect of the active anticancer drugs by increasing cancer cell targeting in comparison to conventional formulations. The newly developed nano devices such as quantum dots, liposomes, nanotubes, nanoparticles, micelles, gold nanoparticles, carbon nanotubes and solid lipid nanoparticles are the most promising applications for various cancer treatments. This review is focused on currently available information regarding pharmaceutical nanocarriers for cancer therapy and imaging. PMID:26201484

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

    NASA Astrophysics Data System (ADS)

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

    2007-09-01

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

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

    PubMed Central

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

    2013-01-01

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

  18. Nanocarriers and the delivered drug: effect interference due to intravenous administration.

    PubMed

    Vlasova, Maria A; Rytkönen, Jussi; Riikonen, Joakim; Tarasova, Olga S; Mönkäre, Juha; Kovalainen, Miia; Närvänen, Ale; Salonen, Jarno; Herzig, Karl-Heinz; Lehto, Vesa-Pekka; Järvinen, Kristiina

    2014-10-15

    Intravenously administered nanocarriers are widely studied to improve the delivery of various therapeutic agents. However, recent in vivo studies have demonstrated that intravenously administered nanocarriers that do not contain any drug may affect cardiovascular function. Here we provide an example where the drug and the nanocarrier both affect the same cardiovascular parameters following intravenous administration. The peptide ghrelin antagonist (GhA) increases arterial pressure, while thermally hydrocarbonized porous silicon nanoparticles (THCPSi) transiently decrease it, as assessed with radiotelemetry in conscious rats. As a result, intravenous administration of GhA-loaded THCPSi nanoparticles partially antagonized GhA activity: arterial pressure was not increased. When the cardiovascular effects of GhA were blocked with atenolol pretreatment, GhA-loaded nanoparticles reduced arterial pressure to similar extent as drug-free nanoparticles. These data indicate that the biological activity of a drug delivered within a nanocarrier may be obscured by the biological responses induced by the nanocarrier itself. PMID:24964293

  19. A composite hydrogel system containing glucose-responsive nanocarriers for oral delivery of insulin.

    PubMed

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

    2016-12-01

    Development of an oral delivery strategy for insulin therapeutics has drawn much attention in recent years. In this study, a glucose-responsive nanocarriers for loading of insulin has been prepared firstly. The resultant nanocarriers exhibited relative low cytotoxicity against Caco-2 cells and excellent stability against protein solution. The insulin release behaviors were evaluated triggered by pH and glucose in vitro. In order to enhance the oral bioavailability of insulin, the insulin-loaded glucose-responsive nanocarriers were further encapsulated into a three-dimensional (3D) hyaluronic acid (HA) hydrogel environment for overcoming multiple barriers and providing multi-protection for insulin during the transport process. The hypoglycemic effect for oral delivery of insulin was studied in vivo. After oral administration to the diabetic rats, the released insulin from hydrogel systems containing insulin-loaded glucose-responsive nanocarriers exhibited an effective hypoglycemic effect for longer time compared with insulin-loaded nanocarriers. PMID:27612686

  20. Antibacterial nanocarriers of resveratrol with gold and silver nanoparticles.

    PubMed

    Park, Sohyun; Cha, Song-Hyun; Cho, Inyoung; Park, Soomin; Park, Yohan; Cho, Seonho; Park, Youmie

    2016-01-01

    This study focused on the preparation of resveratrol nanocarrier systems and the evaluation of their in vitro antibacterial activities. Gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs) for resveratrol nanocarrier systems were synthesized using green synthetic routes. During the synthesis steps, resveratrol was utilized as a reducing agent to chemically reduce gold and silver ions to AuNPs and AgNPs. This system provides green and eco-friendly synthesis routes that do not involve additional chemical reducing agents. Resveratrol nanocarriers with AuNPs (Res-AuNPs) and AgNPs (Res-AgNPs) were observed to be spherical and to exhibit characteristic surface plasmon resonance at 547 nm and at 412-417 nm, respectively. The mean size of the nanoparticles ranged from 8.32 to 21.84 nm, as determined by high-resolution transmission electron microscopy. The face-centered cubic structure of the Res-AuNPs was confirmed by high-resolution X-ray diffraction. Fourier-transform infrared spectra indicated that the hydroxyl groups and C=C in the aromatic ring of resveratrol were involved in the reduction reaction. Res-AuNPs retained excellent colloidal stability during ultracentrifugation and re-dispersion, suggesting that resveratrol also played a role as a capping agent. Zeta potentials of Res-AuNPs and Res-AgNPs were in the range of -20.58 to -48.54 mV. Generally, against Gram-positive and Gram-negative bacteria, the Res-AuNPs and Res-AgNPs exhibited greater antibacterial activity compared to that of resveratrol alone. Among the tested strains, the highest antibacterial activity of the Res-AuNPs was observed against Streptococcus pneumoniae. The addition of sodium dodecyl sulfate during the synthesis of Res-AgNPs slightly increased their antibacterial activity. These results suggest that the newly developed resveratrol nanocarrier systems with metallic nanoparticles show potential for application as nano-antibacterial agents with enhanced activities. PMID:26478416

  1. Journey to the Center of the Cell: Current Nanocarrier Design Strategies Targeting Biopharmaceuticals to the Cytoplasm and Nucleus.

    PubMed

    Munsell, Erik V; Ross, Nikki L; Sullivan, Millicent O

    2016-01-01

    New biopharmaceutical molecules, potentially able to provide more personalized and effective treatments, are being identified through the advent of advanced synthetic biology strategies, sophisticated chemical synthesis approaches, and new analytical methods to assess biological potency. However, translation of many of these structures has been significantly limited due to the need for more efficient strategies to deliver macromolecular therapeutics to desirable intracellular sites of action. Engineered nanocarriers that encapsulate peptides, proteins, or nucleic acids are generally internalized into target cells via one of several endocytic pathways. These nanostructures, entrapped within endosomes, must navigate the intracellular milieu to orchestrate delivery to the intended destination, typically the cytoplasm or nucleus. For therapeutics active in the cytoplasm, endosomal escape continues to represent a limiting step to effective treatment, since a majority of nanocarriers trapped within endosomes are ultimately marked for enzymatic degradation in lysosomes. Therapeutics active in the nucleus have the added challenges of reaching and penetrating the nuclear envelope, and nuclear delivery remains a preeminent challenge preventing clinical translation of gene therapy applications. Herein, we review cutting-edge peptide- and polymer-based design strategies with the potential to enable significant improvements in biopharmaceutical efficacy through improved intracellular targeting. These strategies often mimic the activities of pathogens, which have developed innate and highly effective mechanisms to penetrate plasma membranes and enter the nucleus of host cells. Understanding these mechanisms has enabled advances in synthetic peptide and polymer design that may ultimately improve intracellular trafficking and bioavailability, leading to increased access to new classes of biotherapeutics. PMID:26675220

  2. Synthesis of thermosensitive magnetic nanocarrier for controlled sorafenib delivery.

    PubMed

    Heidarinasab, Amir; Ahmad Panahi, Homayon; Faramarzi, Mehdi; Farjadian, Fatemeh

    2016-10-01

    Allyl glycidyl ether/N-isopropylacrylamide-grafted magnetic nanoparticles were prepared using silica-coated magnetic nanoparticles as a substrate for radical copolymerization of allyl glycidyl ether and N-isopropylacrylamide. Chitosan was coupled with the prepared nanoparticles by opening the epoxy ring of the allyl glycidyl ether. The thermosensitive magnetic nanocarrier (TSMNC) obtained can be applied as a potent drug carrier. The TSMNC structure was characterized using Fourier transform infrared spectroscopy, X-ray diffraction, thermogravimetric analysis, differential scanning calorimetry, vibrating sample magnetometer, and elemental analysis. Its morphology and size were investigated using field emission scanning electron microscopy, transmission electron microscopy and dynamic light scattering. The feasibility of employing the TSMNC for adsorption and in vitro controlled release of the chemotherapeutic agent sorafenib was tested. The effect of the adsorption parameters of pH, temperature, and loading time of sorafenib onto TSMNC was evaluated. The adsorption data was fitted to the Langmuir and Freundlich isotherms and the relevant parameters derived. The drug release profile indicated that 88% of the adsorbed drug was released within 35h at 45°C and drug release was Fickian diffusion-controlled. The results confirmed that the TSMNC has a high adsorption capacity at low temperature and good controlled release in a slow rate at a high temperature and could be developed for further application as a drug nanocarrier. PMID:27287097

  3. Methocel-Lipid Hybrid Nanocarrier for Efficient Oral Insulin Delivery.

    PubMed

    Boushra, Mariam; Tous, Sozan; Fetih, Gihan; Xue, Hui-Yi; Tran, Ngoc T; Wong, Ho Lun

    2016-05-01

    Even with the use of double-emulsion technique for preparation, the hydrophobic nature of solid lipid nanoparticles (SLNs) limits their encapsulation efficiency (EE%) for peptides such as insulin. In this study, we hypothesize that inclusion of Methocel into SLN to form Methocel-lipid hybrid nanocarriers (MLNs) will significantly enhance insulin EE% without compromising the various characteristics of SLN favorable for oral drug delivery. Our data show that incorporation of 2% wt/wt of Methocel A15C had doubled insulin EE% (around 40%) versus conventional SLN prepared using standard double emulsion technique. MLN significantly protected the entrapped insulin against chymotrypsin degradation at gastrointestinal pH. Using intestinal epithelial cells Caco2 as a model, it was shown that MLN could be extensively taken up by Caco2 cells while demonstrating low cytotoxicity. The results indicate that MLN have preserved the key advantages of SLN (biocompatibility, low cytotoxicity, good drug protection, and good interaction with cells) while overcoming their key limitation for efficient peptide entrapment. Based on this, MLN may serve as a promising nanocarrier for oral delivery of peptides. PMID:27012226

  4. Formulation and nebulization of fluticasone propionate-loaded lipid nanocarriers.

    PubMed

    Umerska, Anita; Mouzouvi, Celia R A; Bigot, André; Saulnier, Patrick

    2015-09-30

    Inhaled fluticasone propionate (FP) is often prescribed as a first-line therapy for the effective management of pulmonary diseases such as asthma. As nanocarriers offer many advantages over other drug delivery systems, this study investigated the suitability of lipid nanocapsules (LNCs) as a carrier for fluticasone propionate, examining the drug-related factors that should be considered in the formulation design and the behaviour of LNCs with different compositions and properties suspended within aerosol droplets under the relatively hostile conditions of nebulization. By adjusting the formulation conditions, particularly the nanocarrier composition, FP was efficiently encapsulated within the LNCs with a yield of up to 97%, and a concentration comparable to commercially available preparations was achieved. Moreover, testing the solubility of the drug in oil and water and determining the oil/water partition coefficient proved to be useful when assessing the encapsulation of the FP in the LNC formulation. Nebulization did not cause the FP to leak from the formulation, and no phase separation was observed after nebulization. LNCs with a diameter of 100 nm containing a smaller amount of surfactant and a larger amount of oil provided a better FP-loading capacity and better stability during nebulization than 30 or 60 nm LNCs. PMID:26183331

  5. Nanocarrier-based immunotherapy in cancer management and research

    PubMed Central

    Singh, Manu Smriti; Bhaskar, Sangeeta

    2014-01-01

    Research in cancer immunotherapy has gained momentum in the last two decades, with many studies and clinical trials showing positive therapeutic outcomes. Immunotherapy can elicit not only a strong anticancer immune response which could even control metastases, but could also induce immunological memory, resulting in long-lasting protection in the prophylactic setting and protection against possible recurrence. Nanocarriers offer an attractive means for delivery of a multitude of therapeutic immunomodulators which are readily taken up by immune cells and can initiate a particular arm of an immunostimulatory cascade leading to tumor cell killing. This review focuses on recent advances in nanocarrier-mediated immunotherapy for the treatment of cancer. Both in vitro and in vivo studies as well as clinical progress are discussed in various sections. Description of the specific role of nanoparticle technology in immunotherapy highlights the way particles can be tailor-made in terms of size, structure, payload, and surface properties for active targeting to antigen-presenting cells and/or enhanced accumulation in the solid tumor. PMID:27471704

  6. Dual targeted nanocarrier for brain ischemic stroke treatment.

    PubMed

    Zhao, Yue; Jiang, Yan; Lv, Wei; Wang, Zhongyuan; Lv, Lingyan; Wang, Baoyan; Liu, Xin; Liu, Yang; Hu, Quanyin; Sun, Wujin; Xu, Qunwei; Xin, Hongliang; Gu, Zhen

    2016-07-10

    Focal cerebral ischemia, known as stroke, causes serious long-term disabilities globally. Effective therapy for cerebral ischemia demands a carrier that can penetrate the blood-brain barrier (BBB) and subsequently target the ischemia area in brain. Here, we designed a novel neuroprotectant (ZL006) loaded dual targeted nanocarrier based on liposome (T7&SHp-P-LPs/ZL006) conjugated with T7 peptide (T7) and stroke homing peptide (SHp) for penetrating BBB and targeting ischemia area, respectively. Compared with non-targeting liposomes, T7&SHp-P-LPs/ZL006 could transport across BCEC cells and significantly enhance cellular uptake and reduce cells apoptosis of excitatory amino acid stimulated PC-12 cells. However, there was no significant difference in cellular uptake between SHp-modified and plain liposomes when PC-12 cells were incubated without excitatory amino acid. Besides, ex vivo fluorescent images indicated that DiR labeled T7&SHp-P-LPs could efficiently transport across BBB and mostly accumulated in ischemic region rather than normal cerebral hemisphere of MCAO rats. Furthermore, T7&SHp-P-LPs/ZL006 could enhance the ability of in vivo anti-ischemic stroke of MCAO rats. These results demonstrated that T7&SHp-P-LPs could be used as a safe and effective dual targeted nanocarrier for ischemic stroke treatment. PMID:27142584

  7. Recent advances in multifunctional silica-based hybrid nanocarriers for bioimaging and cancer therapy.

    PubMed

    Lim, Wei Qi; Phua, Soo Zeng Fiona; Xu, Hesheng Victor; Sreejith, Sivaramapanicker; Zhao, Yanli

    2016-07-01

    In recent years, there has been a considerable research focus on integrating cancer cell imaging and therapeutic functions into single nanoscale platforms for better treatment of cancer. This task could often be achieved by incorporating multiple components into a hybrid nanosystem. In this minireview, we highlight different types of silica-based hybrid nanosystems and their recent applications as integrated multifunctional platforms for cancer imaging and treatment. The discussions are divided into several sections focusing on various types of materials employed to integrate with silica, which include silica-metallic nanoparticle based hybrid nanocarriers, silica-gold nanoparticle based hybrid nanocarriers, silica-quantum dot based hybrid nanocarriers, silica-upconversion nanoparticle based hybrid nanocarriers, silica-carbon based hybrid nanocarriers, and organosilica nanocarriers. Therapeutic agents loaded in such hybrids include chemodrugs, proteins, DNA/RNA and photosensitizers. For targeted delivery into tumor sites, targeting ligands such as antibodies, peptides, aptamers, and other small molecules are grafted on the surface of the nanocarriers. At the end of the review, a brief summary and research outlook are presented. This minireview aims to provide a quick update of recent research achievements in the field. PMID:26750573

  8. Extracellularly activated nanocarriers: A new paradigm of tumor targeted drug delivery

    PubMed Central

    Gullotti, Emily; Yeo, Yoon

    2009-01-01

    One of the main goals of nanomedicine is to develop a nanocarrier that can selectively deliver anti-cancer drugs to the targeted tumors. Extensive efforts have resulted in several tumor-targeted nanocarriers, some of which are approved for clinical use. Most nanocarriers achieve tumor-selective accumulation through the enhanced permeability and retention effect. Targeting molecules such as antibodies, peptides, ligands, or nucleic acids attached to the nanocarriers further enhance their recognition and internalization by the target tissues. While both the stealth and targeting features are important for effective and selective drug delivery to the tumors, achieving both features simultaneously is often found to be difficult. Some of the recent targeting strategies have the potential to overcome this challenge. These strategies utilize the unique extracellular environment of tumors to change the long-circulating nanocarriers to release the drug or interact with cells in a tumor-specific manner. This review discusses the new targeting strategies with recent examples, which utilize the environmental stimuli to activate the nanocarriers. Traditional strategies for tumor-targeted nanocarriers are briefly discussed with an emphasis on their achievements and challenges. PMID:19366234

  9. Recent advances in multifunctional silica-based hybrid nanocarriers for bioimaging and cancer therapy

    NASA Astrophysics Data System (ADS)

    Lim, Wei Qi; Phua, Soo Zeng Fiona; Xu, Hesheng Victor; Sreejith, Sivaramapanicker; Zhao, Yanli

    2016-06-01

    In recent years, there has been a considerable research focus on integrating cancer cell imaging and therapeutic functions into single nanoscale platforms for better treatment of cancer. This task could often be achieved by incorporating multiple components into a hybrid nanosystem. In this minireview, we highlight different types of silica-based hybrid nanosystems and their recent applications as integrated multifunctional platforms for cancer imaging and treatment. The discussions are divided into several sections focusing on various types of materials employed to integrate with silica, which include silica-metallic nanoparticle based hybrid nanocarriers, silica-gold nanoparticle based hybrid nanocarriers, silica-quantum dot based hybrid nanocarriers, silica-upconversion nanoparticle based hybrid nanocarriers, silica-carbon based hybrid nanocarriers, and organosilica nanocarriers. Therapeutic agents loaded in such hybrids include chemodrugs, proteins, DNA/RNA and photosensitizers. For targeted delivery into tumor sites, targeting ligands such as antibodies, peptides, aptamers, and other small molecules are grafted on the surface of the nanocarriers. At the end of the review, a brief summary and research outlook are presented. This minireview aims to provide a quick update of recent research achievements in the field.

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

    PubMed Central

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

    2015-01-01

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

  11. Hydrodynamic interactions for complex-shaped nanocarriers in targeted drug delivery

    NASA Astrophysics Data System (ADS)

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

    2014-11-01

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

  12. Investigation of strategies for drug delivery by combination targeting of nanocarriers to multiple epitopes or receptors

    NASA Astrophysics Data System (ADS)

    Papademetriou, Iason Titos

    Development of drug delivery systems (ie. nanocarriers) with controllable composition, architecture, and functionalities is heavily investigated in the field of drug delivery in order to improve clinical interventions. Designing drug nanocarriers which possess targeting properties is critical to enable them to reach the intended site of intervention in the body. To achieve this goal, the surface of drug nanocarriers can be modified with targeting moieties (antibodies, peptides, etc.) addressed to cell surface molecules expressed on the diseased tissues and cells. If these molecules are receptors capable of internalizing bound ligands via endocytosis, targeting can then enable drug transport into cells or across cellular barriers in the body. Yet, addressing nanocarriers to single targets presents limited control over cellular interactions and biodistribution. Since most cell-surface markers are not exclusively expressed in a precise site in vivo, high affinity of targeted nanocarriers may lead to non-desired accumulation in regions of the body associated with low expression. Modification of nanocarriers to achieve combined-targeting (binding to more than one cell-surface receptor) may help modulate binding to cells and also endocytosis, since cell receptors possess distinct functions and features affecting these parameters, such as their expression, location on the plasmalemma, activation in disease, mechanism of endocytosis, etc. Further, targeting nanocarriers to multiple epitopes of the same receptor, a strategy which has never been tested, may also modulate these parameters since they are highly epitope specific. In this dissertation, we investigate the effect of targeting model polymer nanocarriers to: (1) multiple receptors of similar function (intercellular-, platelet-endothelial-, and/or vascular-cell adhesion molecules), (2) multiple receptors of different function (intercellular adhesion molecule 1 and transferrin receptor), or (3) multiple epitopes of

  13. Lipid-based nanocarriers for breast cancer treatment - comprehensive review.

    PubMed

    Talluri, Siddartha Venkata; Kuppusamy, Gowthamarajan; Karri, Veera Venkata Satyanarayana Reddy; Tummala, Shashank; Madhunapantula, SubbaRao V

    2016-05-01

    Breast cancer is the second leading cancer-related disease as the most common non-cutaneous malignancy among women. Curative options for breast cancer are limited, therapeutically substantial and associated with toxicities. Emerging nanotechnologies exhibited the possibility to treat or target breast cancer. Among the nanoparticles, various lipid nanoparticles namely, liposomes, solid lipid nanoparticles, nanostructured lipid carriers and lipid polymer hybrid nanoparticles have been developed over the years for the breast cancer therapy and evidences are documented. Concepts are confined in lab scale, which needs to be transferred to large scale to develop active targeting nanomedicine for the clinical utility. So, the present review highlights the recently published studies in the development of lipid-based nanocarriers for breast cancer treatment. PMID:26430913

  14. Spherical and tubule nanocarriers for sustained drug release

    PubMed Central

    Shutava, T.; Fakhrullin, R.; Lvov, Y.

    2014-01-01

    We discuss new trends in Layer-by-Layer (LbL) encapsulation of spherical and tubular cores of 50–150 nm diameter and loaded with drugs. This core size decrease (from few micrometers to a hundred of nanometers) for LbL encapsulation required development of sonication assistant non-washing technique and shell PEGylation to reach high colloidal stability of drug nanocarriers at 2–3 mg/mL concentration in isotonic buffers and serum. For 120–170 nm spherical LbL nanocapsules of low soluble anticancer drugs, polyelectrolyte shell thickness controls drug dissolution. As for nanotube carriers, we concentrated on natural halloysite clay nanotubes as cores for LbL encapsulation that allows high drug loading and sustains its release over tens and hundreds hours. Further drug release prolongation was reached with formation of the tube-end stoppers. PMID:25450068

  15. Review: Milk Proteins as Nanocarrier Systems for Hydrophobic Nutraceuticals.

    PubMed

    Kimpel, Florian; Schmitt, Joachim J

    2015-11-01

    Milk proteins and milk protein aggregates are among the most important nanovehicles in food technology. Milk proteins have various functional properties that facilitate their ability to carry hydrophobic nutraceutical substances. The main functional transport properties that were examined in the reviewed studies are binding of molecules or ions, surface activity, aggregation, gelation, and interaction with other polymers. Hydrophobic binding has been investigated using caseins and isolated β-casein as well as whey proteins. Surface activity of caseins has been used to create emulsion-based carrier systems. Furthermore, caseins are able to self-assemble into micelles, which can incorporate molecules. Gelation and interaction with other polymers can be used to encapsulate molecules into protein networks. The release of transported substances mainly depends on pH and swelling behavior of the proteins. The targeted use of nanocarrier systems requires specific knowledge about the binding mechanisms between the proteins and the carried substances in a certain food matrix. PMID:26467442

  16. Bio-inspired cisplatin nanocarriers for osteosarcoma treatment.

    PubMed

    Zhou, Haidong; Wang, Gangxiang; Lu, Yiyun; Pan, Zhijun

    2016-08-19

    In this study, cisplatin (cis-diaminedichloroplatinum, CDDP) nanocarriers with phosphorylcholine surface tailoring were developed to enhance the anti-tumor potential of CDDP for the treatment of osteosarcoma. Poly(2-methacryloyloxyethyl phosphorylcholine)-b-poly(methacrylic acid) (PMPC-b-PMAA) was synthesized for the preparation of CDDP/PMPC-b-PMAA micelles. The synthesis, self-assembly, and in vitro drug release were well characterized. In vitro cytotoxicity showed that CDDP/PMPC-b-PMAA micelles can strongly inhibit the proliferation of Saos-2 cells. In vivo experiments indicated that CDDP/PMPC-b-PMAA micelles showed prolonged circulation time, reduced renal accumulation, and enhanced tumor accumulation compared to free CDDP. Overall, the CDDP/PMPC-b-PMAA micelles exhibited optimal anti-tumor activity with minimal side effects in the treatment of osteosarcoma. PMID:27315174

  17. Light-Activated Hypoxia-Responsive Nanocarriers for Enhanced Anticancer Therapy.

    PubMed

    Qian, Chenggen; Yu, Jicheng; Chen, Yulei; Hu, Quanyin; Xiao, Xuanzhong; Sun, Wujin; Wang, Chao; Feng, Peijian; Shen, Qun-Dong; Gu, Zhen

    2016-05-01

    A light-activated hypoxia-responsive conjugated polymer-based nanocarrier is developed for efficiently producing singlet oxygen ((1) O2 ) and inducing hypoxia to promote release of its cargoes in tumor cells, leading to enhanced antitumor efficacy. This dual-responsive nanocarrier provides an innovative design guideline for enhancing traditional photodynamic therapeutic efficacy integrated with a controlled drug-release modality. PMID:26948067

  18. A 5-fluorouracil-loaded pH-responsive dendrimer nanocarrier for tumor targeting.

    PubMed

    Jin, Yiguang; Ren, Xia; Wang, Wei; Ke, Lijing; Ning, Erjuan; Du, Lina; Bradshaw, Jeremy

    2011-11-28

    A novel long-circulating and pH-responsive dendrimer nanocarrier was prepared for delivering 5-fluorouracil (5-FU) to tumors through the targeting of nanoparticles to the low pH environment of tumors. The nanocarrier, poly(2-(N,N-diethylamino)ethyl methacrylate) with methoxy-poly(ethylene glycol)-poly(amidoamine) (PPD), had a core-shell structure with 4.0 G poly(amidoamine) (PAMAM) as the core and parallel poly(2-(N,N-diethylamino)ethyl methacrylate) (PDEA) chains and methoxy-poly(ethylene glycol) (mPEG) chains as the shell. The PDEA chain was pH-responsive, and the PEG chains led to long circulation in blood vessels to achieve tumor targeting. The sizes, drug encapsulation and release of PPD nanocarriers showed high pH-dependency due to the PDEA chains, as they were hydrophilic at pH 6.5 and hydrophobic at pH 7.4. The encapsulation efficiency of 5-FU in PPD nanocarriers was as high as 92.5% through the pH transition. The release of 5-FU from PPD nanocarriers was much faster at pH 6.5 than at pH 7.4. The 5-FU-loaded nanocarrier had a long half-life after intravenous administration in mice and showed high tumor targeting. This nanocarrier composite also showed enhanced anticancer effects. PPD is a promising nanocarrier of anticancer drugs with high encapsulation, tumor targeting and pH-responsive release in tumors. PMID:21925254

  19. Hypoxia-responsive nanocarriers for cancer imaging and therapy: recent approaches and future perspectives.

    PubMed

    Thambi, Thavasyappan; Park, Jae Hyung; Lee, Doo Sung

    2016-06-30

    Hypoxia, a condition in which the tissue is deprived of adequate oxygen supply, is a salient feature of various intractable diseases, including rheumatoid arthritis, ischemic stroke, and solid tumors. In particular, hypoxic regions in tumors are often associated with invasiveness, metastasis, and resistance to radiotherapy and chemotherapy. Given its unique role in tumor progression, hypoxia has been considered to be a primary target for the diagnosis and treatment of cancer. Owing to their sizes and tailorable physicochemical characteristics, nanocarriers are an emerging class of materials that are increasingly utilized in biomedical applications. Particularly, stimuli-responsive nanocarriers, which release their payloads specifically at the tumor-microenvironment, are materials of interest. Owing to the aberrant vascular properties of tumors, the transportation of anticancer drugs to hypoxic regions is challenging because they are distant from blood vessels. In addition, hypoxia upregulates various genes involved in drug resistance such as P-glycoprotein. To surmount the issues associated with hypoxia, nanocarriers that can release imaging agents or anticancer drugs in hypoxic regions must be developed. This review focuses on recently developed hypoxia-responsive conjugates or nanocarriers and their potential applications in cancer imaging and therapy. Low oxygen levels bring forth conformational changes in hypoxia-responsive nanocarriers through the cleavage or reduction of hypoxia-responsive functional groups. A greater understanding of these changes will help to design more efficient nanocarriers to address the challenges encountered with hypoxia in conventional chemotherapy. PMID:27225824

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

    PubMed

    Zhao, Jing; Feng, Si-Shen

    2015-07-01

    A major problem in cancer treatment is the multidrug resistance. siRNA inhibitors have great advantages to solve the problem, if the bottleneck of their delivery could be well addressed by the various nanocarriers. Moreover, co-delivery of siRNA together with the various anticancer agents in one nanocarrier may maximize their additive or synergistic effect. This review provides a comprehensive summary on the state-of-the-art of the nanocarriers, which may include prodrugs, micelles, liposomes, dendrimers, nanohydrogels, solid lipid nanoparticles, nanoparticles of biodegradable polymers and nucleic acid nanocarriers for delivery of siRNA and co-delivery of siRNA together with anticancer agents with focus on synthesis of the nanocarrier materials, design and characterization, in vitro and in vivo evaluation, and prospect and challenges of nanocarriers. PMID:26214357

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

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

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

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

    PubMed

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

    2016-04-14

    The recent development of bioactive glasses with nanoscale morphologies has spurred their specific applications in bone regeneration, for example as drug and gene delivery carriers. Bone engineering with stem cells genetically modified with this unique class of nanocarriers thus holds great promise in this avenue. Here we report the potential of the bioactive glass nanoparticle (BGN) system for the gene delivery of mesenchymal stem cells (MSCs) targeting bone. The composition of 15% Ca-added silica, proven to be bone-bioactive, was formulated into surface aminated mesoporous nanospheres with enlarged pore sizes, to effectively load and deliver bone morphogenetic protein-2 (BMP2) plasmid DNA. The enlarged mesopores were highly effective in loading BMP2-pDNA with an efficiency as high as 3.5 wt% (pDNA w.r.t. BGN), a level more than twice than for small-sized mesopores. The BGN nanocarriers released the genetic molecules in a highly sustained manner (for as long as 2 weeks). The BMP2-pDNA/BGN complexes were effectively internalized to rat MSCs with a cell uptake level of ∼73%, and the majority of cells were transfected to express the BMP2 protein. Subsequent osteogenesis of the transfected MSCs was demonstrated by the expression of bone-related genes, including bone sialoprotein, osteopontin, and osteocalcin. The MSCs transfected with BMP2-pDNA/BGN were locally delivered inside a collagen gel to the target calvarium defects. The results showed significantly improved bone regeneration, as evidenced by the micro-computed tomographic, histomorphometric and immunohistochemical analyses. This study supports the excellent capacity of the BGN system as a pDNA-delivery nanocarrier in MSCs, and the engineered system, BMP2-pDNA/BGN with MSCs, may be considered a new promising candidate to advance the therapeutic potential of stem cells through genetic modification, targeting bone defects and diseases. PMID:27035682

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-02-01

    Although graphene based drug delivery has gained significant recent interest, the synthesis of colloidal graphene based nanocarriers with high drug loading capacities and with targeting ligands at the outer surface is a challenging issue. We have synthesized carbohydrate coated and folate functionalized colloidal graphene which can be used as a nanocarrier for a wide variety of hydrophobic and hydrophilic drugs. The synthesized colloidal graphene is loaded with paclitaxol, camptothecin, doxorubicin, curcumin and used for their targeted delivery to cancer cells. We demonstrate that this drug loaded functional graphene nanocarrier can successfully deliver drugs into target cells and offers an enhanced therapeutic performance. The reported approach can be extended to the cellular delivery of other hydrophobic and hydrophilic drugs and the simultaneous delivery of multiple drugs.Although graphene based drug delivery has gained significant recent interest, the synthesis of colloidal graphene based nanocarriers with high drug loading capacities and with targeting ligands at the outer surface is a challenging issue. We have synthesized carbohydrate coated and folate functionalized colloidal graphene which can be used as a nanocarrier for a wide variety of hydrophobic and hydrophilic drugs. The synthesized colloidal graphene is loaded with paclitaxol, camptothecin, doxorubicin, curcumin and used for their targeted delivery to cancer cells. We demonstrate that this drug loaded functional graphene nanocarrier can successfully deliver drugs into target cells and offers an enhanced therapeutic performance. The reported approach can be extended to the cellular delivery of other hydrophobic and hydrophilic drugs and the simultaneous delivery of multiple drugs. Electronic supplementary information (ESI) available: Details of the characterisation of carbohydrate functionalisation, images of different drug/dye loaded graphene nanocarriers at 3 hours incubation time, controlled cell

  5. Engineering hybrid exosomes by membrane fusion with liposomes

    PubMed Central

    Sato, Yuko T.; Umezaki, Kaori; Sawada, Shinichi; Mukai, Sada-atsu; Sasaki, Yoshihiro; Harada, Naozumi; Shiku, Hiroshi; Akiyoshi, Kazunari

    2016-01-01

    Exosomes are a valuable biomaterial for the development of novel nanocarriers as functionally advanced drug delivery systems. To control and modify the performance of exosomal nanocarriers, we developed hybrid exosomes by fusing their membranes with liposomes using the freeze–thaw method. Exosomes embedded with a specific membrane protein isolated from genetically modified cells were fused with various liposomes, confirming that membrane engineering methods can be combined with genetic modification techniques. Cellular uptake studies performed using the hybrid exosomes revealed that the interactions between the developed exosomes and cells could be modified by changing the lipid composition or the properties of the exogenous lipids. These results suggest that the membrane-engineering approach reported here offers a new strategy for developing rationally designed exosomes as hybrid nanocarriers for use in advanced drug delivery systems. PMID:26911358

  6. A new drug nanocarrier consisting of polyarginine and hyaluronic acid.

    PubMed

    Oyarzun-Ampuero, Felipe A; Goycoolea, Francisco M; Torres, Dolores; Alonso, Maria J

    2011-09-01

    The purpose of this study was to produce and characterize a variety of nanostructures comprised of the polyaminoacid polyarginine (PArg) and the polysaccharide hyaluronic acid (HA) as a preliminary stage before evaluating their potential application in drug delivery. PArg was combined with high- or low-molecular-weight HA (HMWHA or LMWHA, respectively) to form nanoparticles by simply mixing polymeric aqueous solutions at room temperature. The average size of the resulting nanocarriers was between 116 and 155 nm, and their zeta potential value ranged from +31.3 to -35.9 mV, indicating that the surface composition of the particle could be conveniently modified according to the mass ratio of the polymers. Importantly, the systems prepared with HMWHA remained stable after isolation by centrifugation and in conditions that mimic the physiological medium, whereas particles that incorporated LMWHA were unstable. Transmission electron microscopy showed that the nanostructures made with HMWHA were spherical. Finally, the systems were stable for at least three months at storage conditions (4°C). PMID:21549838

  7. S-layer coated emulsomes as potential nanocarriers.

    PubMed

    Ucisik, Mehmet H; Küpcü, Seta; Debreczeny, Monika; Schuster, Bernhard; Sleytr, Uwe B

    2013-09-01

    The present study introduces a novel nanocarrier system comprising lipidic emulsomes and S-layer (fusion) proteins as functionalizing tools coating the surface. Emulsomes composed of a solid tripalmitin core and a phospholipid shell are created reproducibly with an average diameter of approximately 300 nm using temperature-controlled extrusion steps. Both wildtype (wt) and recombinant (r) S-layer protein SbsB of Geobacillus stearothermophilus PV72/p2 are capable of forming coherent crystalline envelope structures with oblique (p1) lattice symmetry, as evidenced by transmission electron microscopy. Upon coating with wtSbsB, positive charge of emulsomes shifts to a highly negative zeta potential, whereas those coated with rSbsB become charge neutral. This observation is attributed to the presence of a negatively charged glycan, the secondary cell wall polymer (SCWP), which is associated only with wtSbsB. The present study shows for the first time the ability of recombinant and wildtype S-layer proteins to cover the entire surface of emulsomes with its characteristic crystalline lattice. Furthermore, in vitro cell culture studies reveal that S-layer coated emulsomes can be uptaken by human liver carcinoma cells (HepG2) without showing any significant cytotoxicity over a wide range of concentrations. The utilization of S-layer fusion proteins equipped in a nanopatterned fashion by identical or diverse functions may lead to further development of emulsomes in nanomedicine, especially for drug delivery and targeting. PMID:23606662

  8. Lycopene from tomatoes: vesicular nanocarrier formulations for dermal delivery.

    PubMed

    Ascenso, Andreia; Pinho, Sónia; Eleutério, Carla; Praça, Fabíola Garcia; Bentley, Maria Vitória Lopes Badra; Oliveira, Helena; Santos, Conceição; Silva, Olga; Simões, Sandra

    2013-07-31

    This experimental work aimed to develop a simple, fast, economic, and environmentally friendly process for the extraction of lycopene from tomato and incorporate this lycopene-rich extract into ultradeformable vesicular nanocarriers suitable for topical application. Lycopene extraction was conducted without a cosolvent for 30 min. The extracts were analyzed and incorporated in transfersomes and ethosomes. These formulations were characterized, and the cellular uptake was observed by confocal microscopy. Dermal delivery of lycopene formulations was tested under in vitro and in vivo conditions. Lycopene extraction proved to be quite safe and selective. The vesicular formulation was taken up by the cells, being more concentrated around the nucleus. Epicutaneous application of lycopene formulations decreased the level of anthralin-induced ear swelling by 97 and 87%, in a manner nonstatistically different from the positive control. These results support the idea that the lycopene-rich extract may be a good alternative to the expensive commercial lycopene for incorporation into advanced topical delivery systems. PMID:23826819

  9. A highlight on lipid based nanocarriers for transcutaneous immunization.

    PubMed

    Nasr, Maha; Abdel-Hamid, Sameh; Alyoussef, Abdullah A

    2015-01-01

    Transcutaneous vaccination has become a widely used technique for providing immunity against several types of pathogens, taking advantage of the immune components found in the skin. The success in the field of vaccination has not only relied on the type of antigen and adjuvant delivered, but also on how they are delivered. In this regard, particulate carriers, especially nanoparticles have evoked considerable interest, owing to the desirable properties that they impart to the substance being delivered. The presentation of antigens by the nanoparticles mimics the presentation of the immunogen by the pathogen; hence, it creates a similar immune response. Furthermore, nanoparticles protect the antigen from degradation and allow its prolonged release, which maximizes its exposure to the immune cells. The most commonly used materials for the formulation of nanoparticles are either polymer-based or lipid based. This review will focus on the lipid based nanocarriers, either vesicular such as liposomes, transfersomes, and ethosomes, or non-vesicular such as cubosomes, solid lipid nanoparticles, nano-structured lipid carriers, solid in oil nanodispersions, lipoplexes, and hybrid polymeric-lipidic systems. The applications of these carriers in the field of transcutaneous immunization will be discussed in this review as well. PMID:25658381

  10. Potentials of new nanocarriers for dermal and transdermal drug delivery.

    PubMed

    Neubert, Reinhard H H

    2011-01-01

    Nanocarriers (NCs) are colloidal systems having structures below a particle or droplet size of 500 nm. In the previous years, the focus for the application of NCs was primarily placed on the parenteral and oral application. However, NCs applied to the skin are in the center of attention and are expected to be increasingly applied as the skin offers a lot of advantages for the administration of such systems. For the use of NCs to the skin, one has to differentiate between the desired effects: the local effect within the skin (dermal drug delivery) or a systemic effect accompanied by the permeation through the skin (transdermal drug delivery). Both for dermal and transdermal drug delivery, the stratum corneum (SC), the main barrier of the skin, has to be overcome. SC is one of the tightest barriers of the human body. Therefore, it is the primary goal of new NC to overcome this protective and effective barrier. For that purpose, new NCs such as microemulsions, vesicular (liposomes) and nanoparticular NCs are developed and investigated. This article evaluates the potentials of these NCs for dermal and transdermal drug delivery. PMID:21111043

  11. Determining drug release rates of hydrophobic compounds from nanocarriers.

    PubMed

    D'Addio, Suzanne M; Bukari, Abdallah A; Dawoud, Mohammed; Bunjes, Heike; Rinaldi, Carlos; Prud'homme, Robert K

    2016-07-28

    Obtaining meaningful drug release profiles for drug formulations is essential prior to in vivo testing and for ensuring consistent quality. The release kinetics of hydrophobic drugs from nanocarriers (NCs) are not well understood because the standard protocols for maintaining sink conditions and sampling are not valid owing to mass transfer and solubility limitations. In this work, a new in vitroassay protocol based on 'lipid sinks' and magnetic separation produces release conditions that mimic the concentrations of lipid membranes and lipoproteins in vivo, facilitates separation, and thus allows determination of intrinsic release rates of drugs from NCs. The assay protocol is validated by (i) determining the magnetic separation efficiency, (ii) demonstrating that sink condition requirements are met, and (iii) accounting for drug by completing a mass balance. NCs of itraconazole and cyclosporine A (CsA) were prepared and the drug release profiles were determined. This release protocol has been used to compare the drug release from a polymer stabilized NC of CsA to a solid drug NP of CsA alone. These data have led to the finding that stabilizing block copolymer layers have a retarding effect on drug release from NCs, reducing the rate of CsA release fourfold compared with the nanoparticle without a polymer coating.This article is part of the themed issue 'Soft interfacial materials: from fundamentals to formulation'. PMID:27298440

  12. Radiolabeled D-Penicillamine Magnetic Nanocarriers for Targeted Purposes.

    PubMed

    Özyüncü, Seniha Yolcular; Teksöz, Serap; Içhedef, Çiğdem; Medinel, E Ilker; Avci, Çiğir Biray; Gündüz, Cumhur; Ünak, Perihan

    2016-04-01

    The aim of this study is to synthesize D-Penicillamine (D-PA) conjugated magnetic nanocarriers for targeted purposes. Magnetic nanoparticles were prepared by partial reduction method and surface modification was done with an amino silane coupling agent's (structural properties), AEAPS, the particles were characterized by Scanning Electron Microscope (SEM), X-ray Diffraction (XRD). After that D-PA was linked with the magnetic nanoparticles (MNPs) and has been radiolabeled with [99mTc(CO)3]+ core. Quality controls of [99mTc(CO)3-MNP-D-PA] were established by Cd(Te) detector. The radiolabeling efficiency of magnetic nanoparticles ([99mTc(CO)3-MNP-D-PA]) was about 97.05% with good in vitro stability during the 24 hour period. As a parallel study, radiolabeled D-PA complex ([99mTc(CO)3-D-PA]) was prepared with a radiolabeling yield of 97.93%. At the end, biologic activities of binding complexes were investigated on MCF7 human breast cancer cells. Our results show that, radiolabeled magnetic nanoparticles with core [99mTc(CO)3]+ ([99mTc(CO)3-MNP-D-PA]) showed the highest uptake on MCF7 cells which were applied magnetic field in the wells. In that case, result of this study emphasizes that radiolabeled magnetic nanoparticles with core [99mTc(CO)3]+ would support new occurrences of new agents. PMID:27451783

  13. DNA/Fusogenic Lipid Nanocarrier Assembly: Millisecond Structural Dynamics.

    PubMed

    Angelov, Borislav; Angelova, Angelina; Filippov, Sergey K; Narayanan, Theyencheri; Drechsler, Markus; Štěpánek, Petr; Couvreur, Patrick; Lesieur, Sylviane

    2013-06-01

    Structural changes occurring on a millisecond time scale during uptake of DNA by cationic lipid nanocarriers are monitored by time-resolved small-angle X-ray scattering (SAXS) coupled to a rapid-mixing stopped-flow technique. Nanoparticles (NPs) of nanochannel organization are formed by PEGylation, hydration, and dispersion of a lipid film of the fusogenic lipid monoolein in a mixture with positively charged (DOMA) and PEGylated (DOPE-PEG2000) amphiphiles and are characterized by the inner cubic structure of very large nanochannels favorable for DNA upload. Ultrafast structural dynamics of complexation and assembly of these cubosome particles with neurotrophic plasmid DNA (pDNA) is revealed thanks to the high brightness of the employed synchrotron X-ray beam. The rate constant of the pDNA/lipid NP complexation is estimated from dynamic roentgenograms recorded at 4 ms time resolution. pDNA upload into the vastly hydrated channels of the cubosome carriers leads to a fast nanoparticle-nanoparticle structural transition and lipoplex formation involving tightly packed pDNA. PMID:26283134

  14. Kinetic and Thermodynamic Stability of Organic and Inorganic Nanocarriers

    NASA Astrophysics Data System (ADS)

    Yefimova, S. L.; Tkacheva, T. N.; Klochkov, V. K.; Sorokin, A. V.; Malyukin, Yu. V.

    2015-05-01

    The kinetic and thermodynamic stability of organic (sodium dodecylsulfate micelles and egg-yolk phosphatidylcholine zwitterionic liposomes) and inorganic (based on GdYVO0034:Eu3+ nanoparticles) nanocarriers (NCs) was studied by the λ-ratiometric method (analysis of fluorescence intensity at two wavelengths) using non-radiative transfer of electronic excitation energy. The kinetic and thermodynamic parameters of the redistribution of dyes DiO and DiI between NCs that was associated with the destruction of NC/DiO and NC/DiI complexes and the formation of new NC/(DiO + DiI) complexes were evaluated. Rate constants for the destruction of the complexes (K), lifetimes of the complexes (τ1/2), the activation energy for the destruction ( E a), the equilibrium constant ( K eq), and the change of free energy (Δ G 0), enthalpy (Δ H 0), and entropy (Δ S 0) of the process were calculated. The obtained kinetic parameters pointed to high kinetic stability for all investigated complexes whereas the thermodynamic ones indicated that dye redistribution required high temperatures.

  15. Matrix Metalloprotease 2-Responsive Multifunctional Liposomal Nanocarrier for Enhanced Tumor Targeting

    PubMed Central

    Zhu, Lin; Kate, Pooja; Torchilin, Vladimir P.

    2012-01-01

    A novel “smart” multifunctional drug delivery system was successfully developed to respond to the up-regulated matrix metalloprotease 2 (MMP2) in the tumor microenvironment and improve cancer cell-specific delivery of loaded drugs. The system represents a surface-functionalized liposomal nanocarrier, for which two functional polyethylene glycol (PEG)-lipid conjugates were synthesized and characterized. The functionalized liposome was further modified with the tumor cell-specific anti-nucleosome monoclonal antibody (mAb 2C5). In the resulting system, several drug delivery strategies were combined in the same nanocarrier in a simple way and coordinated in an optimal fashion. The functions of the nanocarrier include: i) the hydrophilic and flexible long PEG chains to prevent nanocarrier non-specific interactions and prolong its circulation time; ii) a nanoscale size of the system that allows for its passive tumor targeting via the enhanced permeability and retention (EPR) effect; iii) a mAb 2C5 to allow for the specific targeting of tumor cells; iv) a matrix metalloprotease 2-sensitive bond between PEG and lipid that undergoes cleavage in the tumor by the highly expressed extracellular MMP2 for the removal of PEG chains; v) The cell-penetrating peptide (TATp) triggering of the enhanced intracellular delivery of the system after long-chain PEG removal and exposure of the previously hidden surface-attached TATp. It is shown that such a design can enhance the targetability and internalization of nanocarriers in cancer cells. PMID:22409425

  16. The in vitro biocompatibility of self-assembled hyperbranched copolyphosphate nanocarriers.

    PubMed

    Liu, Jinyao; Huang, Wei; Pang, Yan; Zhu, Xinyuan; Zhou, Yongfeng; Yan, Deyue

    2010-07-01

    Polymeric micelles are recognized as very promising nanocarriers for small-molecule drugs, DNA, and proteins delivery. Polyphosphates are an important class of eminent biomaterials and widely used in biomedicine due to their good biocompatibility, biodegradability, and flexibility in adjusting the pendant structures. Here, some full-polyphosphate nanocarriers have been constructed successfully through self-assembly of amphiphilic hyperbranched multiarm copolymers (denoted as HPHEEP-star-PPEPs). The hydrophilic core and hydrophobic multiarm of HPHEEP-star-PPEPs are composed by hyperbranched and linear polyphosphates respectively. HPHEEP-star-PPEPs can self-assembly into nanocarriers in aqueous media with controlled size from 48 to 74 nm by conveniently adjusting the length of hydrophobic arm. These nanocarriers possess excellent biocompatibility against NIH 3T3 cells and are easily internalized by vivid cells. Chlorambucil-loaded nanocarriers were investigated for proliferation inhibition of an MDA-MB-231 breast cancer cell line in vitro, and the chlorambucil dose required for 50% cellular growth inhibition was found to be 3 microg/mL. PMID:20417961

  17. Matrix metalloprotease 2-responsive multifunctional liposomal nanocarrier for enhanced tumor targeting.

    PubMed

    Zhu, Lin; Kate, Pooja; Torchilin, Vladimir P

    2012-04-24

    A novel "smart" multifunctional drug delivery system was successfully developed to respond to the up-regulated matrix metalloprotease 2 (MMP2) in the tumor microenvironment and improve cancer cell-specific delivery of loaded drugs. The system represents a surface-functionalized liposomal nanocarrier, for which two functional polyethylene glycol (PEG)-lipid conjugates were synthesized and characterized. The functionalized liposome was further modified with the tumor cell-specific antinucleosome monoclonal antibody (mAb 2C5). In the resulting system, several drug delivery strategies were combined in the same nanocarrier in a simple way and coordinated in an optimal fashion. The functions of the nanocarrier include (i) the hydrophilic and flexible long PEG chains to prevent nanocarrier nonspecific interactions and prolong its circulation time; (ii) a nanoscale size of the system that allows for its passive tumor targeting via the enhanced permeability and retention (EPR) effect; (iii) a mAb 2C5 to allow for the specific targeting of tumor cells; (iv) a matrix metalloprotease 2-sensitive bond between PEG and lipid that undergoes cleavage in the tumor by the highly expressed extracellular MMP2 for the removal of PEG chains; (v) cell-penetrating peptide (TATp) triggering of the enhanced intracellular delivery of the system after long-chain PEG removal and exposure of the previously hidden surface-attached TATp. It is shown that such a design can enhance the targetability and internalization of nanocarriers in cancer cells. PMID:22409425

  18. Nanotherapeutics of PTEN Inhibitor with Mesoporous Silica Nanocarrier Effective for Axonal Outgrowth of Adult Neurons.

    PubMed

    Kim, Min Soo; El-Fiqi, Ahmed; Kim, Jong-Wan; Ahn, Hong-Sun; Kim, Hyukmin; Son, Young-Jin; Kim, Hae-Won; Hyun, Jung Keun

    2016-07-27

    Development of therapeutic strategies such as effective drug delivery is an urgent and yet unmet need for repair of damaged nervous systems. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) regulates axonal regrowth of central and peripheral nervous systems; its inhibition, meanwhile, facilitates axonal outgrowth of injured neurons. Here we show that nanotherapeutics based on mesoporous silica nanoparticles loading PTEN-inhibitor bisperoxovanadium (BpV) are effective for delivery of drug molecules and consequent improvement of axonal outgrowth. Mesoporous nanocarriers loaded BpV drug at large amount (27 μg per 1 mg of carrier), and released sustainably over 10 d. Nanocarrier-BpV treatment of primary neurons from the dorsal root ganglions (DRGs) of rats and mice at various concentrations induced them to actively take up the nanocomplexes with an uptake efficiency as high as 85%. The nanocomplex-administered neurons exhibited significantly enhanced axonal outgrowth compared with those treated with free-BpV drug. The expression of a series of proteins involved in PTEN inhibition and downstream signaling was substantially up-/down-regulated by the nanocarrier-BpV system. Injection of the nanocarriers into neural tissues (DRG, brain cortex, and spinal cord), moreover, demonstrated successful integration into neurons, glial cells, oligodendrocytes, and macrophages, suggesting the possible nanotherapeutics applications in vivo. Together, PTEN-inhibitor delivery via mesoporous nanocarriers can be considered a promising strategy for stimulating axonal regeneration in central and peripheral nervous systems. PMID:27386893

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

    PubMed

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

    2016-08-24

    Smart drug delivery systems (DDSs) have attracted the attention of many scientists, as carriers that can be stimulated by changes in environmental parameters such as temperature, pH, light, electromagnetic fields, mechanical forces, etc. These smart nanocarriers can release their cargo on demand when their target is reached and the stimulus is applied. Using the techniques of nanotechnology, these nanocarriers can be tailored to be target-specific, and exhibit delayed or controlled release of drugs. Temperature-responsive nanocarriers are one of most important groups of smart nanoparticles (NPs) that have been investigated during the past decades. Temperature can either act as an external stimulus when heat is applied from the outside, or can be internal when pathological lesions have a naturally elevated termperature. A low critical solution temperature (LCST) is a special feature of some polymeric materials, and most of the temperature-responsive nanocarriers have been designed based on this feature. In this review, we attempt to summarize recent efforts to prepare innovative temperature-responsive nanocarriers and discuss their novel applications. PMID:27349465

  20. Biocompatible nanocarrier fortified with a dipyridinium-based amphiphile for eradication of biofilm.

    PubMed

    Goswami, Sudeep; Thiyagarajan, Durairaj; Das, Gopal; Ramesh, Aiyagari

    2014-09-24

    Annihilation of bacterial biofilms is challenging owing to their formidable resistance to therapeutic antibiotics and thus there is a constant demand for development of potent antibiofilm agents that can abolish established biofilms. In the present study, the activity of a dipyridinium-based cationic amphiphile (compound 1) against established bacterial biofilms and the subsequent development of a compound 1-loaded nanocarrier for potential antibiofilm therapy are highlighted. Solution-based assays and microscopic analysis revealed the antagonistic effect of compound 1 on biofilms formed by Staphylococcus aureus MTCC 96 and Pseudomonas aeruginosa MTCC 2488. In combination studies, compound 1 could efficiently potentiate the action of tobramycin and gentamicin on P. aeruginosa and S. aureus biofilm, respectively. A human serum albumin (HSA)-based nanocarrier loaded with compound 1 was generated, which exhibited sustained release of compound 1 at physiological pH. The compound 1-loaded HSA nanocarrier (C1-HNC) displayed the signature membrane-directed activity of the amphiphile on target bacteria, efficiently eliminated established bacterial biofilms, and was observed to be nontoxic to a model human cell line. Interestingly, compound 1 as well as the amphiphile-loaded HSA nanocarrier could eradicate established S. aureus biofilm from the surface of a Foley's urinary catheter. On the basis of its biocompatibility and high antibiofilm activity, it is conceived that the amphiphile-loaded nanocarrier may hold potential in antibiofilm therapy. PMID:25162678

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

    NASA Astrophysics Data System (ADS)

    Zhao, Mei-Xia; Zhu, Bing-Jie

    2016-04-01

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

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

    PubMed

    Zhao, Mei-Xia; Zhu, Bing-Jie

    2016-12-01

    Quantum dots (QDs), nano-carriers for drugs, can help realize the targeting of drugs, and improve the bioavailability of drugs in biological fields. And, a QD nano-carrier system for drugs has the potential to realize early detection, monitoring, and localized treatments of specific disease sites. In addition, QD nano-carrier systems for drugs can improve stability of drugs, lengthen circulation time in vivo, enhance targeted absorption, and improve the distribution and metabolism process of drugs in organization. So, the development of QD nano-carriers for drugs has become a hotspot in the fields of nano-drug research in recent years. In this paper, we review the advantages and applications of the QD nano-carriers for drugs in biological fields. PMID:27090658

  3. Enhanced protein delivery by multi-ion containing eggshell derived apatitic-alginate composite nanocarriers.

    PubMed

    Sampath Kumar, T S; Madhumathi, K; Rajkamal, B; Zaheatha, S; Rajathi Malar, A; Alamelu Bai, S

    2014-11-01

    Eggshell is an attractive natural source of calcium for the synthesis of hydroxyapatite (HA) as it contains minor amounts of biologically relevant elements such as Mg, Sr, and Si. The mineral phase of the human bone is essentially a calcium deficient hydroxyapatite (CDHA) which shows more bioactivities and absorbance than stoichiometric HA does. Hence, we have attempted to develop a protein delivery system based on eggshell derived CDHA (ECDHA) nanoparticles for bone tissue engineering. Nanoparticles with Ca/P molar ratio of 1.67, 1.61 and 1.51 to form CDHAs with compositions covering the properties of stable HA phase (Ca/P=1.67) to degradable tricalcium phosphate (TCP) phase (Ca/P=1.5) were synthesized by microwave-accelerated wet chemical synthesis using eggshell as well as synthetic calcium hydroxide as calcium precursors. The delivery profiles of bovine serum albumin (BSA), a model protein by the nanocarriers, were studied. Both eggshells derived and synthetic CDHA samples showed maximum amount of loading of 57% and 37%, respectively at a Ca/P ratio of 1.51, comparing to stoichiometric HA. ECDHA also showed a much more BSA release (25%) than synthetically derived CDHA (6.5%) did. To further improve the release profile, alginate coating was carried out on CDHA nanoparticles and the BSA release profiles were evaluated. A maximum release of 65% was observed for alginate coated ECDHA at a Ca/P ratio of 1.51 for a period of 2 days. The ECDHA nanoparticle with a Ca/P ratio similar to degradable TCP and with alginate coating seems to be an ideal protein delivery agent. PMID:25444657

  4. Nanocarrier for Oral Peptide Delivery Produced by Polyelectrolyte Complexation in Nanoconfinement.

    PubMed

    He, Wei; Parowatkin, Maria; Mailänder, Volker; Flechtner-Mors, Marion; Graf, Robert; Best, Andreas; Koynov, Kaloian; Mohr, Kristin; Ziener, Ulrich; Landfester, Katharina; Crespy, Daniel

    2015-08-10

    The hydrophilic peptide YY (PYY) is a promising hormone-based antiobesity drug. We present a new concept for the delivery of PYY from pH-responsive chitosan-based nanocarriers. To overcome the drawbacks while retaining the merits of the polyelectrolyte complex (PEC) method, we propose a one-pot approach for the encapsulation of a hydrophilic peptide drug in cross-linked PEC nanocarriers. First, the hydrophilic peptide is encapsulated via polyelectrolyte complexation within water-in-oil miniemulsion droplets. In a second step, the PEC surface is reinforced by controlled interfacial cross-linking. PYY is efficiently encapsulated and released upon pH change. Such nanocarriers are promising candidates for the fight against obesity and, in general, for the oral delivery of protein drugs. PMID:26161672

  5. Linear-g-hyperbranched and cyclodextrin-based amphiphilic block copolymer as a multifunctional nanocarrier.

    PubMed

    Zhao, Yamei; Tian, Wei; Yang, Guang; Fan, Xiaodong

    2014-01-01

    In this paper, a novel, multifunctional polymer nanocarrier was designed to provide adequate volume for high drug loading, to afford a multiregion encapsulation ability, and to achieve controlled drug release. An amphiphilic, triblock polymer (ABC) with hyperbranched polycarbonsilane (HBPCSi) and β-cyclodextrin (β-CD) moieties were first synthesized by the combination of a two-step reversible addition-fragmentation transfer polymerization into a pseudo-one-step hydrosilylation and quaternization reaction. The ABC then self-assembled into stable micelles with a core-shell structure in aqueous solution. These resulting micelles are multifunctional nanocarriers which possess higher drug loading capability due to the introduction of HBPCSi segments and β-CD moieties, and exhibit controlled drug release based on the diffusion release mechanism. The novel multifunctional nanocarrier may be applicable to produce highly efficient and specialized delivery systems for drugs, genes, and diagnostic agents. PMID:25550733

  6. Soybean agglutinin-conjugated silver nanoparticles nanocarriers in the treatment of breast cancer cells.

    PubMed

    Casañas Pimentel, Rocio Guadalupe; Robles Botero, Viviana; San Martín Martínez, Eduardo; Gómez García, Consuelo; Hinestroza, Juan Paulo

    2016-01-01

    Silver nanoparticles (AgNPs) induce diverse cell-death mechanisms, similar to those promoted by anticancer chemotherapeutics; however, they have not been tested in vivo because their action is not limited to cancer cells. Therefore, in vivo evaluations of their effectiveness should be developed with targeting systems. Breast cancer shows changes in the sugar expression patterns on cell surfaces, related to cancer progression and metastases; those changes have been identified previously by the specific binding of soybean agglutinin (SBA). Here is proposed the use of SBA to target the AgNP activity in breast cancer. For that, the present work reports the synthesis of AgNPs (3.89 ± 0.90 nm) through the polyol method, the generation of AgNP nanocarriers, and the bioconjugation protocol of the nanocarrier with SBA. The free AgNPs, the AgNP nanocarriers, and the SBA-bioconjugated AgNP nanocarriers were tested for cytotoxicity in breast cancerous (MDA-MB-231and MCF7) and non cancerous (MCF 10A) cells, using the MTT assay. AgNPs demonstrated cytotoxic activity in vitro, the non cancerous cells (MCF 10A) being more sensible than the cancerous cells (MDA-MB-231 and MCF7) showing LD(50) values of 128, 205, and 319 μM Ag, respectively; the nanoencapsulation decreased the cytotoxic effect of AgNPs in non cancerous cells, maintaining or increasing the effect on the cancer-derived cells, whereas the SBA-bioconjugation allowed AgNP cytotoxic activity with a similar behavior to the nanocarriers. Future experiments need to be developed to evaluate the targeting effect of the SBA-bioconjugated AgNP nanocarriers to study their functionality in vivo. PMID:26540350

  7. Hyaluronidase Embedded in Nanocarrier PEG Shell for Enhanced Tumor Penetration and Highly Efficient Antitumor Efficacy.

    PubMed

    Zhou, Hao; Fan, Zhiyuan; Deng, Junjie; Lemons, Pelin K; Arhontoulis, Dimitrios C; Bowne, Wilbur B; Cheng, Hao

    2016-05-11

    One of the major challenges in applying nanomedicines to cancer therapy is their low interstitial diffusion in solid tumors. Although the modification of nanocarrier surfaces with enzymes that degrade extracellular matrix is a promising strategy to improve nanocarrier diffusion in tumors, it remains challenging to apply this strategy in vivo via systemic administration of nanocarriers due to biological barriers, such as reduced blood circulation time of enzyme-modified nanocarriers, loss of enzyme function in vivo, and life-threatening side effects. Here, we report the conjugation of recombinant human hyaluronidase PH20 (rHuPH20), which degrades hyaluronic acid, on the surfaces of poly(lactic-co-glycolic acid)-b-polyethylene glycol (PLGA-PEG) nanoparticles followed by anchoring a relatively low density layer of PEG, which reduces the exposure of rHuPH20 for circumventing rHuPH20-mediated clearance. Despite the extremely short serum half-life of rHuPH20, our unique design maintains the function of rHuPH20 and avoids its effect on shortening nanocarrier blood circulation. We also show that rHuPH20 conjugated on nanoparticles is more efficient than free rHuPH20 in facilitating nanoparticle diffusion. The facile surface modification quadruples the accumulation of conventional PLGA-PEG nanoparticles in 4T1 syngeneic mouse breast tumors and enable their uniform tumor distribution. The rHuPH20-modified nanoparticles encapsulating doxorubicin efficiently inhibit the growth of aggressive 4T1 tumors under a low drug dose. Thus, our platform technology may be valuable to enhance the clinical efficacy of a broad range of drug nanocarriers. This study also provides a general strategy to modify nanoparticles with enzymes that otherwise may reduce nanoparticle circulation or lose function in the blood. PMID:27057591

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  10. A novel assay for monitoring internalization of nanocarrier coupled antibodies

    PubMed Central

    Nielsen, Ulrik B; Kirpotin, Dmitri B; Pickering, Edward M; Drummond, Daryl C; Marks, James D

    2006-01-01

    Background Discovery of tumor-selective antibodies or antibody fragments is a promising approach for delivering therapeutic agents to antigen over-expressing cancers. Therefore it is important to develop methods for the identification of target- and function specific antibodies for effective drug delivery. Here we describe a highly selective and sensitive method for characterizing the internalizing potential of multivalently displayed antibodies or ligands conjugated to liposomes into tumor cells. The assay requires minute amounts of histidine-tagged ligand and relies on the non-covalent coupling of these antibodies to fluorescent liposomes containing a metal ion-chelating lipid. Following incubation of cells with antibody-conjugated liposomes, surface bound liposomes are gently removed and the remaining internalized liposomes are quantitated based on fluorescence in a high throughput manner. We have termed this methodology "Chelated Ligand Internalization Assay", or CLIA. Results The specificity of the assay was demonstrated with different antibodies to the ErbB-2 and EGF receptors. Antibody-uptake correlated with receptor expression levels in tumor cell lines with a range of receptor expression. Furthermore, Ni-NTA liposomes containing doxorubicin were used to screen for the ability of antibodies to confer target-specific cytotoxicity. Using an anti-ErbB2 single chain Fv (scFv) (F5) antibody, cytotoxicity could be conferred to ErbB2-overexpressing cells; however, a poly(ethylene glycol)-linked lipid (DSPE-PEG-NTA-Ni) was necessary to allow for efficient loading of the drug and to reduce nonspecific drug leakage during the course of the assay. Conclusion The CLIA method we describe here represents a rapid, sensitive and robust assay for the identification and characterization of tumor-specific antibodies capable of high drug-delivery efficiency when conjugated to liposomal nanocarriers. PMID:17014727

  11. Lecithin-gold hybrid nanocarriers as efficient and pH selective vehicles for oral delivery of diacerein-In-vitro and in-vivo study.

    PubMed

    Javed, Ibrahim; Hussain, Syed Zajif; Shahzad, Atif; Khan, Jahanzeb Muhammad; Ur-Rehman, Habib; Rehman, Mubashar; Usman, Faisal; Razi, Muhammad Tahir; Shah, Muhammad Raza; Hussain, Irshad

    2016-05-01

    We report the synthesis and evaluation of lecithin-gold hybrid nanocarriers for the oral delivery of drugs with improved pharmacokinetics, Au-drug interactive bioactivity and controlled drug releasing behavior at physiological pH inside human body. For this purpose, diacerein, a hydrophobic anti-arthritic drug, was loaded in lecithin NPs (LD NPs), which were further coated by Au NPs either by in-situ production of Au NPs on LD NPs or by employing pre-synthesized Au NPs. All LDAu NPs were found to release drug selectively at the physiological pH of 7.4 and showed 2.5 times increase in the oral bioavailability of diacerein. Pharmacological efficacy was significantly improved i.e., greater than the additive effect of diacerein and Au NPs alone. LDAu NPs started suppressing inflammation at first phase, whereas LD NPs showed activity in the second phase of inflammation. These results indicate the interaction of Au NPs with prostaglandins and histaminic mediators of first phase of carrageenan induced inflammation. Acute toxicity study showed no hepatic damage but the renal toxicity parameters were close to the upper safety limits. Toxicity parameters were dependent on surface engineering of LDAu NPs. Apart from enhancing the oral bioavailability of hydrophobic drugs and improving their anti-inflammatory activity, these hybrid nanocarriers may have potential applications in gold-based photothermal therapy and the tracing of inflammation at atherosclerotic and arthritic site. PMID:26816348

  12. Robust two-photon visualized nanocarrier with dual targeting ability for controlled chemo-photodynamic synergistic treatment of cancer.

    PubMed

    Wan, Hao; Zhang, Yi; Zhang, Weibing; Zou, Hanfa

    2015-05-13

    In consideration of the intrinsic complexity of cancer, just being a delivery nanovehicle for the nanocarrier is no longer enough to fulfill requirements of dealing with cancer. In this regard, the multifunctional nanocarrier appears to be an appealing choice in cancer treatment. Herein, the novel multifunctional nanocarrier (Fe3O4-NS-C3N4@mSiO2-PEG-RGD) possessing properties of dual targeting (the peptide- and magnetism-mediated targeting), imaging (one- and two-photon modes), pH-triggered release of loaded anticancer drug, and synergistic treatment (photodynamic therapy (PDT) combined with chemotherapy) are successfully developed. The nanocarrier specifically centralizes within cancer cells with the enhanced amount through the dual targeting ability and is facilely tracked under one- and two-photon imaging modes attributed to the autofluorescence. Then, visible light irradiation-induced PDT combined with low pH-triggered chemotherapy synergistically cooperate to efficiently kill cancer cells. Following the above process, the multifunctional nanocarrier demonstrates effective inhibition of the growth of A549 and HeLa cancer cells. The efficient manipulation of Fe3O4-NS-C3N4@mSiO2-PEG-RGD also implies potential applications of the multifunctional nanocarrier in delivery of different agents. Furthermore, it might also broaden the scope of fabrication of the multifunctional nanocarrier for inhibiting the growth of cancer cells. PMID:25893951

  13. Engine

    SciTech Connect

    Shin, H.B.

    1984-02-28

    An internal combustion engine has a piston rack depending from each piston. This rack is connected to a power output shaft through a mechanical rectifier so that the power output shaft rotates in only one direction. A connecting rod is pivotally connected at one end to the rack and at the other end to the crank of a reduced function crankshaft so that the crankshaft rotates at the same angular velocity as the power output shaft and at the same frequency as the pistons. The crankshaft has a size, weight and shape sufficient to return the pistons back into the cylinders in position for the next power stroke.

  14. Synthesis of hetero-polymer functionalized nanocarriers by combining surface-initiated ATRP and RAFT polymerization.

    PubMed

    Huang, Xin; Hauptmann, Nicole; Appelhans, Dietmar; Formanek, Petr; Frank, Simon; Kaskel, Stefan; Temme, Achim; Voit, Brigitte

    2012-12-01

    Smart nanocarriers are created based on a bi-functional hetero-initiator for RAFT and ATRP technique, bi-functionalizing mesoporous silica nanoparticles with two polymer types. The pH-dependent behavior of PDEAEMA as the gatekeeper polymer is verified by electrokinetic measurements and a controlled release behavior is demonstrated using doxorubicin as the drug. PMID:22911545

  15. Folate-targeting magnetic core-shell nanocarriers for selective drug release and imaging.

    PubMed

    Wang, Hanjie; Wang, Sheng; Liao, Zhenyu; Zhao, Peiqi; Su, Wenya; Niu, Ruifang; Chang, Jin

    2012-07-01

    One of the most urgent medical requirements for cancer diagnosis and treatment is how to construct a multifunctional vesicle for simultaneous diagnostic imaging and therapeutic applications. In our study, superparamagnetic iron oxide nanocrystals (SPIONs) and doxorubicin hydrochloride (DOX) are co-encapsulated into PLGA/polymeric liposome core-shell nanocarriers for achieving simultaneous magnetic resonance imaging and targeting drug delivery. The core-shell nanocarrier was self-assembled from a hydrophobic PLGA core and a hydrophilic folate coated PEGlated lipid shell. The experiment showed that folate-targeting magnetic core-shell nanocarriers show clear core-shell structure, excellent magnetism and controlled drug release behavior. Importantly, the core-shell nanoparticles achieve the possibility of co-delivering drugs and SPIONs to the same cells for enhancing magnetic resonance imaging (MRI) effect and improving drug delivery efficiency simultaneously. Our data suggests that the folate-targeting magnetic core-shell nanocarriers (FMNs) could provide effective cancer-targeting and MRI as well as drug delivery. The FMNs may become a useful nanomedical carrier system for cancer diagnosis and treatment. PMID:22525087

  16. Temporal Multiscale Approach for Nanocarrier Motion with Simultaneous Adhesion and Hydrodynamic Interactions in Targeted Drug Delivery

    PubMed Central

    Radhakrishnan, R.; Uma, B.; Liu, J.; Ayyaswamy, P. S.; Eckmann, D. M.

    2012-01-01

    We present a fluctuating hydrodynamics approach and a hybrid approach combining fluctuating hydrodynamics with generalized Langevin dynamics to resolve the motion of a nanocarrier when subject to both hydrodynamic interactions and adhesive interactions. Specifically, using these approaches, we compute equilibrium probability distributions at constant temperature as well as velocity autocorrelation functions of the nanocarrier subject to thermal motion in a quiescent Newtonian fluid medium, when tethered by a harmonic spring force mimicking a tether due to a single receptor-ligand bond. We demonstrate that the thermal equipartition of translation, rotation, and spring degrees of freedom are preserved by our formalism while simultaneously resolving the nature of the hydrodynamic correlations. Additionally, we evaluate the potential of mean force (or free energy density) along a specified reaction coordinate to faciltate extensive conformational sampling of the nanocarrier motion. We show that our results are in excellent agreement with analytical results and Monte Carlo simulations, thereby validating our methodologies. The frameworks we have presented provide a comprehensive platform for temporal multiscale modeling of hydrodynamic and microscopic interactions mediating nanocarrier motion and adhesion in vascular targeted drug delivery. PMID:23853388

  17. Nanocarrier with self-antioxidative property for stabilizing and delivering ascorbyl palmitate into skin.

    PubMed

    Janesirisakule, Sirinapa; Sinthusake, Tarit; Wanichwecharungruang, Supason

    2013-08-01

    The concept of a nanocarrier with a self-antioxidative property to deliver and stabilize a labile drug while at the same time providing a free radical scavenging activity is demonstrated. Curcumin was grafted onto a poly(vinyl alcohol) [PV(OH)] chain, and the nanocarriers fabricated from the obtained curcumin-grafted PV(OH) polymer [CUR-PV(OH)] showed a good free radical scavenging activity. Ascorbyl palmitate (AP) could be effectively loaded into the CUR-PV(OH) at 29% by weight. The CUR-PV(OH)-encapsulated AP was 77% more stable than the free (unencapsulated) AP, and 47% more stable than AP encapsulated in the control nanocarrier with no antioxidative property [cinnamoyl-grafted PV(OH); CIN-PV(OH)]. Although coencapsulation of curcumin and AP into CIN-PV(OH) showed some improvement on the AP stability, AP was more stable when encapsulated in CUR-PV(OH). Compared with the free AP, encapsulated AP within the CUR-PV(OH) nanocarriers showed not only a better penetration into pig skin dermis via hair follicle pathway followed by the release and diffusion of the AP, but also a greater AP stability after skin application. Although a proof of principle is shown for CUR-PV(OH) and AP, it is likely that other carriers of the same principal could be designed and applied to different oxidation-sensitive drugs. PMID:23775704

  18. The Supramolecular Organization of a Peptide-Based Nanocarrier at High Molecular Detail.

    PubMed

    Rad-Malekshahi, Mazda; Visscher, Koen M; Rodrigues, João P G L M; de Vries, Renko; Hennink, Wim E; Baldus, Marc; Bonvin, Alexandre M J J; Mastrobattista, Enrico; Weingarth, Markus

    2015-06-24

    Nanovesicles self-assembled from amphiphilic peptides are promising candidates for applications in drug delivery. However, complete high-resolution data on the local and supramolecular organization of such materials has been elusive thus far, which is a substantial obstacle to their rational design. In the absence of precise information, nanovesicles built of amphiphilic "lipid-like" peptides are generally assumed to resemble liposomes that are organized from bilayers of peptides with a tail-to-tail ordering. Using the nanocarrier formed by the amphiphilic self-assembling peptide 2 (SA2 peptide) as an example, we derive the local and global organization of a multimega-Dalton peptide-based nanocarrier at high molecular detail and at close-to physiological conditions. By integrating a multitude of experimental techniques (solid-state NMR, AFM, SLS, DLS, FT-IR, CD) with large- and multiscale MD simulations, we show that SA2 nanocarriers are built of interdigitated antiparallel β-sheets, which bear little resemblance to phospholipid liposomes. Our atomic level study allows analyzing the vesicle surface structure and dynamics as well as the intermolecular forces between peptides, providing a number of potential leads to improve and tune the biophysical properties of the nanocarrier. The herein presented approach may be of general utility to investigate peptide-based nanomaterials at high-resolution and at physiological conditions. PMID:26022089

  19. Multifunctional Micellar Nanocarriers for Tumor-Targeted Delivery of Hydrophobic Drugs.

    PubMed

    Dai, Zhi; Tu, Ying; Zhu, Lin

    2016-06-01

    Poor water solubility, low tumor specificity, insufficient cell internalization, and drug resistance are typical among chemotherapy drugs. In this study, the multifunctional micellar nanocarriers containing the PEG2k-pp-PE, a matrix metalloproteinase 2 (MMP2)-labile self-assembling block copolymer, and the TAT-PEG1k-PE, a cell penetrating moiety, were developed for tumor-targeted delivery of hydrophobic drugs. The functional polymers and their nanocarriers were characterized in terms of their size, zeta potential, micelle formation capability, drug loading and release, cellular uptake, and anticancer activity. After the MMP2-mediated cleavage, the protective long chain PEG (PEG2k) was deshielded and the cell penetrating peptide (TAT) was exposed for the enhanced tumor targeting and cellular penetration. In the in vitro studies, the multifunctional nanocarriers showed the improved cellular uptake and anticancer activity in various cancer cells including both drug sensitive and resistant cells, compared to their nonsensitive counterparts and conventional polymeric micelles. Furthermore, the PEG2k-pp-PE and its containing micelles were found to possess the capability to reverse the P-glycoprotein-mediated multidrug resistance. Our results suggested that the multifunctional micellar nanocarriers would be a promising tumor-targeted drug delivery platform, applicable for the MMP2 up-regulated cancers. PMID:27319214

  20. High-efficient nano-carrier gel systems for testosterone propionate skin delivery.

    PubMed

    Meng, Shu; Chen, Zaixing; Yang, Liqun; Zhang, Xiaowei; Guo, Jing; Li, Miao; Li, Jianxin

    2015-01-01

    The purpose of the current investigation was to evaluate the skin delivery potential of the different nano-carrier gels including liposomal gel, ethosomal gel and microemulsion gel bearing testosterone propionate (TP) as a testosterone deficient therapy. The prepared nano-particles were characterized for their shape, particle size distribution and zeta potential. In vitro skin permeation and in vivo transdermal delivery of nano-carrier gels were studied with the Franz diffusion cells and confocal laser scanning microscopy (CLSM). The results showed that all of nano-particles were almost spherical with low polydispersity and nano-metric size range from 40 to 200 nm. TP ethosomal gel also provided an enhanced transdermal flux of 7.64 ± 1.4 μg/cm(2)/h and a decreased lag time of 0.69 h across rat skin as compared with the other two formulations. The skin penetration efficiency of TP nano-carrier gels also revealed that TP ethosomal gel would enhanced penetration of rhodamine red (RR)-loaded formulation to the deeper layers of the skin (268 µm) than the liposomal gel (192 µm) and microemulsion gel (228 µm). This study demonstrated TP ethosomal gel is a promising nano-carrier for delivering TP through the skin. PMID:24799076

  1. Adequately-Sized Nanocarriers Allow Sustained Targeted Drug Delivery to Neointimal Lesions in Rat Arteries.

    PubMed

    Taniguchi, Ryosuke; Miura, Yutaka; Koyama, Hiroyuki; Chida, Tsukasa; Anraku, Yasutaka; Kishimura, Akihiro; Shigematsu, Kunihiro; Kataoka, Kazunori; Watanabe, Toshiaki

    2016-06-01

    In atherosclerotic lesions, the endothelial barrier against the bloodstream can become compromised, resulting in the exposure of the extracellular matrix (ECM) and intimal cells beneath. In theory, this allows adequately sized nanocarriers in circulation to infiltrate into the intimal lesion intravascularly. We sought to evaluate this possibility using rat carotid arteries with induced neointima. Cy5-labeled polyethylene glycol-conjugated polyion complex (PIC) micelles and vesicles, with diameters of 40, 100, or 200 nm (PICs-40, PICs-100, and PICs-200, respectively) were intravenously administered to rats after injury to the carotid artery using a balloon catheter. High accumulation and long retention of PICs-40 in the induced neointima was confirmed by in vivo imaging, while the accumulation of PICs-100 and PICs-200 was limited, indicating that the size of nanocarriers is a crucial factor for efficient delivery. Furthermore, epirubicin-incorporated polymeric micelles with a diameter similar to that of PICs-40 showed significant curative effects in rats with induced neointima, in terms of lesion size and cell number. Specific and effective drug delivery to pre-existing neointimal lesions was demonstrated with adequate size control of the nanocarriers. We consider that this nanocarrier-based drug delivery system could be utilized for the treatment of atherosclerosis. PMID:27183493

  2. Optimal Structural Design of Mannosylated Nanocarriers for Macrophage Targeting

    PubMed Central

    Chen, Peiming; Zhang, Xiaoping; Jia, Lee; Prud’homme, Robert K.; Szekely, Zoltan; Sinko, Patrick J.

    2014-01-01

    Macrophages are involved in a number of diseases, such as HIV infection/AIDS, tuberculosis, tumor development and atherosclerosis. Macrophages possess several cell surface receptors (e.g., the mannose receptor, MR) that may serve as drug delivery cellular portals for nanocarriers (NCs). In this study, the optimal structural configuration for cell uptake of mannosylated poly(ethylene glycol)-conjugate type NCs was determined. A series NCs was synthesized to systematically evaluate the effects of the number of mannose units (Man), the PEG carrier size and the mPEG spacer length between adjacent mannose units on NC uptake into MR-expressing J774.E murine macrophage-like cells. Among NCs with 0, 1, 2 or 4 units of mannose, the uptake of (Man)2-NC was the highest, suggesting a trade-off between avidity and NC-MR clustering on the cell surface that sterically hinders endocytosis. This optimal (Man)2-NC configuration was built into subsequent NCs to optimize the other two parameters, PEG carrier size and spacer length. NCs with 0, 5, 12, 20, 30 or 40 kDa linear PEG carriers showed an inverse relationship between PEG size and uptake. The 12 kDa PEG carrier was chosen for investigating the third parameter, the Man-Man distance, since it may represent the best trade off (i.e., tissue penetration vs. systemic clearance) for in vivo macrophage targeting. Three (Man)2-PEG12kDa NCs with different Man-Man distances (39, 56 or 89 Å) were synthesized. The uptake of the NC with the 56 Å distance between mannoses was four- and two-fold higher than NCs with 39 Å and 89 Å distances, respectively. Confocal microscopy confirmed that the optimized (Man)2-PEG12kDa NC with the 56 Å Man-Man distance was internalized via endocytosis consistent with temperature-dependent active uptake. In conclusion, the optimal NC structural parameters for targeting the MR on macrophage-like J774.E cells are (i) a small PEG polymer carrier, (ii) two mannose units per NC and (iii) a 56 Å distance between

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

    PubMed

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

    2015-02-01

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

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

    PubMed

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

    2016-05-01

    Simultaneous inhibition of IL4 and IL13 via the common receptor chain IL4Rα to block adequately their biologic effects presents a promising therapeutic approach to give the additional relief required for asthma patients. In this study, superparamagnetic iron oxide nanoparticles were conjugated with anti-IL4Rα blocking antibodies via polyethylene glycol (PEG) polymers. The delivery of these blocking antibodies to the inflammatory sites in the lung via the developed nanocarriers was assessed using noninvasive free-breathing pulmonary MRI. Biocompatibility assays confirmed the safety of the developed nanocarriers for pre-clinical investigations. For all the investigated formulations, nanocarriers were found to be very stable at neutral pH. However, the stability noticeably decreased with the PEG length in acidic environment and thus the loaded antibodies were preferentially released. Immunofluorescence and fluorimetry assays confirmed the binding of the nanocarriers to the IL4Rα asthma biomarker. Pulmonary MRI performed using an ultra-short echo time sequence allowed simultaneous noninvasive monitoring of inflammatory responses induced by ovalbumin challenge and tracking of the developed nanocarriers, which were found to colocalize with the inflammatory sites in the lung. Targeting of the developed nanocarriers to areas rich in IL4Rα positive inflammatory cells was confirmed using histological and flow cytometry analyses. The anti-IL4Rα-conjugated nanocarriers developed here have been confirmed to be efficient in targeting key inflammatory cells during chronic lung inflammation following intrapulmonary administration. Targeting efficiency was monitored using noninvasive MRI, allowing detection of the nanocarriers' colocalizations with the inflammatory sites in the lung of ovalbumin-challenged asthmatic mice. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26708935

  5. Self-assembly behaviors of thermal- and pH- sensitive magnetic nanocarriers for stimuli-triggered release

    PubMed Central

    2014-01-01

    In the present work, we prepare thermo- and pH-sensitive polymer-based nanoparticles incorporating with magnetic iron oxide as the remote-controlled, stimuli-response nanocarriers. Well-defined, dual functional tri-block copolymer poly[(acrylic acid)-block-(N-isopropylacrylamide)-block-(acrylic acid)], was synthesized via reversible addition-fragmentation chain-transfer (RAFT) polymerization with S,S′-bis(α,α′-dimethyl-α″-acetic acid)trithiocarbonate (CMP) as a chain transfer agent (CTA). With the aid of using 3-aminopropyltriethoxysilane, the surface-modified iron oxides, Fe3O4-NH2, was then attached on the surface of self-assembled tri-block copolymer micelles via 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride/N-hydroxysuccinamide (EDC/NHS) crosslinking method in order to furnish not only the magnetic resources for remote control but also the structure maintenance for spherical morphology of our nanocarriers. The nanocarrier was characterized by transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FT-IR), and ultraviolet–visible (UV/Vis) spectral analysis. Rhodamine 6G (R6G), as the modeling drugs, was encapsulated into the magnetic nanocarriers by a simple swelling method for fluorescence-labeling and controlled release monitoring. Biocompatibility of the nanocarriers was studied via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, which revealed that neither the pristine nanocarrier nor the R6G-loaded nanocarriers were cytotoxic to the normal fibroblast cells (L-929 cells). The in vitro stimuli-triggered release measurement showed that the intelligent nanocarriers were highly sensitive to the change of pH value and temperature rising by the high-frequency magnetic field (HFMF) treatment, which provided the significant potential to apply this technology to biomedical therapy by stimuli-responsive controlled release. PMID:25288914

  6. Targeting, Endocytosis, and Lysosomal Delivery of Active Enzymes to Model Human Neurons by ICAM-1-Targeted Nanocarriers

    PubMed Central

    Hsu, Janet; Hoenicka, Janet; Muro, Silvia

    2016-01-01

    Purpose Delivery of therapeutics to neurons is paramount to treat neurological conditions, including many lysosomal storage disorders. However, key aspects of drug-carrier behavior in neurons are relatively unknown: the occurrence of non-canonical endocytic pathways (present in other cells); whether carriers that traverse the blood-brain barrier are, contrarily, retained within neurons; if neuron-surface receptors are accessible to bulky carriers compared to small ligands; or if there are differences regarding neuronal compartments (neuron body vs. neurites) pertaining said parameters. We have explored these questions using model polymer nanocarriers targeting intercellular adhesion molecule-1 (ICAM-1). Methods Differentiated human neuroblastoma cells were incubated with anti-ICAM-coated polystyrene nanocarriers and analyzed by fluorescence microscopy. Results ICAM-1 expression and nanocarrier binding was enhanced in altered (TNFα) vs. control conditions. While small ICAM-1 ligands (anti-ICAM) preferentially accessed the cell body, anti-ICAM nanocarriers bound with faster kinetics to neurites, yet reached similar saturation over time. Anti-ICAM nanocarriers were also endocytosed with faster kinetics and lower saturation levels in neurites. Non-classical cell adhesion molecule (CAM) endocytosis ruled uptake, and neurite-to-cell body transport was inferred. Nanocarriers trafficked to lysosomes, delivering active enzymes (dextranase) with substrate reduction in a lysosomal-storage disease model. Conclusion ICAM-1-targeting holds potential for intracellular delivery of therapeutics to neurons. PMID:25319100

  7. Calcium phosphate hybrid nanoparticles: self-assembly formation, characterization, and application as an anticancer drug nanocarrier.

    PubMed

    Zhao, Xin-Yu; Zhu, Ying-Jie; Chen, Feng; Lu, Bing-Qiang; Qi, Chao; Zhao, Jing; Wu, Jin

    2013-06-01

    Calcium phosphate hybrid nanoparticles (CaP-HNPs) have been synthesized in aqueous solution through self-assembly by using two oppositely charged polyelectrolytes (poly(diallyldimethylammonium chloride) (PDADMAC) and poly(acrylate sodium) (PAS)) as dual templates. First, the PAS/Ca(2+) and PDADMAC/PO4(3-) complexes form through electrostatic interactions and then two complexes self-assemble into CaP-HNPs after mixing them together. The as-prepared CaP-HNPs exhibit a spherical morphology with a narrow size distribution, good dispersibility, and high colloidal stability in water. The CaP-HNPs are explored as a nanocarrier for the anticancer drug docetaxel (Dtxl). The CaP-HNPs show excellent biocompatibility, high drug-loading capacity, pH-sensitive drug-release behavior, and high anticancer effect after being loaded with Dtxl. Therefore, the as-prepared CaP-HNPs are promising drug nanocarriers for cancer therapy. PMID:23589508

  8. A functionalized fluorescent dendrimer as a pesticide nanocarrier: application in pest control

    NASA Astrophysics Data System (ADS)

    Liu, Xiaoxia; He, Bicheng; Xu, Zejun; Yin, Meizhen; Yang, Wantai; Zhang, Huaijiang; Cao, Jingjun; Shen, Jie

    2014-12-01

    We report the delivery of a hydrophobic pesticide, thiamethoxam, by water-soluble nanosized cationic dendrimers that contain hydrophobic dendritic polyesters and peripheral amines, demonstrated by DLS, spectral analysis and ITC. The dendrimer-based nanocarrier can efficiently deliver the pesticide into the live cells and largely increase the cytotoxicity of the drug.We report the delivery of a hydrophobic pesticide, thiamethoxam, by water-soluble nanosized cationic dendrimers that contain hydrophobic dendritic polyesters and peripheral amines, demonstrated by DLS, spectral analysis and ITC. The dendrimer-based nanocarrier can efficiently deliver the pesticide into the live cells and largely increase the cytotoxicity of the drug. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr05733c

  9. Cyclodextrin induced controlled delivery of a biological photosensitizer from a nanocarrier to DNA.

    PubMed

    Kundu, Pronab; Ghosh, Saptarshi; Das, Sinjan; Chattopadhyay, Nitin

    2016-02-01

    In this article, we have addressed to a demanding physicochemical aspect of therapeutic and drug research. We have reported a simple yet prospective technique that can be exploited for the controlled delivery of drugs and/or bioactive small molecules to the most relevant biomolecular target DNA. Exploiting various steady state and time resolved spectroscopic techniques together with the DNA helix melting study, we have shown that a biologically significant photosensitizer, namely, phenosafranin (PSF), can be quantitatively transferred to the DNA from the micellar nanocarrier made up of sodium tetradecyl sulfate (STS) using the external stimulant β-cyclodextrin (β-CD). The complexation property of β-CD with the nanocarrier (STS) has been utilized for the controlled release of the probe from the micelle to the DNA. Non-toxicity of the stimulant and the noninvasive nature of the carrier towards the target are expected to add to the suitability of this approach from a clinical perspective. PMID:26758082

  10. NTS-polyplex: A potential nanocarrier for neurotrophic therapy of Parkinson’s disease

    PubMed Central

    Martinez-Fong, Daniel; Bannon, Michael J.; Trudeau, Louis-Eric; Gonzalez-Barrios, Juan A.; Arango-Rodriguez, Martha L.; Hernandez-Chan, Nancy G.; Reyes-Corona, David; Armendáriz-Borunda, Juan; Navarro-Quiroga, Ivan

    2012-01-01

    Nanomedicine has focused on targeted neurotrophic gene delivery to the brain as a strategy to stop and reverse neurodegeneration in Parkinson’s disease. Because of improved transfection ability, synthetic nanocarriers have become candidates for neurotrophic therapy. Neurotensin (NTS)-polyplex is a “Trojan horse” synthetic nanocarrier system that enters dopaminergic neurons through NTS receptor internalization to deliver a genetic cargo. The success of preclinical studies with different neurotrophic genes supports the possibility of using NTS-polyplex in nanomedicine. In this review, we describe the mechanism of NTS-polyplex transfection. We discuss the concept that an effective neurotrophic therapy requires a simultaneous effect on the axon terminals and soma of the remaining dopaminergic neurons. We also discuss the future of this strategy for the treatment of Parkinson’s disease. PMID:22406187

  11. Design of novel nano-carriers for multi-enzyme co-localization

    SciTech Connect

    Jia, Feng

    2013-01-01

    The main objective of this project is to design novel nano-structured carriers and strategies to co-localize multiple enzymes to mimic the functionalities of MECs. In order to achieve this goal, distinct approaches for enzyme co-localization were developed and evaluated. Specifically, we investigated different polymeric nano-carriers, both flexible and rigid, as platforms for co-localization, as well as distinct enzyme attachment techniques using model enzyme systems using glucose oxidase and horseradish peroxidase to control the spatial arrangement of the multiple enzymes on the nanocarriers. This platform technology can be potentially used to co-localize various enzyme systems and its broad applicability will be tested using the sclareol biosynthesis process to control the formation of products through the formation of MECs with multiple enzymes NgCPS and sSsSS to regulate the pathway of reactive intermediate to enhance the final product conversion rate.

  12. Payload Drug vs. Nanocarrier Biodegradation by Myeloperoxidase- and Peroxynitrite-Mediated Oxidations: Pharmacokinetic Implications

    PubMed Central

    Seo, Wanji; Kapralov, Alexandr A.; Shurin, Galina V.; Shurin, Michael R.; Kagan, Valerian E.

    2015-01-01

    With the advancement of nanocarriers for drug delivery into biomedical practice, assessments of drug susceptibility to oxidative degradation by enzymatic mechanisms of inflammatory cells become important. Here, we investigate oxidative degradation of a carbon nanotube-based drug carrier loaded with Doxorubicin. We employed myeloperoxidase-catalysed and peroxynitrite-mediated oxidative conditions to mimic the respiratory burst of neutrophils and macrophages, respectively. In addition, we revealed that the cytostatic and cytotoxic effects of free Doxorubicin, but not nanotube-carried drug, on melanoma and lung carcinoma cell lines were abolished in the presence of tumor-activated myeloid regulatory cells that create unique myeloperoxidase- and peroxynitrite-induced oxidative conditions. Both ex vivo and in vitro studies demonstrate that the nanocarrier protects the drug against oxidative biodegradation. PMID:25902750

  13. Multifunctional metal rattle-type nanocarriers for MRI-guided photothermal cancer therapy

    NASA Astrophysics Data System (ADS)

    Huang, Yuran; Wei, Tuo; Yu, Jing; Hou, Yanglong; Cai, Kaiyong; Liang, Xing-jie

    2015-03-01

    Numerous nanomaterials have been developed for biomedical application, especially cancer therapy. Visualizing cancer therapy is highly promising now because of the potential ability to realize accurate, localized treatment. In this work, we firstly synthesized metal nanorattles (MNRs), which utilized porous gold shells capable of photothermal therapy to carry multiple superparmagnetic iron oxide nanoparticles (SPIONs) as MR imaging contrast agents inside. As shown in the infrared light, these metal rattle-typed nanostructures were able to convert to heat to kill cells, and inhibit tumor growth. As a carrier for multiple SPIONs, it also performed a good behavior for T2-weighted MR imaging in tumor site. Moreover, the rest of the inner space of the gold shell also introduced potential ability as nanocarriers for other cargos such as chemotherapeutic drugs, which is still under investigation. This metal-rattle-type nanocarriers is highly potential as a novel platforms for cancer therapy in the future.

  14. Payload drug vs. nanocarrier biodegradation by myeloperoxidase- and peroxynitrite-mediated oxidations: pharmacokinetic implications

    NASA Astrophysics Data System (ADS)

    Seo, Wanji; Kapralov, Alexandr A.; Shurin, Galina V.; Shurin, Michael R.; Kagan, Valerian E.; Star, Alexander

    2015-05-01

    With the advancement of nanocarriers for drug delivery into biomedical practice, assessments of drug susceptibility to oxidative degradation by enzymatic mechanisms of inflammatory cells become important. Here, we investigate oxidative degradation of a carbon nanotube-based drug carrier loaded with Doxorubicin. We employed myeloperoxidase-catalysed and peroxynitrite-mediated oxidative conditions to mimic the respiratory burst of neutrophils and macrophages, respectively. In addition, we revealed that the cytostatic and cytotoxic effects of free Doxorubicin, but not nanotube-carried drug, on melanoma and lung carcinoma cell lines were abolished in the presence of tumor-activated myeloid regulatory cells that create unique myeloperoxidase- and peroxynitrite-induced oxidative conditions. Both ex vivo and in vitro studies demonstrate that the nanocarrier protects the drug against oxidative biodegradation.With the advancement of nanocarriers for drug delivery into biomedical practice, assessments of drug susceptibility to oxidative degradation by enzymatic mechanisms of inflammatory cells become important. Here, we investigate oxidative degradation of a carbon nanotube-based drug carrier loaded with Doxorubicin. We employed myeloperoxidase-catalysed and peroxynitrite-mediated oxidative conditions to mimic the respiratory burst of neutrophils and macrophages, respectively. In addition, we revealed that the cytostatic and cytotoxic effects of free Doxorubicin, but not nanotube-carried drug, on melanoma and lung carcinoma cell lines were abolished in the presence of tumor-activated myeloid regulatory cells that create unique myeloperoxidase- and peroxynitrite-induced oxidative conditions. Both ex vivo and in vitro studies demonstrate that the nanocarrier protects the drug against oxidative biodegradation. Electronic supplementary information (ESI) available: Experimental details and data from characterization of materials synthesis and degradation studies. See DOI: 10

  15. Reduction-sensitive polymeric nanocarriers in cancer therapy: a comprehensive review

    NASA Astrophysics Data System (ADS)

    Deng, Bing; Ma, Ping; Xie, Yan

    2015-07-01

    Redox potential is regarded as a significant signal to distinguish between the extra-cellular and intra-cellular environments, as well as between tumor and normal tissues. Taking advantage of this physiological differentiation, various reduction-sensitive polymeric nanocarriers (RSPNs) have been designed and explored to demonstrate excellent stability during blood circulation but rapidly degrade and effectively trigger drug release in tumor cells. Therefore, this smart RSPN delivery system has attracted much attention in recent years, as it represents one of the most promising drug delivery strategies in cancer therapy. In this review, we will provide a comprehensive overview of RSPNs with various reducible linkages and functional groups up to date, including their design and synthetic strategies, preparation methods, drug release behavior, and their in vitro and in vivo efficacy in cancer therapy. In addition, dual- and triple-sensitive nanocarriers based on reducible disulfide bond-containing linkages will also be discussed.Redox potential is regarded as a significant signal to distinguish between the extra-cellular and intra-cellular environments, as well as between tumor and normal tissues. Taking advantage of this physiological differentiation, various reduction-sensitive polymeric nanocarriers (RSPNs) have been designed and explored to demonstrate excellent stability during blood circulation but rapidly degrade and effectively trigger drug release in tumor cells. Therefore, this smart RSPN delivery system has attracted much attention in recent years, as it represents one of the most promising drug delivery strategies in cancer therapy. In this review, we will provide a comprehensive overview of RSPNs with various reducible linkages and functional groups up to date, including their design and synthetic strategies, preparation methods, drug release behavior, and their in vitro and in vivo efficacy in cancer therapy. In addition, dual- and triple

  16. Current Progress in Gene Delivery Technology Based on Chemical Methods and Nano-carriers

    PubMed Central

    Jin, Lian; Zeng, Xin; Liu, Ming; Deng, Yan; He, Nongyue

    2014-01-01

    Gene transfer methods are promising in the field of gene therapy. Current methods for gene transfer include three major groups: viral, physical and chemical methods. This review mainly summarizes development of several types of chemical methods for gene transfer in vitro and in vivo by means of nano-carriers like; calcium phosphates, lipids, and cationic polymers including chitosan, polyethylenimine, polyamidoamine dendrimers, and poly(lactide-co-glycolide). This review also briefly introduces applications of these chemical methods for gene delivery. PMID:24505233

  17. Novel self-assembled pH-responsive biomimetic nanocarriers for drug delivery.

    PubMed

    Wu, Minming; Cao, Zhaoyu; Zhao, Yunfei; Zeng, Rong; Tu, Mei; Zhao, Jianhao

    2016-07-01

    Novel pH-responsive biodegradable biomimetic nanocarriers were prepared by the self-assembly of N-acetyl-l-histidine-phosphorylcholine-chitosan conjugate (NAcHis-PCCs), which was synthesized via Atherton-Todd reaction to couple biomembrane-like phosphorylcholine (PC) groups, and N,N'-carbonyldiimidazole (CDI) coupling reaction to link pH-responsive N-acetyl-l-histidine (NAcHis) moieties to chitosan. In vitro biological assay revealed that NAcHis-PCCs nanoparticles had excellent biocompatibility to avoid adverse biological response mainly owing to their biomimetic PC shell, and DLS results confirmed their pH-responsive behavior in acidic aqueous solution (pH≤6.0). Quercetin (QUE), an anti-inflammatory, antioxidant and potential anti-tumor hydrophobic drug, was effectively loaded in NAcHis-PCCs nanocarriers and showed a pH-triggered release behavior with the enhanced QUE release at acidic pH5.5 compared to neutral pH7.4. The results indicated that pH-responsive biomimetic NAcHis-PCCs nanocarriers might have great potential for site-specific delivery to pathological acidic microenvironment avoiding unfavorable biological response. PMID:27127063

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

    PubMed Central

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

    2010-01-01

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

  19. Development of a virus-mimicking nanocarrier for drug delivery systems: The bio-nanocapsule.

    PubMed

    Somiya, Masaharu; Kuroda, Shun'ichi

    2015-12-01

    As drug delivery systems, nanocarriers should be capable of executing the following functions: evasion of the host immune system, targeting to the diseased site, entering cells, escaping from endosomes, and releasing payloads into the cytoplasm. Since viruses perform some or all of these functions, they are considered naturally occurring nanocarriers. To achieve biomimicry of the hepatitis B virus (HBV), we generated the "bio-nanocapsule" (BNC)-which deploys the human hepatocyte-targeting domain, fusogenic domain, and polymerized-albumin receptor domain of HBV envelope L protein on its surface-by overexpressing the L protein in yeast cells. BNCs are capable of delivering various payloads to the cytoplasm of human hepatic cells specifically in vivo, which is achieved via formation of complexes with various materials (e.g., drugs, nucleic acids, and proteins) by electroporation, fusion with liposomes, or chemical modification. In this review, we describe BNC-related technology, discuss retargeting strategies for BNCs, and outline other virus-inspired nanocarriers. PMID:26482188

  20. Energy-Transfer Schemes To Probe Fluorescent Nanocarriers and Their Emissive Cargo.

    PubMed

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

    2015-09-01

    A strategy to probe supramolecular nanocarriers and their cargo in the intracellular space was developed on the basis of fluorescence measurements and energy transfer. It relies on the covalent attachment of an energy donor, or acceptor, to the macromolecular backbone of amphiphilic polymers and the noncovalent encapsulation of a complementary acceptor, or donor, in the resulting micelles. In aqueous environments, these macromolecules self-assemble into nanostructured constructs and bring the complementary chromophores in close proximity to enable efficient energy transfer. These supramolecular assemblies travel from the extracellular to the intracellular space and retain their integrity in the process. Indeed, donors and acceptors remain close to each other after internalization, and excitation of the former chromophores translates into significant intracellular emission from the latter. Furthermore, these supramolecular assemblies exchange their components with fast kinetics in aqueous dispersions because of the reversible character of the noncovalent contacts holding them together. As a result, micelles incorporating exclusively the donors and nanocarriers containing only the acceptors scramble their chromophoric building blocks, upon mixing, to allow the transfer of energy. These dynamic processes can be reproduced in the intracellular environment with the sequential incubation of cells with the two sets of complementary nanostructured assemblies. Thus, these operating principles and choice of supramolecular synthons are particularly valuable to monitor self-assembling nanocarriers and their cargo inside living cells and can facilitate the elucidation of the behavior of these promising delivery vehicles in a diversity of biological specimens. PMID:26275045

  1. Multifunctional Biodegradable Polyacrylamide Nanocarriers for Cancer Theranostics - A “See and Treat” Strategy

    PubMed Central

    Wang, Shouyan; Kim, Gwangseong; Lee, Yong-Eun Koo; Hah, Hoe Jin; Ethirajan, Manivannan; Pandey, Ravindra K.; Kopelman, Raoul

    2012-01-01

    We describe here the development of multifunctional nanocarriers, based on amine functionalized biodegradable polyacrylamide nanoparticles (NPs), for cancer theranostics, including active tumor targeting, fluorescence imaging and photodynamic therapy. The structural design involves adding primary amino groups and biodegradable crosslinkers during the NP polymerization, while incorporating photodynamic and fluorescent imaging agents into the NP matrix, and conjugating PEG and tumor-targeting ligands onto the surface of the NPs. The as-synthesized NPs are spherical, with an average diameter of 44 nm. An accelerated biodegradation study, using sodium hydroxide or porcine liver esterase, indicated a hydrogel polymer matrix chain collapse within several days. By using gel permeation chromatography, small molecules were detected, after the degradation. In vitro targeting studies on human breast cancer cells indicate that the targeted NPs can be transported efficiently into tumor cells. Incubating the multifunctional nanocarriers into cancer cells enabled strong fluorescence imaging. Irradiation of the photosensitizing drug, incorporated within the NPs, with light of a suitable wavelength, causes significant but selective damage to the impregnated tumor cells, but only inside the illuminated areas. Overall, the potential of polymeric-based NPs as biodegradable, multifunctional nanocarriers, for cancer theranostics, is demonstrated here. PMID:22702416

  2. Sensing protein antigen and microvesicle analytes using high-capacity biopolymer nano-carriers.

    PubMed

    Kumar, Saroj; Milani, Gloria; Takatsuki, Hideyo; Lana, Tobia; Persson, Malin; Frasson, Chiara; te Kronnie, Geertruy; Månsson, Alf

    2016-02-01

    Lab-on-a-chip systems with molecular motor driven transport of analytes attached to cytoskeletal filament shuttles (actin filaments, microtubules) circumvent challenges with nanoscale liquid transport. However, the filaments have limited cargo-carrying capacity and limitations either in transportation speed (microtubules) or control over motility direction (actin). To overcome these constraints we here report incorporation of covalently attached antibodies into self-propelled actin bundles (nanocarriers) formed by cross-linking antibody conjugated actin filaments via fascin, a natural actin-bundling protein. We demonstrate high maximum antigen binding activity and propulsion by surface adsorbed myosin motors. Analyte transport capacity is tested using both protein antigens and microvesicles, a novel class of diagnostic markers. Increased incubation concentration with protein antigen in the 0.1-100 nM range (1 min) reduces the fraction of motile bundles and their velocity but maximum transportation capacity of >1 antigen per nm of bundle length is feasible. At sub-nanomolar protein analyte concentration, motility is very well preserved opening for orders of magnitude improved limit of detection using motor driven concentration on nanoscale sensors. Microvesicle-complexing to monoclonal antibodies on the nanocarriers compromises motility but nanocarrier aggregation via microvesicles shows unique potential in label-free detection with the aggregates themselves as non-toxic reporter elements. PMID:26617251

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

    PubMed Central

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

    2013-01-01

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

  4. Glycerol monooleate-based nanocarriers for siRNA delivery in vitro.

    PubMed

    Zhen, Guoliang; Hinton, Tracey M; Muir, Benjamin W; Shi, Shuning; Tizard, Mark; McLean, Keith M; Hartley, Patrick G; Gunatillake, Pathiraja

    2012-09-01

    We present studies of the delivery of short interfering ribonucleic acid (siRNA) into a green fluorescent protein (GFP) expressing cell line, using lipid nanocarriers in cubic lyotropic liquid crystal form. These carriers are based on glycerol monooleate (GMO) and employ the use of varying concentrations of cationic siRNA binding lipids. The essential physicochemical parameters of the cationic lipid/GMO/siRNA complexes such as particle size, ζ otential, siRNA uptake stability, lyotropic mesophase behavior, cytotoxicity,and gene silencing efficiency were systematically assessed. We find that the lipid nanocarriers were effectively taken up by mammalian cells and that their siRNA payload was able to induce gene silencing in vitro. More importantly, it was found that the nonlamellar structure of some of the lipid nanocarrier formulations were more effective at gene silencing than their lamellar structured counterparts. The development of cationic lipid functionalized nonlamellar GMO-based nanostructured nanoparticles may lead to improved siRNA delivery vehicles. PMID:22794355

  5. Biopolymer nano-particles and natural nano-carriers for nano-encapsulation of phenolic compounds.

    PubMed

    Faridi Esfanjani, Afshin; Jafari, Seid Mahdi

    2016-10-01

    Phenolic compounds are major micronutrients in our diet,(1) and evidence for their role in the prevention of degenerative diseases such as cancer, inflammation and neurodegenerative diseases is emerging. The easily destruction against environment stresses and low bioavailability of phenolics are main limitations of their application. Therefore, nano-encapsulated phenolics as a fine delivery system can solve their restrictions. Polymeric nanoparticles and natural nano-carriers are one of the most effective and industrial techniques which can be used for protection and delivery of phenolics. In this review, preparation, application and characterization of polymeric based nano-capsules and natural nano-carriers for phenolics have been considered and discussed including polymeric nanoparticles, polymeric complex nanoparticles, cyclodextrins, nano-caseins, nanocrystals, electrospun nano-fibers, electro-sprayed nano-particles, and nano-spray dried particles. Our main goal was to cover the relevant recent studies in the past few years. Although a number of different types of polymeric and natural based nano-scale delivery systems have been developed, there are relatively poor quantitative understanding of their in vivo absorption, permeation and release. Also, performing toxicity experiments, residual solvent analysis and studying their biological fate during digestion, absorption, and excretion of polymeric nanoparticle and natural nano-carriers containing phenolics should be considered in future researches. In addition, future investigations could focus on application of phenolic nano-scale delivery systems in pharmaceuticals and functional foods. PMID:27419648

  6. Facile preparation of pH-responsive polyurethane nanocarrier for oral delivery.

    PubMed

    Nabid, Mohammad Reza; Omrani, Ismail

    2016-12-01

    This study reports a novel one pot synthesis of pH-responsive nanocarrier for oral delivery of hydrophobic drug under gastrointestinal tract. Triblock copolymer MPEG-HTPB-MPEG was synthesized coupling of MPEG and HTPB using hexamethylene diisocyanate(HDI) and pH-responsive carboxylic acid group was attached to polybuthadiene backbone by thiol-ene click reaction in a facile and convenient procedure. The MPEG-HTPB (g-COOH)-MPEG block copolymers were self-organized into micelle assemblies in the water. The size and shape of the micelle assemblies were confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The nanocarriers have high drug loading ability for poorly water-soluble drug. The pH-responsive profile was demonstrated by pH-dependent swelling and in vitro drug release. <10.0% IBU was released under artificial gastric fluid after 2h, whereas an immediate release was observed under artificial intestinal fluid. The XTT assay indicated that the micelle obtained from PEG-HTPB (g-COOH)-PEG triblock copolymer are safe in a wide range of concentrations. The results show that pH-responsive PEG-HTPB (g-COOH)-PEG triblock copolymers are promising nanocarriers for the oral administration of hydrophobic drugs. PMID:27612744

  7. Nanocarriers for photodynamic therapy-rational formulation design and medium-scale manufacture.

    PubMed

    Villa Nova, Mônica; Janas, Christine; Schmidt, Mike; Ulshoefer, Thomas; Gräfe, Susanna; Schiffmann, Susanne; de Bruin, Natasja; Wiehe, Arno; Albrecht, Volker; Parnham, Michael J; Luciano Bruschi, Marcos; Wacker, Matthias G

    2015-08-01

    The development and manufacture of novel nanocarriers for drug delivery has proved challenging with regards to scale-up and pharmaceutical quality. Polymeric nanocarriers composed of poly(lactic-co-glycolic acid)-b-poly(ethylene glycol) (PLGA-PEG) were prepared and the photosensitizer meso-tetrakis(3-hydroxyphenyl) chlorin (mTHPC) was effectively encapsulated. Furthermore, the interplay of various process and formulation parameters and their impact on the most important product specifications were investigated by using a factorial design and a central composite design in a microfluidic manufacturing process. These nanoparticles for intravenous administration with a size of 97 ± 0.13 nm, narrow size distribution, and an encapsulation efficiency of more than 80% were produced at high throughput. In vitro stability and in vitro drug release testing were applied for quality control purposes. Finally, the toxicity of the photosensitizer was tested in vitro. The cytotoxicity was successfully reduced while the efficacy of the formulation was maintained. First observations using in vivo imaging suggest effective distribution of the nanocarrier system after injection into rodents. Thus, further in vivo testing of the beneficial effects of nanoencapsulation into the matrix system and its formulation will be considered for the delivery of mTHPC to tumor tissues during photodynamic therapy. PMID:26123822

  8. Rice bran and raspberry seed oil-based nanocarriers with self-antioxidative properties as safe photoprotective formulations.

    PubMed

    Niculae, Gabriela; Lacatusu, Ioana; Badea, Nicoleta; Stan, Raluca; Vasile, Bogdan Stefan; Meghea, Aurelia

    2014-04-01

    The aim of this research was to develop advanced lipid nanocarriers based on renewable vegetable resources (rice bran oil and raspberry seed oil) that possess self-antioxidative properties, having advantages in terms of minimal side effects and exhibiting the ability to simultaneously co-encapsulate and co-release two active compounds. The focus has been oriented towards developing safe cosmetic formulations with broad-spectrum photoprotection based on these new lipid nanocarriers that contain large amounts of vegetable oils and low concentrations of synthetic UVA and UVB filters (butyl-methoxydibenzoylmethane - BMDBM and octocrylene - OCT). The lipid nanocarriers have a spherical shape and show good physical stability, with a zeta potential in the range of -25.5 to -32.4 mV. Both vegetable oils play a key role in the preparation of efficient nanocarriers, leading to a less ordered arrangement of the lipid core that offers many spaces for the entrapment of large amounts of BMDBM (79%) and OCT (90%), as wells as improved antioxidant activity and UV absorption properties, particularly for the lipid nanocarriers prepared from rice bran oil. By formulating the lipid nanocarriers into creams containing only 3.5% of the UV filters and 10.5% of the vegetable oils, the resulting sunscreens exhibited improved photoprotection, reflecting up to 91% and 93% of UVA and UVB rays, respectively. A new direction of research achieved by this study is the multiple release strategy of both UV filters from the same lipid nanocarrier. After 24 hours, a slow release of BMDBM (less than 4%) and OCT (17.5%) was obtained through a Fick diffusion process. This study demonstrates a significant advance in the areas of both nanotechnology and cosmetics, developing safer cosmetic formulations that possess broad antioxidant, photoprotective and co-release effectiveness due to the existence of a high content of nanostructured vegetable oils combined with a low amount of synthetic UV filters in the

  9. Nanocarrier-mediated inhibition of macrophage migration inhibitory factor attenuates secondary injury after spinal cord injury.

    PubMed

    Saxena, Tarun; Loomis, Kristin H; Pai, S Balakrishna; Karumbaiah, Lohitash; Gaupp, Eric; Patil, Ketki; Patkar, Radhika; Bellamkonda, Ravi V

    2015-02-24

    Spinal cord injury (SCI) can lead to permanent motor and sensory deficits. Following the initial traumatic insult, secondary injury mechanisms characterized by persistent heightened inflammation are initiated and lead to continued and pervasive cell death and tissue damage. Anti-inflammatory drugs such as methylprednisolone (MP) used clinically have ambiguous benefits with debilitating side effects. Typically, these drugs are administered systemically at high doses, resulting in toxicity and paradoxically increased inflammation. Furthermore, these drugs have a small time window postinjury (few hours) during which they need to be infused to be effective. As an alternative to MP, we investigated the effect of a small molecule inhibitor (Chicago sky blue, CSB) of macrophage migration inhibitory factor (MIF) for treating SCI. The pleiotropic cytokine MIF is known to contribute to upregulation of several pro-inflammatory cytokines in various disease and injury states. In vitro, CSB administration alleviated endotoxin-mediated inflammation in primary microglia and macrophages. Nanocarriers such as liposomes can potentially alleviate systemic side effects of high-dose therapy by enabling site-specific drug delivery to the spinal cord. However, the therapeutic window of 100 nm scale nanoparticle localization to the spinal cord after contusion injury is not fully known. Thus, we first investigated the ability of nanocarriers of different sizes to localize to the injured spinal cord up to 2 weeks postinjury. Results from the study showed that nanocarriers as large as 200 nm in diameter could extravasate into the injured spinal cord up to 96 h postinjury. We then formulated nanocarriers (liposomes) encapsulating CSB and administered them intravenously 48 h postinjury, within the previously determined 96 h therapeutic window. In vivo, in this clinically relevant contusion injury model in rats, CSB administration led to preservation of vascular and white matter integrity

  10. Synthesis and Characterization of a Poly(amido amine) Modified Magnetic Nanocarrier for Controlled Delivery of Doxorubicin.

    PubMed

    Xu, Shanshan; Wu, Juan; Jiang, Wei; Tian, Renbing

    2016-02-01

    We prepared a magnetic poly(amido amine) (G2.5)-hydrazine hydrate nanocarrier, denoted by MNPs@PAMAM-H. PAMAM dendrimer was conjugated onto the surface of magnetic nanoparticles (MNPs) to increase the biocompatibility of the nanocarrier and provided a large number of reactive sites for coupling of drug molecules. DOX was covalently attached to the nanocarrier via a pH-sensitive linker, hydrazone bond, which hydrolyzes in the acidic lysosomal environment to allow pH-sensitive release of DOX. DOX was successfully loaded into the nanocarrier with a high drug loading (27.53%) and entrapment efficiency (86.44%). Nearly 88% DOX was released within 60 h at pH 5.0, compared with only 30% at pH 7.4. The in vitro MTT assay in HeLa cells demonstrated that MNPs@PAMAM-DOX exhibited high anti-tumor activity, while the MNPs@PAMAM-H were practically non-toxic. These results revealed that MNPs@ PAMAM-H were biocompatible. The Synthesized nanocarrier had the potential to be used as MR probe and guide DOX to enter target sites in cancer therapy by an outer magnet. PMID:27433587

  11. Liposomal Systems as Nanocarriers for the Antiviral Agent Ivermectin.

    PubMed

    Croci, Romina; Bottaro, Elisabetta; Chan, Kitti Wing Ki; Watanabe, Satoru; Pezzullo, Margherita; Mastrangelo, Eloise; Nastruzzi, Claudio

    2016-01-01

    RNA virus infections can lead to the onset of severe diseases such as fever with haemorrhage, multiorgan failure, and mortality. The emergence and reemergence of RNA viruses continue to pose a significant public health threat worldwide with particular attention to the increasing incidence of flaviviruses, among others Dengue, West Nile Virus, and Yellow Fever viruses. Development of new and potent antivirals is thus urgently needed. Ivermectin, an already known antihelminthic drug, has shown potent effects in vitro on Flavivirus helicase, with EC50 values in the subnanomolar range for Yellow Fever and submicromolar EC50 for Dengue Fever, Japanese encephalitis, and tick-borne encephalitis viruses. However ivermectin is hampered in its application by pharmacokinetic problems (little solubility and high cytotoxicity). To overcome such problems we engineered different compositions of liposomes as ivermectin carriers characterizing and testing them on several cell lines for cytotoxicity. The engineered liposomes were less cytotoxic than ivermectin alone and they showed a significant increase of the antiviral activity in all the Dengue stains tested (1, 2, and S221). In the current study ivermectin is confirmed to be an effective potential antiviral and liposomes, as drug carriers, are shown to modulate the drug activity. All together the results represent a promising starting point for future improvement of ivermectin as antiviral and its delivery. PMID:27242902

  12. Liposomal Systems as Nanocarriers for the Antiviral Agent Ivermectin

    PubMed Central

    Croci, Romina; Bottaro, Elisabetta; Chan, Kitti Wing Ki; Watanabe, Satoru; Pezzullo, Margherita; Mastrangelo, Eloise; Nastruzzi, Claudio

    2016-01-01

    RNA virus infections can lead to the onset of severe diseases such as fever with haemorrhage, multiorgan failure, and mortality. The emergence and reemergence of RNA viruses continue to pose a significant public health threat worldwide with particular attention to the increasing incidence of flaviviruses, among others Dengue, West Nile Virus, and Yellow Fever viruses. Development of new and potent antivirals is thus urgently needed. Ivermectin, an already known antihelminthic drug, has shown potent effects in vitro on Flavivirus helicase, with EC50 values in the subnanomolar range for Yellow Fever and submicromolar EC50 for Dengue Fever, Japanese encephalitis, and tick-borne encephalitis viruses. However ivermectin is hampered in its application by pharmacokinetic problems (little solubility and high cytotoxicity). To overcome such problems we engineered different compositions of liposomes as ivermectin carriers characterizing and testing them on several cell lines for cytotoxicity. The engineered liposomes were less cytotoxic than ivermectin alone and they showed a significant increase of the antiviral activity in all the Dengue stains tested (1, 2, and S221). In the current study ivermectin is confirmed to be an effective potential antiviral and liposomes, as drug carriers, are shown to modulate the drug activity. All together the results represent a promising starting point for future improvement of ivermectin as antiviral and its delivery. PMID:27242902

  13. EGF receptor-targeted nanocarriers for enhanced cancer treatment.

    PubMed

    Master, Alyssa M; Sen Gupta, Anirban

    2012-12-01

    The 'nanomedicine' approach has revolutionized cancer therapy by enabling the packaging of therapeutic agents within engineered nanovehicles that can specifically accumulate within the tumor stroma and then be internalized within cancer cells, to render site-selective action while minimizing nonspecific uptake and harmful side effects. While the specific accumulation within the tumor stroma is rendered by the ability of the nanovehicles to passively permeate through the tumor's leaky vasculature, the cellular internalization is often achieved by exploiting receptor-mediated active endocytotic mechanisms using receptor-specific ligand decoration on the vehicle surface. To this end, a highly important receptor found in several cancers is the EGF receptor, which has been implicated in tumor aggression and proliferation. In this context, we provide a comprehensive review of the various approaches of ligand decorations on nanovehicles for active targeting to EGF receptors, and discuss their pros and cons towards optimizing the design of EGF receptor-targeted nanomedicine systems. PMID:23249333

  14. The acceptability of nanocarriers for drug delivery in different contexts of use: perceptions of researchers and research trainees in the field of new technologies

    PubMed Central

    Chenel, Vanessa; Boissy, Patrick; Poirier, Marie-Sol; Cloarec, Jean-Pierre; Patenaude, Johane

    2015-01-01

    Background Despite marked optimism in the field of nanomedicine about the use of drug-delivery nanocarriers, uncertainties exist concerning nanocarriers’ possible unintended impacts and effects. These uncertainties could affect user acceptance and acceptability. “Acceptance” refers to the intention to put a technology or a device to a specified use. “Acceptability” refers to a value judgment that accounts for acceptance. The objectives of this study were to characterize impact perception, acceptance, and acceptability in relation to drug-delivery nanocarriers in different contexts of use, and to explore relationships among these concepts. Methods A sample of European and Canadian researchers and graduate research trainees active in the field of new technologies was recruited by targeted email invitation for participation in a web-based questionnaire study. The questionnaire presented scenarios for two contexts of use (lung cancer, seasonal flu) of drug-delivery nanocarriers with two compositions (carbon, synthetic DNA). Respondents’ impact perception, acceptance, and acceptability judgment in relation to each kind of nanocarrier in each context of use were measured with Likert scale questions and scored using categorical values. Results Two hundred and fourteen researchers and graduate research trainees completed the questionnaire. The results showed that nanocarrier composition influenced impact perception: as compared with the carbon nanocarrier impact perception, the positive impacts of the synthetic DNA nanocarrier were perceived as more significant and more likely to occur than its negative impacts. Composition did not influence acceptance or acceptability. Context of use significantly influenced acceptance and acceptability of both kinds of nanocarriers: researchers were more likely to accept the use of nanocarriers to treat lung cancer than the seasonal flu. The results also showed a significant relationship between acceptance and the perceived

  15. Construction of Fe3O4/Vancomycin/PEG Magnetic Nanocarrier for Highly Efficient Pathogen Enrichment and Gene Sensing.

    PubMed

    Zhu, Minjun; Liu, Weipeng; Liu, Hongxing; Liao, Yuhui; Wei, Jitao; Zhou, Xiaoming; Xing, Da

    2015-06-17

    Infectious diseases, especially pathogenic bacterial infections, pose a growing threat to public health worldwide. As pathogenic bacteria usually exist in complex experimental matrixes at very low concentrations, developing a technology for rapid and biocompatible sample enrichment is essential for sensitive diagnosis. In this study, an Fe3O4/Vancomycin/PEG magnetic nanocarrier was constructed for efficient sample enrichment and in situ nucleic acid preparation of pathogenic bacteria for subsequent gene sensing. We attached Vancomycin, a well-known broad-spectrum antibiotic, to the surface of Fe3O4 nanoparticles as a universal molecular probe to target bacterial cells. Polyethylene glycol (PEG) was introduced to enhance the nanocarrier's water solubility and biocompatibility. Results show that the proposed nanocarrier achieved a 90% capture efficiency even if at a Listeria monocytogenes concentration of 1×10(2) cfu/mL. Contributing to the good water solubility achieved by the employment of modified PEG, highly efficient enrichment (enrichment factor 10 times higher than PEG-free nanocarrier) can be completed in 30 min. Moreover, PEG would also develop the nanoparticles' biocompatibility by passivating the positively charged unreacted amines on the magnetic nanoparticles, thus helping to release the negatively charged bacterial genome from the nanocarrier/bacteria complexes when an in situ nucleic acids extraction step was executed. The outstanding bacterial capture capability and biocompatibility of this nanocarrier enabled the implementation of a highly sensitive gene-sensing strategy of pathogens. By employing an electrochemiluminescence-based gene-sensing assay, L. monocytogenes can be rapidly detected with a limit of detection of 10 cfu/mL, which shows great potential for clinical applications. PMID:26005899

  16. Preparation of a multifunctional verapamil-loaded nano-carrier based on a self-assembling PEGylated prodrug.

    PubMed

    Zhao, Dongping; Liu, Na; Shi, Kemei; Wang, Xiaojuan; Wu, Guolin

    2015-11-01

    In an effort to prove the inherent side effects of doxorubicin (DOX) and potentially revoke the effects of drug resistance exhibited by cancer cells, we have designed a multifunctional DOX-delivery nano-carrier system able to encapsulate the drug resistance reversal agent Verapamil HCl (VRP·HCl). Hydrophilic short-chain polyethylene glycol (i.e., mPEG) was covalently linked to hydrophobic DOX and a benzoic imine linkage was used to form a linear amphiphilic PEGylated prodrug, namely mPEG-b-DOX. In aqueous solution, the amphiphilic PEG-b-DOX is able to self-assemble to form stable nanoparticles with a DOX loading content of approximately 40 wt% and a diameter of ∼ 143 nm. The resulting nanoparticles can simultaneously serve as an anticancer drug conjugate and as a drug carrier system. Here, the hydrophilic VRP could be encapsulated into the nano-carriers via a conventional dialysis method. The loading efficiency in mPEG-b-DOX nano-carrier was determined to be 53.97% and the loading content was found to be 7.71 wt%. The VRP-loaded nano-carriers grew slightly in size, to a diameter of ∼ 177 nm. We found that the release of DOX and VRP was much faster at a lower pH value. The biological activity of the nano-carriers were evaluated in vitro and compared with the DOX-loaded system. In doing so we found that the VRP-loaded nano-carrier features a much higher antitumor activity. Furthermore, the combined-system exhibits a significantly enhanced cytotoxicity with an elevated apoptosis rate observed for MCF-7/ADR used as a cell line in this in vitro study. This combinatory system and promising candidate for applications involving DOX chemotherapy proved to be easy to prepare and could be characterized in terms of biocompatibility, biodegradability, loading capacity, pH responsiveness and reversal of drug resistance. PMID:26340357

  17. Development of oxaliplatin encapsulated in magnetic nanocarriers of pectin as a potential targeted drug delivery for cancer therapy

    PubMed Central

    Dutta, Raj Kumar; Sahu, Saurabh

    2012-01-01

    Superparamagnetic iron oxide nanoparticles (SPIONs) and oxaliplatin (OHP) were in-situ encapsulated in pectin cross-linked with Ca2+ forming 100–200 nm sized magnetically functionalized pectin nanocarriers, referred here as MP-OHP nanocarriers. The scanning electron microscopy (SEM) and transmission electron microscopy (TEM) studies revealed formation of spherical nanostructures. The magnetic measurements by vibration sample magnetometer (VSM) revealed high saturation magnetization (Ms=45.65 emu/g). The superparamagnetic property of MP-OHP was confirmed from the blocking temperature (TB) determined from field cooled and zero field cooled magnetization, measured by superconducting quantum unit interference device (SQUID) magnetometry. The stability of the aqueous dispersion of MP-OHP nanocarriers was confirmed from its high zeta potential (−30.5 mV). The drug encapsulation efficiency (55.2±4.8% w/w) and the drug loading content (0.10±0.04 wt%) in MP-OHP nanocarriers were determined from corresponding platinum contents in OHP and MP-OHP batches measured by inductively coupled plasma mass spectrometry (ICPMS). These nanocarriers exhibited a sustained release of OHP in phosphate buffer solution maintained at pH 5.5 and 7.4, where the drug release profile satisfied a combination of diffusion and swelling controlled mechanism. The cytotoxicity effect of MP-OHP nanocarriers was studied on MIA-PaCa-2 (pancreas) cancer cell line, where the GI50 values were more than 5 mg/mL and it exhibited 10 folds higher cytoxicity than the equivalent concentration of free drug. PMID:25755993

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

    PubMed Central

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

    2008-01-01

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

  19. The Use ofa Hydrophobic Binding Peptide Modified Lipid Nanocarrier Improving Tumor Distribution and Antitumor Efficacy.

    PubMed

    Gao, Wei; Yang, Xiucong; Lin, Zhiqiang; Gao, Shanyun; He, Bing; Mei, Bong; Wang, Dan; Yuan, Lan; Zhang, Hua; Dai, Wenbing; Wang, Xueqing; Wang, Jiancheng; Zhang, Xuan; Zhang, Qiang

    2016-06-01

    In addition to showing the specific interaction between a generalized ligand and its receptor and the electrostatic effect between positive cell-penetrating peptides and negative cell membranes, our last study demonstrated the hydrophobic interactivity between a hydrophobic binding peptide (HBP) and biomembranes to be favorable in drug delivery. To yield more evidence for this new strategy and to find more effective HBPs, here we designed and established a novel nanomedicine associated with cyclosporin A (CsA) because this peptide is electrically neutral, highly hydrophobic, very stable in vivo and safe at the given dose. First, isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR) studies showed a strong hydrophobic interaction between the CsA molecules and the lipid membrane. The lactate dehydrogenase release assay proved that CsA exhibited low toxicity to cell membranes. These facts encouraged us to explore the potential application of CsA as an HBP to actualize intracellular delivery of nanomedicines for tumor therapy. When conjugated to lipid nanocarriers, CsA significantly enhanced their binding with cells and,. consequently, increased the internalization of recoded nanomedicines into cells. The in vivo experiments further showed that the CsA-associated nanocarriers could achieve better delivery to tumor tissues and improve the tumor therapy of doxorubicin (DOX) compared to the nonmodified control; these findings were identical to the observations-in cell studies. In conclusion, CsA, a readily obtainable molecule with favorable characteristics, is indeed a good candidate for an HBP, and this study provides solid, novel evidence for the use of HBP-based nanocarriers as effective antitumor drug delivery systems. PMID:27319213

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

    PubMed

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

    2016-04-10

    Glioblastoma multiforme, a grade IV glioma, is the most frequently occurring and invasive primary tumor of the central nervous system, which causes about 4% of cancer-associated-deaths, making it one of the most fatal cancers. With present treatments, using state-of-the-art technologies, the median survival is about 14months and 2year survival rate is merely 3-5%. Hence, novel therapeutic approaches are urgently necessary. However, most drug molecules are not able to cross the blood-brain barrier, which is one of the major difficulties in glioblastoma treatment. This review describes the features of blood-brain barrier, and its anatomical changes with different stages of tumor growth. Moreover, various strategies to improve brain drug delivery i.e. tight junction opening, chemical modification of the drug, efflux transporter inhibition, convection-enhanced delivery, craniotomy-based drug delivery and drug delivery nanosystems are discussed. Nanocarriers are one of the highly potential drug transport systems that have gained huge research focus over the last few decades for site specific drug delivery, including drug delivery to the brain. Properly designed nanocolloids are capable to cross the blood-brain barrier and specifically deliver the drug in the brain tumor tissue. They can carry both hydrophilic and hydrophobic drugs, protect them from degradation, release the drug for sustained period, significantly improve the plasma circulation half-life and reduce toxic effects. Among various nanocarriers, liposomes, polymeric nanoparticles and lipid nanocapsules are the most widely studied, and are discussed in this review. For each type of nanocarrier, a general discussion describing their composition, characteristics, types and various uses is followed by their specific application to glioblastoma treatment. Moreover, some of the main challenges regarding toxicity and standardized evaluation techniques are narrated in brief. PMID:26892752

  1. Nanocarriers for intravenous injection--the long hard road to the market.

    PubMed

    Wacker, Matthias

    2013-11-30

    Nanodispersed drug delivery systems for the intravenous injection have successfully overcome the hurdle of drug approval in the European Union and the United States. Although there is a need for highly advanced nanocarrier devices they have not been the result of a rational formulation design but were developed as stand-alone products in a long chain of case-by-case studies. This review focuses on aspects in development, composition, and manufacture of these innovative dosage forms that are relevant for the translation into new drug products. PMID:24036012

  2. Formulation Development and Evaluation of Hybrid Nanocarrier for Cancer Therapy: Taguchi Orthogonal Array Based Design

    PubMed Central

    Tekade, Rakesh K.; Chougule, Mahavir B.

    2013-01-01

    Taguchi orthogonal array design is a statistical approach that helps to overcome limitations associated with time consuming full factorial experimental design. In this study, the Taguchi orthogonal array design was applied to establish the optimum conditions for bovine serum albumin (BSA) nanocarrier (ANC) preparation. Taguchi method with L9 type of robust orthogonal array design was adopted to optimize the experimental conditions. Three key dependent factors namely, BSA concentration (% w/v), volume of BSA solution to total ethanol ratio (v : v), and concentration of diluted ethanolic aqueous solution (% v/v), were studied at three levels 3%, 4%, and 5% w/v; 1 : 0.75, 1 : 0.90, and 1 : 1.05 v/v; 40%, 70%, and 100% v/v, respectively. The ethanolic aqueous solution was used to impart less harsh condition for desolvation and attain controlled nanoparticle formation. The interaction plot studies inferred the ethanolic aqueous solution concentration to be the most influential parameter that affects the particle size of nanoformulation. This method (BSA, 4% w/v; volume of BSA solution to total ethanol ratio, 1 : 0.90 v/v; concentration of diluted ethanolic solution, 70% v/v) was able to successfully develop Gemcitabine (G) loaded modified albumin nanocarrier (M-ANC-G) of size 25.07 ± 2.81 nm (ζ = −23.03 ± 1.015 mV) as against to 78.01 ± 4.99 nm (ζ = −24.88 ± 1.37 mV) using conventional method albumin nanocarrier (C-ANC-G). Hybrid nanocarriers were generated by chitosan layering (solvent gelation technique) of respective ANC to form C-HNC-G and M-HNC-G of sizes 125.29 ± 5.62 nm (ζ = 12.01 ± 0.51 mV) and 46.28 ± 2.21 nm (ζ = 15.05 ± 0.39 mV), respectively. Zeta potential, entrapment, in vitro release, and pH-based stability studies were investigated and influence of formulation parameters are discussed. Cell-line-based cytotoxicity assay (A549 and H460 cells) and cell internalization assay (H460 cell line) were

  3. Phage display: development of nanocarriers for targeted drug delivery to the brain

    PubMed Central

    Bakhshinejad, Babak; Karimi, Marzieh; Khalaj-Kondori, Mohammad

    2015-01-01

    The blood brain barrier represents a formidable obstacle for the transport of most systematically administered neurodiagnostics and neurotherapeutics to the brain. Phage display is a high throughput screening strategy that can be used for the construction of nanomaterial peptide libraries. These libraries can be screened for finding brain targeting peptide ligands. Surface functionalization of a variety of nanocarriers with these brain homing peptides is a sophisticated way to develop nanobiotechnology-based drug delivery platforms that are able to cross the blood brain barrier. These efficient drug delivery systems raise our hopes for the diagnosis and treatment of various brain disorders in the future. PMID:26199590

  4. EGF receptor-targeted nanocarriers for enhanced cancer treatment

    PubMed Central

    Master, Alyssa M; Gupta, Anirban Sen

    2013-01-01

    The ‘nanomedicine’ approach has revolutionized cancer therapy by enabling the packaging of therapeutic agents within engineered nanovehicles that can specifically accumulate within the tumor stroma and then be internalized within cancer cells, to render site-selective action while minimizing nonspecific uptake and harmful side effects. While the specific accumulation within the tumor stroma is rendered by the ability of the nanovehicles to passively permeate through the tumor’s leaky vasculature, the cellular internalization is often achieved by exploiting receptor-mediated active endocytotic mechanisms using receptor-specific ligand decoration on the vehicle surface. To this end, a highly important receptor found in several cancers is the EGF receptor, which has been implicated in tumor aggression and proliferation. In this context, we provide a comprehensive review of the various approaches of ligand decorations on nanovehicles for active targeting to EGF receptors, and discuss their pros and cons towards optimizing the design of EGF receptor-targeted nanomedicine systems. PMID:23249333

  5. Self-Assembled Smart Nanocarriers for Targeted Drug Delivery.

    PubMed

    Cui, Wei; Li, Junbai; Decher, Gero

    2016-02-01

    Nanostructured drug-carrier systems promise numerous benefits for drug delivery. They can be engineered to precisely control drug-release rates or to target specific sites within the body with a specific amount of therapeutic agent. However, to achieve the best therapeutic effects, the systems should be designed for carrying the optimum amount of a drug to the desired target where it should be released at the optimum rate for a specified time. Despite numerous attempts, fulfilling all of these requirements in a synergistic way remains a huge challenge. The trend in drug delivery is consequently directed toward integrated multifunctional carrier systems, providing selective recognition in combination with sustained or triggered release. Capsules as vesicular systems enable drugs to be confined for controlled release. Furthermore, carriers modified with recognition groups can enhance the capability of encapsulated drug efficacy. Here, recent advances are reviewed regarding designing and preparing assembled capsules with targeting ligands or size controllable for selective recognition in drug delivery. PMID:26436442

  6. Protection of bronze artefacts through polymeric coatings based on nanocarriers filled with corrosion inhibitors

    NASA Astrophysics Data System (ADS)

    de Luna, Martina Salzano; Buonocore, Giovanna; Di Carlo, Gabriella; Giuliani, Chiara; Ingo, Gabriel M.; Lavorgna, Marino

    2016-05-01

    Protective coatings based on polymers synthesized from renewable sources (chitosan or an amorphous vinyl alcohol based polymer) have been prepared for the protection of bronze artifacts from corrosion. Besides acting as an effective barrier against corrosive species present in the environment, the efficiency of the coatings has been improved by adding corrosion inhibitor compounds (benzotriazole or mercaptobenzothiazole) to the formulations. The liquid medium of the formulations has been carefully selected looking at maximizing the wettability on the bronze substrate and optimizing the solvent evaporation rate. The minimum amount of inhibitor compounds has been optimized by performing accelerated corrosion tests on coated bronze substrates. The inhibitors have been directly dissolved in the coating-forming solutions and/or introduced by means of nanocarriers, which allow to control the release kinetics. The free dissolved inhibitor molecules immediately provide a sufficient protection against corrosion. On the other hand, the inhibitor molecules contained in the nanocarriers serve as long-term reservoir, which can be activated by external corrosion-related stimuli in case of particularly severe conditions. Particular attention has been paid to other features which affect the coating performances. Specifically, the adhesion of the protective polymer layer to the bronze substrate has been assessed, as well as its permeability properties and transparency, the latter being a fundamental feature of protective coating for cultural heritages. Finally, the protective efficiency of the produced smart coatings has been assessed through accelerated corrosion tests.

  7. Charge-selective fractions of naturally occurring nanoparticles as bioactive nanocarriers for cancer therapy.

    PubMed

    Wang, Yongzhong; Yi, Sijia; Sun, Leming; Huang, Yujian; Zhang, Mingjun

    2014-10-01

    A carnivorous fungus, Arthrobotrys oligospora, has been shown to secrete nanoparticles. In the present work, the potential of two charge-selective fractions of fungal nanoparticles (FNPs) as bioactive nanocarriers in cancer therapy is explored by investigating their immunostimulatory activities, cytotoxic mechanisms and in vitro immunochemotherapeutic effects. A surface charge-selective fractionation procedure to purify crude FNPs has been established, and two FNP fractions (i.e. FNP1 and FNP2), with different surface charges and similarly reduced diameters of 100-200nm, are obtained. Both FNP fractions enhance the secretion of multiple proinflammatory cytokines and chemokines from macrophages and splenocytes. However, FNP2 has stronger cytotoxicity than FNP1. It is FNP2 not FNP1 that could clearly inhibit cell proliferation by inducing apoptosis and arresting cells at the sub G0/G1 phase. Both the FNP fractions can form pH-responsive nanocomplexes with doxorubicin (DOX) via electrostatic interactions. For direct cytotoxicity, DOX-FNP2 complexes demonstrate higher activity than DOX against multiple tumor cells, while DOX-FNP1 complexes show weaker activity than DOX. Interestingly, in a co-culture experiment where splenocytes are co-cultured with tumor cells, both DOX-FNP complexes demonstrate higher cytotoxicity than DOX. In conclusion, this work proposes a combined therapeutics for cancer treatment using charge-selective fractions of FNPs as bioactive nanocarriers. PMID:24952072

  8. Preparation and evaluation of novel mixed micelles as nanocarriers for intravenous delivery of propofol.

    PubMed

    Li, Xinru; Zhang, Yanhui; Fan, Yating; Zhou, Yanxia; Wang, Xiaoning; Fan, Chao; Liu, Yan; Zhang, Qiang

    2011-01-01

    Novel mixed polymeric micelles formed from biocompatible polymers, poly(ethylene glycol)-poly(lactide) (mPEG-PLA) and polyoxyethylene-660-12-hydroxy stearate (Solutol HS15), were fabricated and used as a nanocarrier for solubilizing poorly soluble anesthetic drug propofol. The solubilization of propofol by the mixed micelles was more efficient than those made of mPEG-PLA alone. Micelles with the optimized composition of mPEG-PLA/Solutol HS15/propofol = 10/1/5 by weight had particle size of about 101 nm with narrow distribution (polydispersity index of about 0.12). Stability analysis of the mixed micelles in bovine serum albumin (BSA) solution indicated that the diblock copolymer mPEG efficiently protected the BSA adsorption on the mixed micelles because the hydrophobic groups of the copolymer were efficiently screened by mPEG, and propofol-loaded mixed micelles were stable upon storage for at least 6 months. The content of free propofol in the aqueous phase for mixed micelles was lower by 74% than that for the commercial lipid emulsion. No significant differences in times to unconsciousness and recovery of righting reflex were observed between mixed micelles and commercial lipid formulation. The pharmacological effect may serve as pharmaceutical nanocarriers with improved solubilization capacity for poorly soluble drugs. PMID:21711808

  9. Triolein-based polycation lipid nanocarrier for efficient gene delivery: characteristics and mechanism.

    PubMed

    Zhang, Zhiwen; Fang, Xiaoling; Hao, Junguo; Li, Yajuan; Sha, Xianyi

    2011-01-01

    We proposed to develop a polycation lipid nanocarrier (PLN) with higher transfection efficiency than our previously described polycation nanostrucutred lipid nanocarrier (PNLC). PLN was composed of triolein, cetylated low-molecular-weight polyethylenimine, and dioleoyl phosphatidylethanolamine. The physicochemical properties of PLN and the PLN/DNA complexes (PDC) were characterized. The in vitro transfection was performed in human lung adenocarcinoma (SPC-A1) cells, and the intracellular mechanism was investigated as well. The measurements indicated that PLN and PDC are homogenous nanometer-sized particles with a positive charge. The transfection efficiency of PDC significantly increased with the content of triolein and was higher than that of PNLC and commercial Lipofectamine 2000. In particular, the transfection of PLN in the presence of 10% serum was more effective than that in its absence. With the help of specific inhibitors of chlorpromazine and filipin, the clathrin-dependent endocytosis pathway was determined to be the main contributor to the successful transfection mediated by PLN in SPC-A1 cells. The captured images verified that the fluorescent PDC was localized in the lysosomes and nuclei after endocytosis. Thus, PLN represents a novel efficient nonviral gene delivery vector. PMID:22114487

  10. Preparation and evaluation of novel mixed micelles as nanocarriers for intravenous delivery of propofol

    NASA Astrophysics Data System (ADS)

    Li, Xinru; Zhang, Yanhui; Fan, Yating; Zhou, Yanxia; Wang, Xiaoning; Fan, Chao; Liu, Yan; Zhang, Qiang

    2011-12-01

    Novel mixed polymeric micelles formed from biocompatible polymers, poly(ethylene glycol)-poly(lactide) (mPEG-PLA) and polyoxyethylene-660-12-hydroxy stearate (Solutol HS15), were fabricated and used as a nanocarrier for solubilizing poorly soluble anesthetic drug propofol. The solubilization of propofol by the mixed micelles was more efficient than those made of mPEG-PLA alone. Micelles with the optimized composition of mPEG-PLA/Solutol HS15/propofol = 10/1/5 by weight had particle size of about 101 nm with narrow distribution (polydispersity index of about 0.12). Stability analysis of the mixed micelles in bovine serum albumin (BSA) solution indicated that the diblock copolymer mPEG efficiently protected the BSA adsorption on the mixed micelles because the hydrophobic groups of the copolymer were efficiently screened by mPEG, and propofol-loaded mixed micelles were stable upon storage for at least 6 months. The content of free propofol in the aqueous phase for mixed micelles was lower by 74% than that for the commercial lipid emulsion. No significant differences in times to unconsciousness and recovery of righting reflex were observed between mixed micelles and commercial lipid formulation. The pharmacological effect may serve as pharmaceutical nanocarriers with improved solubilization capacity for poorly soluble drugs.

  11. Vascular Targeting of Nanocarriers: Perplexing Aspects of the Seemingly Straightforward Paradigm

    PubMed Central

    2015-01-01

    Targeted nanomedicine holds promise to find clinical use in many medical areas. Endothelial cells that line the luminal surface of blood vessels represent a key target for treatment of inflammation, ischemia, thrombosis, stroke, and other neurological, cardiovascular, pulmonary, and oncological conditions. In other cases, the endothelium is a barrier for tissue penetration or a victim of adverse effects. Several endothelial surface markers including peptidases (e.g., ACE, APP, and APN) and adhesion molecules (e.g., ICAM-1 and PECAM) have been identified as key targets. Binding of nanocarriers to these molecules enables drug targeting and subsequent penetration into or across the endothelium, offering therapeutic effects that are unattainable by their nontargeted counterparts. We analyze diverse aspects of endothelial nanomedicine including (i) circulation and targeting of carriers with diverse geometries, (ii) multivalent interactions of carrier with endothelium, (iii) anchoring to multiple determinants, (iv) accessibility of binding sites and cellular response to their engagement, (v) role of cell phenotype and microenvironment in targeting, (vi) optimization of targeting by lowering carrier avidity, (vii) endocytosis of multivalent carriers via molecules not implicated in internalization of their ligands, and (viii) modulation of cellular uptake and trafficking by selection of specific epitopes on the target determinant, carrier geometry, and hydrodynamic factors. Refinement of these aspects and improving our understanding of vascular biology and pathology is likely to enable the clinical translation of vascular endothelial targeting of nanocarriers. PMID:24787360

  12. DNA Nanocarriers for Systemic Administration: Characterization and In Vivo Bioimaging in Healthy Mice

    PubMed Central

    David, Stephanie; Passirani, Catherine; Carmoy, Nathalie; Morille, Marie; Mevel, Mathieu; Chatin, Benoit; Benoit, Jean-Pierre; Montier, Tristan; Pitard, Bruno

    2013-01-01

    We hereby present different DNA nanocarriers consisting of new multimodular systems (MMS), containing the cationic lipid dioleylaminesuccinylparomomycin (DNA MMS DOSP), or bis (guanidinium)-tren-cholesterol (DNA MMS BGTC), and DNA lipid nanocapsules (DNA LNCs). Active targeting of the asialoglycoprotein receptor (ASGP-R) using galactose as a ligand for DNA MMS (GAL DNA MMS) and passive targeting using a polyethylene glycol coating for DNA LNCs (PEG DNA LNCs) should improve the properties of these DNA nanocarriers. All systems were characterized via physicochemical methods and the DNA payload of DNA LNCs was quantified for the first time. Afterwards, their biodistribution in healthy mice was analyzed after encapsulation of a fluorescent dye via in vivo biofluorescence imaging (BFI), revealing various distribution profiles depending on the cationic lipid used and their surface characteristics. Furthermore, the two vectors with the best prolonged circulation profile were administered twice in healthy mice revealing that the new DNA MMS DOSP vectors showed no toxicity and the same distribution profile for both injections, contrary to PEG DNA LNCs which showed a rapid clearance after the second injection, certainly due to the accelerated blood clearance phenomenon. PMID:23299832

  13. Programmed packaging of mesoporous silica nanocarriers for matrix metalloprotease 2-triggered tumor targeting and release.

    PubMed

    Zou, Zhen; He, Xiaoxiao; He, Dinggeng; Wang, Kemin; Qing, Zhihe; Yang, Xue; Wen, Li; Xiong, Jun; Li, Liling; Cai, Linli

    2015-07-01

    The development of multifunctional nanocarrier with each unit functioning at the correct time and location is a challenge for clinical applications. With this in mind, a type of intelligent mesoporous silica nanocarrier (PGFMSN) is proposed for matrix metalloprotease 2 (MMP 2)-triggered tumor targeting and release by integrating programmed packing and MMP 2-degradable gelatin. Mesoporous silica nanoparticles (MSN) are first functionalized with folic acid (FA) as a target ligand to improve cell uptake. Then gelatin is introduced onto FA-MSN via temperature-induced gelation, where gelatin layer blocks drugs inside the mesopores and protects the targeting ligand. To prolong blood-circulation lifetime, PEG is further decorated to obtain PGFMSN. All units are programmatically incorporated in a simple way and coordinated in an optimal fashion. Cells, multicellular spheroids and in vivo results demonstrate that PGFMSN is shielded against nonspecific uptake. After circulating to tumor tissue, the up-regulated MMP-2 hydrolyzes gelatin layer to deshield PEG and switch on the function of FA, which facilitate the selective uptake by tumor cells through folate-receptor-mediated endocytosis. Meanwhile, the packaged drug is released due to the shedding of gelatin layer. It is shown that doxorubicin (DOX)-loaded exhibits superior tumor targeting, drug internalization, cytotoxicity, and antitumor efficacy over free DOX, non-PEGylated and non-targeted nanoparticles, which provides potential applications for targeted cancer therapy. PMID:25941780

  14. Nanocarriers and their Actions to Improve Skin Permeability and Transdermal Drug Delivery.

    PubMed

    Khan, Nauman R; Harun, Mohd S; Nawaz, Asif; Harjoh, Nurulaini; Wong, Tin W

    2015-01-01

    Transdermal drug delivery is impeded by the natural barrier of epidermis namely stratum corneum. This limits the route to transport of drugs with a log octanol-water partition coefficient of 1 to 3, molecular weight of less than 500 Da and melting point of less than 200°C. Nanotechnology has received widespread investigation as nanocarriers are deemed to be able to fluidize the stratum corneum as a function of size, shape, surface charges, and hydrophilicity-hydrophobicity balance, while delivering drugs across the skin barrier. This review provides an overview and update on the latest designs of liposomes, ethosomes, transfersomes, niosomes, magnetosomes, oilin- water nanoemulsions, water-in-oil nanoemulsions, bicontinuous nanoemulsions, covalently crosslinked polysaccharide nanoparticles, ionically crosslinked polysaccharide nanoparticles, polyelectrolyte coacervated nanoparticles and hydrophobically modified polysaccharide nanoparticles with respect to their ability to fuse or fluidize lipid/protein/tight junction regimes of skin, and effect changes in skin permeability and drug flux. Universal relationships of nanocarrier size, zeta potential and chemical composition on transdermal permeation characteristics of drugs will be developed and discussed. PMID:25925113

  15. Transition metal-catalyzed one-pot synthesis of water-soluble dendritic molecular nanocarriers.

    PubMed

    Chen, Guanghui; Guan, Zhibin

    2004-03-10

    Here, we report the first example of transition metal-catalyzed one-pot synthesis of water-soluble dendritic molecular nanocarriers behaving like unimolecular micelles. Using the palladium-alpha-diimine chain walking catalyst, copolymerization of ethylene and comonomer 3 afforded, in one step, amphiphilic copolymer 1 having a hydrophobic core and a hydrophilic shell. A much larger amphiphilic core-shell copolymer 2 was synthesized by a two-step approach: a copolymer having many free hydroxyl groups was first prepared, which was subsequently coupled to poly(ethylene glycol) (PEG) to afford the copolymer 2. Light-scattering, fluorescence, and UV/vis spectroscopic studies with Nile Red in aqueous solution showed unimolecular micellar properties for both copolymers 1 and 2. The dye encapsulation capacity for the core-shell copolymers is nearly proportional to the molecular weight of the hydrophobic core. The unimolecular micellar properties coupled with the good water solubility and biocompatibility of the PEG moieties make these molecular nanocarriers promising candidates for many applications including drug delivery and controlled drug release. PMID:14995158

  16. Stimuli-responsive HBPS-g-PDMAEMA and its application as nanocarrier in loading hydrophobic molecules

    PubMed Central

    Chen, Yongsheng; Zain-Ul-Abdin; Sun, Ruoli; Jing, Guanghui; Tong, Rongbai; Deng, Zheng

    2016-01-01

    Summary The topic of stimuli-responsive nanocarriers for loading guest molecules is dynamic. It has been widely studied in applications including drug controlled release, smart sensing, catalysis, and modeling. In this paper, a graft copolymer (hyperbranched polystyrene)-g-poly[2-(dimethylamino)ethyl methacrylate] (HBPS-g-PDMAEMA) was synthesized and characterized by 1H NMR and GPC. It was observed that the star-like HBPS-g-PDMAEMA formed aggregates in aqueous solution. The influence of polymer concentration, ionic strength and pH value on the aggregates in aqueous solution was investigated by using UV–vis spectroscopy and DLS analysis. The results showed that size of aggregates was affected by a corresponding stimulus. In addition, the loading ability of HBPS-g-PDMAEMA aggregates was investigated by using pyrene or Nile red as the model guest molecules by using UV–vis and fluorescence spectroscopy. The results showed that HBPS-g-PDMAEMA aggregates were capable to encapsulate small hydrophobic molecules. These newly prepared HBPS-g-PDMAEMA nanocarriers might be used in, e.g., medicine or catalysis. PMID:27340484

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

    NASA Astrophysics Data System (ADS)

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

    2012-11-01

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

  18. Evaluating the effects of crystallinity in new biocompatible polyester nanocarriers on drug release behavior

    PubMed Central

    Karavelidis, Vassilios; Karavas, Evangelos; Giliopoulos, Dimitrios; Papadimitriou, Sofia; Bikiaris, Dimitrios

    2011-01-01

    Four new polyesters based on 1,3-propanediol and different aliphatic dicarboxylic acids were used to prepare ropinirole HCl-loaded nanoparticles. The novelty of this study lies in the use of polyesters with similar melting points but different degrees of crystallinity, varying from 29.8% to 67.5%, as drug nanocarriers. Based on their toxicity to human umbilical vein endothelial cells, these aliphatic polyesters were found to have cytotoxicity similar to that of polylactic acid and so may be considered as prominent drug nanocarriers. Drug encapsulation in polyesters was performed via an emulsification/solvent evaporation method. The mean particle size of drug-loaded nanoparticles was 164–228 nm, and the drug loading content was 16%–23%. Wide angle X-ray diffraction patterns showed that ropinirole HCl existed in an amorphous state within the nanoparticle polymer matrices. Drug release diagrams revealed a burst effect for ropinirole HCl in the first 6 hours, probably due to release of drug located on the nanoparticle surface, followed by slower release. The degree of crystallinity of the host polymer matrix seemed to be an important parameter, because higher drug release rates were observed in polyesters with a low degree of crystallinity. PMID:22162659

  19. Preparation, characterization, and in vitro antimicrobial assessment of nanocarrier based formulation of nadifloxacin for acne treatment.

    PubMed

    Kumar, A; Agarwal, S P; Ahuja, A; Ali, J; Choudhry, R; Baboota, S

    2011-02-01

    The objective of the present study was to develop a nanocarrier based formulation of nadifloxacin and to investigate its in vitro antimicrobial effect against Propionibacterium acnes. Nanocarrier based microemulsion formulations were prepared by aqueous titration method, using oleic acid as oil phase, Tween-80 as surfactant and ethanol as co-surfactant in different ratios. This procedure yielded monodisperse microemulsions exhibiting a mean droplet size in the range of 95-560 nm. This range of particle size is good to treat follicle related disorders like acne vulgaris because the size of follicles is in the range of 50-100 microm. Furthermore the optimized formulations were characterized for surface morphology by transmission electron microscopy and refractive index. The permeation studies were carried out using rat skin mounted in Franz diffusion cells. Flux of the optimised formulation was 2.24 times that of control. The diameter of inhibition zone of the microemulsion was found good but smaller than that of a clindamycin disc because of the higher therapeutic efficacy of clindamycin against P. acnes. The results indicated that the developed microemulsion shows promising results against P. acnes bacteria and may be a good approach for acne treatment. PMID:21434572

  20. Stimuli-responsive HBPS-g-PDMAEMA and its application as nanocarrier in loading hydrophobic molecules.

    PubMed

    Chen, Yongsheng; Wang, Li; Yu, Haojie; Zain-Ul-Abdin; Sun, Ruoli; Jing, Guanghui; Tong, Rongbai; Deng, Zheng

    2016-01-01

    The topic of stimuli-responsive nanocarriers for loading guest molecules is dynamic. It has been widely studied in applications including drug controlled release, smart sensing, catalysis, and modeling. In this paper, a graft copolymer (hyperbranched polystyrene)-g-poly[2-(dimethylamino)ethyl methacrylate] (HBPS-g-PDMAEMA) was synthesized and characterized by (1)H NMR and GPC. It was observed that the star-like HBPS-g-PDMAEMA formed aggregates in aqueous solution. The influence of polymer concentration, ionic strength and pH value on the aggregates in aqueous solution was investigated by using UV-vis spectroscopy and DLS analysis. The results showed that size of aggregates was affected by a corresponding stimulus. In addition, the loading ability of HBPS-g-PDMAEMA aggregates was investigated by using pyrene or Nile red as the model guest molecules by using UV-vis and fluorescence spectroscopy. The results showed that HBPS-g-PDMAEMA aggregates were capable to encapsulate small hydrophobic molecules. These newly prepared HBPS-g-PDMAEMA nanocarriers might be used in, e.g., medicine or catalysis. PMID:27340484

  1. Nanocarriers Conjugated with Cell Penetrating Peptides: New Trojan Horses by Modern Ulysses.

    PubMed

    Zappavigna, Silvia; Misso, Gabriella; Falanga, Annarita; Perillo, Emiliana; Novellino, Ettore; Galdiero, Massimiliano; Grieco, Paolo; Caraglia, Michele; Galdiero, Stefania

    2016-01-01

    Nanomedicine has opened the way to the design of more efficient diagnostics and therapeutics. Moreover, recent literature has illustrated the use of short cationic and/or amphipathic peptides, known as cell-penetrating peptides (CPPs), for mediating advanced drug delivery. CPPs exploit their ability to enter cells and enhance the uptake of many cargoes ranging from small molecules to proteins. The distinctive properties of nanocarriers (NC) based systems provide unforeseen benefits over pure drugs for biomedical applications and constitute a challenging research field particularly focused on imaging and delivery; nonetheless, several problems have to be overcome to make them a viable option in clinic. The use of CPPs improves significantly their delivery to specific intracellular targets and thus readily contributes to their use both for effective tumor therapy and gene therapy. A key issue is related to their mechanism of uptake, because although classical CPPs enhance NCs' uptake, the entry mechanism involves the endocytic pathway, which means that the delivered material is sequestered within vesicles and only a small amount will escape from this environment and reach the desired target. In this review, we will summarize recent advances in the use of CPP for enhanced delivery of nanocarriers, nucleic acids, and drugs, we will discuss their uptake mechanisms and we will describe novel approaches to improve endosomal escape of internalized nanosystems. PMID:27087493

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

    PubMed

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

    2016-08-01

    Oral colon-targeted drug delivery has attracted many researchers because of its distinct advantages of increasing the bioavailability of the drug at the target site and reducing the side effects. Polysaccharides that are precisely activated by the physiological environment of the colon hold greater promise for colon targeting. Considerable research efforts have been directed towards developing polysaccharide-based micro/nanocarriers. Types of polysaccharides for colon targeting and in vitro/in vivo assessments of polysaccharide-based carriers for oral colon-targeted drug delivery are summarised. Polysaccharide-based microspheres have gained increased importance not just for the delivery of the drugs for the treatment of local diseases associated with the colon (colon cancer, inflammatory bowel disease (IBD), amoebiasis and irritable bowel syndrome (IBS)), but also for it's potential for the delivery of anti-rheumatoid arthritis and anti-chronic stable angina drugs. Besides, Polysaccharide-based micro/nanocarriers such as microbeads, microcapsules, microparticles, nanoparticles, nanogels and nanospheres are also introduced in this review. PMID:26766303

  3. Chitosan derivatives as effective nanocarriers for ocular release of timolol drug.

    PubMed

    Siafaka, Panoraia I; Titopoulou, Alexandra; Koukaras, Emmanuel N; Kostoglou, Margaritis; Koutris, Efthimios; Karavas, Evangelos; Bikiaris, Dimitrios N

    2015-11-10

    The aim of the present study was to evaluate the effectiveness of neat chitosan (CS) and its derivatives with succinic anhydride (CSUC) and 2-carboxybenzaldehyde (CBCS) as appropriate nanocarriers for ocular release of timolol maleate (Tim). Drug nanoencapsulation was performed via ionic crosslinking gelation of the used carriers and sodium tripolyphosphate (TPP). Nanoparticles with size ranged from about 190 to 525 nm were prepared and it was found that the formed size was directly depended on the used carrier and their ratios with TPP. For CS derivatives it was found that as the amount of TPP increased, the particle size increased too, while both derivatives proceeded to nanoparticles with smaller size than that of neat CS. The interactions between carriers and TPP were studied theoretically using all-electron calculations within the framework of density functional theory (DFT). In most of nanoparticles formulations, Tim was entrapped in amorphous form, while the drug entrapment efficiency was higher in CBCS derivative.It was indicated that Tim release rate depended mainly on the used carrier, particle size of prepared nanocarriers and drug loading. From the theoretical release data analysis, it was found that the Tim release was a stagewise procedure with drug diffusion being the dominant release mechanism for each stage. PMID:26341322

  4. Scalable imprinting of shape-specific polymeric nanocarriers using a release layer of switchable water solubility.

    PubMed

    Agarwal, Rachit; Singh, Vikramjit; Jurney, Patrick; Shi, Li; Sreenivasan, S V; Roy, Krishnendu

    2012-03-27

    There is increasing interest in fabricating shape-specific polymeric nano- and microparticles for efficient delivery of drugs and imaging agents. The size and shape of these particles could significantly influence their transport properties and play an important role in in vivo biodistribution, targeting, and cellular uptake. Nanoimprint lithography methods, such as jet-and-flash imprint lithography (J-FIL), provide versatile top-down processes to fabricate shape-specific, biocompatible nanoscale hydrogels that can deliver therapeutic and diagnostic molecules in response to disease-specific cues. However, the key challenges in top-down fabrication of such nanocarriers are scalable imprinting with biological and biocompatible materials, ease of particle-surface modification using both aqueous and organic chemistry as well as simple yet biocompatible harvesting. Here we report that a biopolymer-based sacrificial release layer in combination with improved nanocarrier-material formulation can address these challenges. The sacrificial layer improves scalability and ease of imprint-surface modification due to its switchable solubility through simple ion exchange between monovalent and divalent cations. This process enables large-scale bionanoimprinting and efficient, one-step harvesting of hydrogel nanoparticles in both water- and organic-based imprint solutions. PMID:22385068

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

    PubMed

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

    2015-10-01

    Soluthin MD(®), a unique phosphatidylcholine-maltodextrin based hydrophilic lipopolysaccharide, which exhibits superior biocompatibility and bioavailability enhancer properties for poorly water soluble drug(s). Curcumin (CUR) is a potential natural anticancer drug with low bioavailability due to poor aqueous solubility. The study aims at formulation and optimization of CUR loaded lipopolysaccharide nanocarriers (C-LPNCs) to enhance oral bioavailability and anticancer efficacy in colon-26 tumor-bearing mice in vitro and in vivo. The Optimized C-LPNCs demonstrated favorable mean particle size (108 ± 3.4 nm) and percent entrapment efficiency (65.29 ± 1.0%). Pharmacokinetic parameters revealed ∼130-fold increase in oral bioavailability and cytotoxicity studies demonstrated ∼23-fold reduction in 50% cell growth inhibition when treated with optimized C-LPNCs as compared to pure CUR. In vivo anticancer study performed with optimized C-LPNCs showed significant increase in efficacy compared with pure CUR. Thus, lipopolysaccharide nanocarriers show potential delivery strategy to improve oral bioavailability and anticancer efficacy of CUR in the treatment of colorectal cancer. PMID:26076595

  6. Self-Assembled Polymeric Micellar Nanoparticles as Nanocarriers for Poorly Soluble Anticancer Drug Ethaselen

    NASA Astrophysics Data System (ADS)

    Li, Xinru; Yang, Zhuoli; Yang, Kewei; Zhou, Yanxia; Chen, Xingwei; Zhang, Yanhui; Wang, Fei; Liu, Yan; Ren, Lijun

    2009-12-01

    A series of monomethoxy poly(ethylene glycol)-poly(lactide) (mPEG-PLA) diblock copolymers were synthesized, and mPEG-PLA micelle was fabricated and used as a nanocarrier for solubilization and delivery of a promising anticancer drug ethaselen. Ethaselen was efficiently encapsulated into the micelles by the dialysis method, and the solubility of ethaselen in water was remarkably increased up to 82 μg/mL before freeze-drying. The mean diameter of ethaselen-loaded micelles ranged from 51 to 98 nm with a narrow size distribution and depended on the length of PLA block. In vitro hemolysis study indicated that mPEG-PLA copolymers and ethaselen-loaded polymeric micelles had no hemolytic effect on the erythrocyte. The enhanced antitumor efficacy and reduced toxic effect of ethaselen-loaded polymeric micelle when compared with ethaselen-HP-β-CD inclusion were observed at the same dose in H22 human liver cancer cell bearing mouse models. These suggested that mPEG-PLA polymeric micelle nanoparticles had great potential as nanocarriers for effective solubilization of poorly soluble ethaselen and further reducing side effects and toxicities of the drug.

  7. Cyclodextrin conjugated magnetic colloidal nanoparticles as a nanocarrier for targeted anticancer drug delivery

    NASA Astrophysics Data System (ADS)

    Banerjee, Shashwat S.; Chen, Dong-Hwang

    2008-07-01

    A novel magnetic nanocarrier (CD-GAMNPs) was fabricated for targeted anticancer drug delivery by grafting cyclodextrin (CD) onto gum arabic modified magnetic nanoparticles (GAMNPs) using hexamethylene diisocyanate (HMDI) as a linker. Analyses by transmission electron microscopy (TEM) and dynamic light scattering (DLS) revealed that the product had a mean diameter of 17.1 nm and a mean hydrodynamic diameter of 44.1 nm. The CD grafting was confirmed by Fourier transform infrared (FTIR) spectroscopy, and thermogravimetric analysis (TGA) indicated that the amount of CD grafted on the GAMNPs was 16.8 mg g-1. The study on the loading of anticancer drug all-trans-retinoic acid (retinoic acid) revealed that the newly fabricated magnetic nanocarrier possessed a considerably higher adsorption capability as compared to GAMNPs due to the special hydrophobic cavity structure of CD, which could act as a host-guest complex with retinoic acid. Furthermore, it was found that the complexation of CD-GAMNPs with retinoic acid was exothermic and the presence of a surfactant (sodium dodecyl sulfate) led to the decrease in the inclusion of retinoic acid because the linear structure of sodium dodecyl sulfate made it easier to enter the cavity of CD as compared to less linear retinoic acid. In addition, the in vitro release profile of retinoic acid from CD-GAMNPs was characterized by an initial fast release followed by a delayed release phase.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-07-01

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

  11. Calcium phosphate-based organic-inorganic hybrid nanocarriers with pH-responsive on/off switch for photodynamic therapy.

    PubMed

    Nomoto, Takahiro; Fukushima, Shigeto; Kumagai, Michiaki; Miyazaki, Kozo; Inoue, Aki; Mi, Peng; Maeda, Yoshinori; Toh, Kazuko; Matsumoto, Yu; Morimoto, Yuji; Kishimura, Akihiro; Nishiyama, Nobuhiro; Kataoka, Kazunori

    2016-05-26

    Photodynamic therapy (PDT) is a promising treatment modality for malignant tumors in a light-selective manner. To improve the PDT efficacy, numerous kinds of nanocarriers have been developed to deliver photosensitizers (PSs) selectively into the tumor through leaky tumor-associated vasculature. However, the corresponding prolonged retention of the nanocarrier in the bloodstream may lead to unfavorable photochemical damage to normal tissues such as skin. Here, we report an organic-inorganic hybrid nanocarrier with a pH-responsive on/off switch of PDT efficacy. This hybrid nanocarrier is constructed by hydrothermal synthesis after simple mixing of calcium/phosphate ions, chlorin e6 (amphiphilic low molecular weight PS), and poly(ethylene glycol)-b-poly(aspartic acid) (PEG-PAsp) copolymers in an aqueous solution. The hybrid nanocarrier possesses a calcium phosphate (CaP) core encapsulating the PSs, which is surrounded by a PEG shielding layer. Under physiological conditions (pH 7.4), the nanocarrier suppressed the photochemical activity of PS by lowering the access of oxygen molecules to the incorporated PS, while PDT efficacy was restored in a pH-responsive manner because of the dissolution of CaP and eventual recovery of access between the oxygen and the PS. Owing to this switch, the nanocarrier reduced the photochemical damage in the bloodstream, while it induced effective PDT efficacy inside the tumor cell in response to the acidic conditions of the endo-/lysosomes. PMID:26971562

  12. Insight into the Modification of Polymeric Micellar and Liposomal Nanocarriers by Fluorescein-Labeled Lipids and Uptake-Mediating Lipopeptides.

    PubMed

    Draffehn, Sören; Eichhorst, Jenny; Wiesner, Burkhard; Kumke, Michael U

    2016-07-12

    Encapsulation of diagnostic and therapeutic compounds in transporters improves their delivery to the point of need. An even more efficient treatment of diseases can be achieved using carriers with targeting or protecting moieties. In the present work, we investigated micellar and liposomal nanocarriers modified with fluorescein, peptides, and polymers that are covalently bound to fatty acids or phospholipids to ensure a self-driven incorporation into the micelles or liposomes. First, we characterized the photophysics of the fluorescent probes in the absence and in the presence of nanocarriers. Changes in the fluorescence decay time, quantum yield, and intensity of a fluorescein-labeled fatty acid (fluorescein-labeled palmitic acid [fPA]) and a fluorescein-labeled lipopeptide (P2fA2) were found. By exploiting these changes, we investigated a lipopeptide (P2A2 as an uptake-mediating unit) in combination with different nanocarriers (micelles and liposomes) and determined the corresponding association constant Kass values, which were found to be very high. In addition, the mobility of fPA was exploited using fluorescence correlation spectroscopy (FCS) and fluorescence depolarization (FD) experiments to characterize the nanocarriers. Cellular uptake experiments with mouse brain endothelial cells provided information on the uptake behavior of liposomes modified by uptake-mediating P2A2 and revealed differences in the uptake behavior between pH-sensitive and pH-insensitive liposomes. PMID:27295095

  13. A comparative study of curcumin-loaded lipid-based nanocarriers in the treatment of inflammatory bowel disease.

    PubMed

    Beloqui, Ana; Memvanga, Patrick B; Coco, Régis; Reimondez-Troitiño, Sonia; Alhouayek, Mireille; Muccioli, Giulio G; Alonso, María José; Csaba, Noemi; de la Fuente, María; Préat, Véronique

    2016-07-01

    Selective drug delivery to inflamed tissues is of widespread interest for the treatment of inflammatory bowel disease (IBD). Because a lack of physiological lipids has been described in patients suffering IBD, and some lipids present immunomodulatory properties, we hypothesize that the combination of lipids and anti-inflammatory drugs together within a nanocarrier may be a valuable strategy for overcoming IBD. In the present study, we investigated and compared the in vitro and in vivo efficacy of three lipid-based nanocarriers containing curcumin (CC) as an anti-inflammatory drug for treating IBD in a murine DSS-induced colitis model. These nanocarriers included self-nanoemulsifying drug delivery systems (SNEDDS), nanostructured lipid carriers (NLC) and lipid core-shell protamine nanocapsules (NC). In vitro, a 30-fold higher CC permeability across Caco-2 cell monolayers was obtained using NC compared to SNEDDS (NC>SNEDDS>NLC and CC suspension). The CC SNEDDS and CC NLC but not the CC NC or CC suspension significantly reduced TNF-α secretion by LPS-activated macrophages (J774 cells). In vivo, only CC NLC were able to significantly decrease neutrophil infiltration and TNF-α secretion and, thus, colonic inflammation. Our results show that a higher CC permeability does not correlate with a higher efficacy in IBD treatment, which suggests that lipidic nanocarriers exhibiting increased CC retention at the intestinal site, rather than increased CC permeability are efficient treatments of IBD. PMID:27022873

  14. Anticancer Therapy: Light-Activated Hypoxia-Responsive Nanocarriers for Enhanced Anticancer Therapy (Adv. Mater. 17/2016).

    PubMed

    Qian, Chenggen; Yu, Jicheng; Chen, Yulei; Hu, Quanyin; Xiao, Xuanzhong; Sun, Wujin; Wang, Chao; Feng, Peijian; Shen, Qun-Dong; Gu, Zhen

    2016-05-01

    A light-activated hypoxia-responsive drug-delivery vehicle is described by Q.-D. Shen, Z. Gu, and co-workers on page 3313. This conjugated-polymer-based nanocarrier can be activated by photoirradiation, producing singlet oxygen ((1) O2 ) and inducing hypoxia to promote release of its cargo inside tumor cells for enhanced anticancer efficacy. PMID:27122110

  15. Protein adsorption is required for stealth effect of poly(ethylene glycol)- and poly(phosphoester)-coated nanocarriers.

    PubMed

    Schöttler, Susanne; Becker, Greta; Winzen, Svenja; Steinbach, Tobias; Mohr, Kristin; Landfester, Katharina; Mailänder, Volker; Wurm, Frederik R

    2016-04-01

    The current gold standard to reduce non-specific cellular uptake of drug delivery vehicles is by covalent attachment of poly(ethylene glycol) (PEG). It is thought that PEG can reduce protein adsorption and thereby confer a stealth effect. Here, we show that polystyrene nanocarriers that have been modified with PEG or poly(ethyl ethylene phosphate) (PEEP) and exposed to plasma proteins exhibit a low cellular uptake, whereas those not exposed to plasma proteins show high non-specific uptake. Mass spectrometric analysis revealed that exposed nanocarriers formed a protein corona that contains an abundance of clusterin proteins (also known as apolipoprotein J). When the polymer-modified nanocarriers were incubated with clusterin, non-specific cellular uptake could be reduced. Our results show that in addition to reducing protein adsorption, PEG, and now PEEPs, can affect the composition of the protein corona that forms around nanocarriers, and the presence of distinct proteins is necessary to prevent non-specific cellular uptake. PMID:26878141

  16. Protein adsorption is required for stealth effect of poly(ethylene glycol)- and poly(phosphoester)-coated nanocarriers

    NASA Astrophysics Data System (ADS)

    Schöttler, Susanne; Becker, Greta; Winzen, Svenja; Steinbach, Tobias; Mohr, Kristin; Landfester, Katharina; Mailänder, Volker; Wurm, Frederik R.

    2016-04-01

    The current gold standard to reduce non-specific cellular uptake of drug delivery vehicles is by covalent attachment of poly(ethylene glycol) (PEG). It is thought that PEG can reduce protein adsorption and thereby confer a stealth effect. Here, we show that polystyrene nanocarriers that have been modified with PEG or poly(ethyl ethylene phosphate) (PEEP) and exposed to plasma proteins exhibit a low cellular uptake, whereas those not exposed to plasma proteins show high non-specific uptake. Mass spectrometric analysis revealed that exposed nanocarriers formed a protein corona that contains an abundance of clusterin proteins (also known as apolipoprotein J). When the polymer-modified nanocarriers were incubated with clusterin, non-specific cellular uptake could be reduced. Our results show that in addition to reducing protein adsorption, PEG, and now PEEPs, can affect the composition of the protein corona that forms around nanocarriers, and the presence of distinct proteins is necessary to prevent non-specific cellular uptake.

  17. Core-shell nanocarriers with ZnO quantum dots-conjugated Au nanoparticle for tumor-targeted drug delivery.

    PubMed

    Chen, Tong; Zhao, Tong; Wei, Dongfeng; Wei, Yanxia; Li, Yuanyuan; Zhang, Haixia

    2013-02-15

    Core-shell structured multifunctional nanocarriers (NCs) of ZnO quantum dots-conjugated gold nanoparticles (Au NPs) as core and amphiphilic hyperbranched block copolymer as shell were synthesized for targeted anticancer drug delivery. The amphiphilic hyperbranched block copolymer contained poly(l-lactide) (PLA) inner arm and folate (FA)-conjugated a sulfated polysaccharide from Gynostemma pentaphyllum Makino (GPPS-FA) outer arm. The structure and properties of core-shell structured multifunctional nanocarriers were characterized and determined by UV-visible spectra, FT-IR spectra, X-ray diffraction (XRD), fluorescence spectroscopy and TEM analyses. The release results indicated that camptothecin (CPT) release from NCs at pH 7.4 was much greater than that at pH 5.3. The cytotoxicity studies showed that both the blank NCs and the CPT-loaded NCs provided high anticancer activity against Hela cells. Furthermore, nanocarriers gained specificity to target model cancer cells in this study due to the enhanced cell uptake mediated by FA moiety. The results indicated that the NCs not only had great potential as tumor-targeted drug delivery nanocarrier, but also had an assistant role in the treatment of cancer. PMID:23399137

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

    NASA Astrophysics Data System (ADS)

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

    2015-06-01

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

  19. Hydrodynamic interactions of deformable polymeric nanocarriers and the effect of crosslinking

    PubMed Central

    Sarkar, Arijit; Eckmann, David M.; Ayyaswamy, Portonovo S.

    2015-01-01

    We report theoretical as well as numerical investigations of deformable nanocarriers (NCs) under physiologically relevant flow conditions. Specifically, to model the deformable lysozyme-core/dextran-shell crosslinked polymer based NC with internal nanostructure and subject it to external hydrodynamic shear, we have introduced a coarse-grained model for the NC and have adopted a Brownian dynamics framework, which incorporates hydrodynamic interactions, in order to describe the static and dynamic properties of the NC. In order to represent the fluidity of the polymer network in the dextran brush-like corona, we coarse-grain the structure of the NC based on the hypothesis that Brownian motion, polymer melt reptations, and crosslinking density dominate their structure and dynamics. In our model, we specify a crosslinking density and employ the simulated annealing protocol to mimic the experimental synthesis steps in order to obtain the appropriate internal structure of the core–shell polymer. We then compute the equilibrium as well as steady shear rheological properties as functions of the Péclet number and the crosslinking density, in the presence of hydrodynamic interactions. We find that with increasing crosslinking, the stiffness of the nano-carrier increases, the radius of gyration decreases, and as a consequence the self-diffusivity increases. The nanocarrier under shear deforms and orients along the direction of the applied shear and we find that the orientation and deformation under shear are dependent on the shear rate and the crosslinking density. We compare various dynamic properties of the NC as a function of the shear force, such as orientation, deformation, intrinsic stresses etc., with previously reported computational and experimental results of other model systems. The computational approach described here serves as a powerful tool for the rational design of NCs by taking both the physiological as well as the hydrodynamic environments into

  20. Non-viral nanocarriers for siRNA delivery in breast cancer

    PubMed Central

    Zhang, Jing; Li, Xiang; Huang, Leaf

    2014-01-01

    Breast cancer is the most frequently diagnosed malignancy in American women. While significant progress has been made in development of modern diagnostic tools and surgical treatments, only marginal improvements have been achieved with relapsed metastatic breast cancer. Small interfering RNAs (siRNAs) mediate gene silencing of a target protein by disrupting messenger RNAs in an efficient and sequence-specific manner. One application of this technology is the knockdown of genes responsible for tumorigenesis, including those driving oncogenesis, survival, proliferation and death of cells, angiogenesis, invasion and metastasis, and resistance to treatment. Non-viral nanocarriers have attracted attention based on their potential for targeted delivery of siRNA and efficient gene silencing without toxicity. Here, we review promising, non-viral delivery strategies employing liposomes, nanoparticles and inorganic materials in breast cancer. PMID:24874288

  1. Charged pullulan derivatives for the development of nanocarriers by polyelectrolyte complexation.

    PubMed

    Dionísio, M; Braz, L; Corvo, M; Lourenço, J P; Grenha, A; Rosa da Costa, A M

    2016-05-01

    Pullulan, a neutral polysaccharide, was chemically modified in order to obtain two charged derivatives: reaction with SO3(.)DMF complex afforded a sulfate derivative (SP), while reaction with glycidyltrimethylammonium chloride gave a quaternary ammonium salt (AP). The presence of the charged groups was confirmed by FTIR. Assessment of the positions where the reaction took place was based on (1)H- and (13)C NMR (COSY, HSQC-TOCSY, HSQC-DEPT, and HMBC) experiments. Estimation of the degree of substitution (DS) was made from elemental analysis data, and further confirmed by NMR peak areas in the case of AP. These new derivatives showed the capability to condense with each other, forming nanoparticles with the ability to associate a model protein (BSA) and displaying adequate size for drug delivery applications, therefore making them good candidates for the production of pullulan-based nanocarriers by polyelectrolyte complexation. PMID:26800902

  2. Nanocarrier-mediated co-delivery of chemotherapeutic drugs and gene agents for cancer treatment.

    PubMed

    Kang, Lin; Gao, Zhonggao; Huang, Wei; Jin, Mingji; Wang, Qiming

    2015-05-01

    The efficacy of chemotherapeutic drug in cancer treatment is often hampered by drug resistance of tumor cells, which is usually caused by abnormal gene expression. RNA interference mediated by siRNA and miRNA can selectively knock down the carcinogenic genes by targeting specific mRNAs. Therefore, combining chemotherapeutic drugs with gene agents could be a promising strategy for cancer therapy. Due to poor stability and solubility associated with gene agents and drugs, suitable protective carriers are needed and have been widely researched for the co-delivery. In this review, we summarize the most commonly used nanocarriers for co-delivery of chemotherapeutic drugs and gene agents, as well as the advances in co-delivery systems. PMID:26579443

  3. Nanocarrier-mediated co-delivery of chemotherapeutic drugs and gene agents for cancer treatment

    PubMed Central

    Kang, Lin; Gao, Zhonggao; Huang, Wei; Jin, Mingji; Wang, Qiming

    2015-01-01

    The efficacy of chemotherapeutic drug in cancer treatment is often hampered by drug resistance of tumor cells, which is usually caused by abnormal gene expression. RNA interference mediated by siRNA and miRNA can selectively knock down the carcinogenic genes by targeting specific mRNAs. Therefore, combining chemotherapeutic drugs with gene agents could be a promising strategy for cancer therapy. Due to poor stability and solubility associated with gene agents and drugs, suitable protective carriers are needed and have been widely researched for the co-delivery. In this review, we summarize the most commonly used nanocarriers for co-delivery of chemotherapeutic drugs and gene agents, as well as the advances in co-delivery systems. PMID:26579443

  4. Non-polymeric nano-carriers in HIV/AIDS drug delivery and targeting.

    PubMed

    Gupta, Umesh; Jain, Narendra K

    2010-03-18

    Development of an effective drug delivery approach for the treatment of HIV/AIDS is a global challenge. The conventional drug delivery approaches including Highly Active Anti Retroviral Therapy (HAART) have increased the life span of the HIV/AIDS patient. However, the eradication of HIV is still not possible with these approaches due to some limitations. Emergence of polymeric and non-polymeric nanotechnological approaches can be opportunistic in this direction. Polymeric carriers like, dendrimers and nanoparticles have been reported for the targeting of anti HIV drugs. The synthetic pathways as well polymeric framework create some hurdles in their successful formulation development as well as in the possible drug delivery approaches. In the present article, we have discussed the general physiological aspects of the infection along with the relevance of non-polymeric nanocarriers like liposomes, solid lipid nanoparticles (SLN), ethosomes, etc. in the treatment of this disastrous disease. PMID:19913579

  5. Antimicrobial Peptide-Driven Colloidal Transformations in Liquid-Crystalline Nanocarriers.

    PubMed

    Gontsarik, Mark; Buhmann, Matthias T; Yaghmur, Anan; Ren, Qun; Maniura-Weber, Katharina; Salentinig, Stefan

    2016-09-01

    Designing efficient colloidal systems for the delivery of membrane active antimicrobial peptides requires in-depth understanding of their structural and morphological characteristics. Using dispersions of inverted type bicontinuous cubic phase (cubosomes), we examine the effect of integrating the amphiphilic peptide LL-37 at different concentrations on the self-assembled structure and evaluate its bactericidal ability against Escherichia coli. Small-angle X-ray scattering, dynamic light scattering, and cryogenic transmission electron microscopy show that LL-37 integrates into the bicontinuous cubic structure, inducing colloidal transformations to sponge and lamellar phases and micelles in a concentration-dependent manner. These investigations, together with in vitro evaluation studies using a clinically relevant bacterial strain, established the composition-nanostructure-activity relationship that can guide the design of new nanocarriers for antimicrobial peptides and may provide essential knowledge on the mechanisms underlying the bacterial membrane disruption with peptide-loaded nanostructures. PMID:27541048

  6. SWCNTs as novel theranostic nanocarriers for cancer diagnosis and therapy: towards safe translation to the clinics.

    PubMed

    Al Faraj, Achraf

    2016-06-01

    With their unique physicochemical properties, single walled carbon nanotubes (SWCNTs) hold great promise for applications as drug delivery systems (DDS) for early and better diagnosis and therapy of cancer. While several in vitro and in vivo studies have validated their potential benefit, no SWCNT-based formulation has yet reached clinical trials. Towards prospective safe clinical applications, the main properties that were adopted to enhance the biocompatibility of SWCNTs were highlighted. Then, the recent progresses in the in vivo applications of SWCNTs as diagnostic nanoprobes using multimodality imaging techniques and as therapeutic nanocarriers delivering wide range of anticancer efficient drugs to tumors were reviewed. Finally, the efforts required for safe clinical applications of SWCNTs as DDS for cancer diagnosis and therapy were discussed. PMID:27172091

  7. Multimodal magnetic nano-carriers for cancer treatment: Challenges and advancements

    NASA Astrophysics Data System (ADS)

    Aadinath, W.; Ghosh, Triroopa; Anandharamakrishnan, C.

    2016-03-01

    Iron oxide nanoparticles (IONPs) have been a propitious topic for cancer treatment in recent years because of its multifunctional theranostic applications under magnetic field. Two such widely used applications in cancer biology are gradient magnetic field guided targeting and alternative magnetic field (AMF) induced local hyperthermia. Gradient magnetic field guided targeting is a mode of active targeting of therapeutics conjugated with iron oxide nanoparticles. These particles also dissipate heat in presence of AMF which causes thermal injury to the cells of interest, for example tumour cells and subsequent death. Clinical trials divulge the feasibility of such magnetic nano-carrier as a promising candidate in cancer biology. However, these techniques need further investigations to curtail certain limitations manifested. Recent progresses in response have shrunken the barricade to certain extent. In this context, principles, challenges associated with these applications and recent efforts made in response will be discussed.

  8. Noscapine chemosensitization enhances docetaxel anticancer activity and nanocarrier uptake in triple negative breast cancer.

    PubMed

    Doddapaneni, Ravi; Patel, Ketan; Chowdhury, Nusrat; Singh, Mandip

    2016-08-01

    Chemosensitization and enhanced delivery to solid tumor are widely explored strategies to augment the anticancer efficacy of existing chemotherapeutics agents. The aim of current research was to investigate the role of low dose Noscapine (Nos) in potentiating docetaxel cytotoxicity and enhancing tumor penetration of nanocarriers. The objectives are; (1) To evaluate the chemo-sensitizing effect of Nos in combination with docetaxel (DTX), and to elucidate the possible mechanism (2) To investigate the effect of low dose Nos on tumor stroma and enhancing nanocarrier uptake in triple negative breast cancer (TNBC) bearing nude mice. Cytotoxicity and flow cytometry analysis of DTX in Nos (4µM) pre-treated MDA-MB-231 cells showed 3.0-fold increase in cell killing and 30% increase in number of late apoptotic cells, respectively. Stress transducer p38 phosphorylation was significantly upregulated with Nos exposure. DTX showed remarkable downregulation in expression of bcl-2, survivin and pAKT in Nos pre-treated MDA-MB-231 cells. Nos pre-sensitization significantly (p<0.02) enhanced the anti-migration effect of DTX. In vivo studies in orthotopic TNBC tumor bearing mice showed marked reduction in tumor collagen-I levels and significantly (p<0.03) higher intra-tumoral uptake of coumarin-6 loaded PEGylated liposomes (7-fold) in Nos treated group. Chemo-sensitization and anti-fibrotic effect of Nos could be a promising approach to increase anticancer efficacy of DTX which can be used for other nanomedicinal products. PMID:27177833

  9. Lyophilized phytosomal nanocarriers as platforms for enhanced diosmin delivery: optimization and ex vivo permeation

    PubMed Central

    Freag, May S; Elnaggar, Yosra SR; Abdallah, Ossama Y

    2013-01-01

    Diosmin (DSN) is an outstanding phlebotonic flavonoid with a tolerable potential for the treatment of colon and hepatocellular carcinoma. Being highly insoluble, DSN bioavailability suffers from high inter-subject variation due to variable degrees of permeation. This work endeavored to develop novel DSN loaded phytosomes in order to improve drug dissolution and intestinal permeability. Three preparation methods (solvent evaporation, salting out, and lyophilization) were compared. Nanocarrier optimization encompassed different soybean phospholipid (SPC) types, different solvents, and different DSN:SPC molar ratios (1:1, 1:2, and 1:4). In vitro appraisal encompassed differential scanning calorimetry, infrared spectroscopy, particle size, zeta potential, polydispersity index, transmission electron microscopy, drug content, and in vitro stability. Comparative dissolution studies were performed under sink versus non-sink conditions. Ex vivo intestinal permeation studies were performed on rats utilizing noneverted sac technique and high-performance liquid chromatography analysis. The results revealed lyophilization as the optimum preparation technique using SPC and solvent mixture (Dimethyl sulphoxide:t-butylalchol) in a 1:2 ratio. Complex formation was contended by differential scanning calorimetry and infrared data. Optimal lyophilized phytosomal nanocarriers (LPNs) exhibited the lowest particle size (316 nm), adequate zeta-potential (−27 mV), and good in vitro stability. Well formed, discrete vesicles were revealed by transmission electron microscopy, drug content, and in vitro stability. Comparative dissolution studies were performed. LPNs demonstrated significant enhancement in DSN dissolution compared to crude drug, physical mixture, and generic and brand DSN products. Permeation studies revealed 80% DSN permeated from LPNs via oxygenated rat intestine compared to non-detectable amounts from suspension. In this study, LPNs (99% drug loading) could be successfully

  10. Modulation of Endosomal Escape of IRQ-PEGylated Nano-carrier

    NASA Astrophysics Data System (ADS)

    Mudhakir, Diky; Akita, Hidetaka; Harashima, Hideyoshi

    2011-12-01

    The novel IRQ peptide is one of cell penetrating peptides (CPPs) that has ability to induce endosomal escape. It has been demonstrated that IRQ ligand had ability to facilitate an escape of liposomes encapsulating siRNA from the endosomes presumably by fusion-independent mechanism [1,2]. In the present study, we attempted to modulate the intracellular trafficking of IRQ-modified nano-carrier in term of escaping process by changing the lipid composition. The peptide was attached to the terminal end of maleimide group of polyethylene glycol-modified liposomes (IRQ-PEG-Lip). The liposomes were composed of DOTAP, DOPE and cholesterol and it was labeled by water soluble sulpho-rhodamine B (Sr-B). The escape of PEG-coated liposomes was then observed by confocal laser scanning microscope after the endosomes were stained with Lysosensor. The results exhibited that IRQ-PEG-Lip was escaped from endosomal compartment after 1 h transfection when 40% of DOPE was incorporated into the nanostructure comparing to that of PEG-Lip. These results are consistent with the previous results that the IRQ facilitates endosomal escape via independent-mechanism. However, IRQ-PEG-Lip were then completely co-localized in the acidic compartment when density of DOPE was reduced approximately 20%. These results indicated that the utilizing of DOPE is important for the escape process even in the presence of hydrophilic PEG polymer. In conclusion, the regulation of endosomal escape ability of the PEGylated-IRQ nano-carrier was induced by fusion-independent manner as well as fusogenic lipid.

  11. Surface-Adaptive, Antimicrobially Loaded, Micellar Nanocarriers with Enhanced Penetration and Killing Efficiency in Staphylococcal Biofilms.

    PubMed

    Liu, Yong; Busscher, Henk J; Zhao, Bingran; Li, Yuanfeng; Zhang, Zhenkun; van der Mei, Henny C; Ren, Yijin; Shi, Linqi

    2016-04-26

    Biofilms cause persistent bacterial infections and are extremely recalcitrant to antimicrobials, due in part to reduced penetration of antimicrobials into biofilms that allows bacteria residing in the depth of a biofilm to survive antimicrobial treatment. Here, we describe the preparation of surface-adaptive, Triclosan-loaded micellar nanocarriers showing (1) enhanced biofilm penetration and accumulation, (2) electrostatic targeting at acidic pH toward negatively charged bacterial cell surfaces in a biofilm, and (3) antimicrobial release due to degradation of the micelle core by bacterial lipases. First, it was established that mixed-shell-polymeric-micelles (MSPM) consisting of a hydrophilic poly(ethylene glycol) (PEG)-shell and pH-responsive poly(β-amino ester) become positively charged at pH 5.0, while being negatively charged at physiological pH. This is opposite to single-shell-polymeric-micelles (SSPM) possessing only a PEG-shell and remaining negatively charged at pH 5.0. The stealth properties of the PEG-shell combined with its surface-adaptive charge allow MSPMs to penetrate and accumulate in staphylococcal biofilms, as demonstrated for fluorescent Nile red loaded micelles using confocal-laser-scanning-microscopy. SSPMs, not adapting a positive charge at pH 5.0, could not be demonstrated to penetrate and accumulate in a biofilm. Once micellar nanocarriers are bound to a staphylococcal cell surface, bacterial enzymes degrade the MSPM core to release its antimicrobial content and kill bacteria over the depth of a biofilm. This constitutes a highly effective pathway to control blood-accessible staphylococcal biofilms using antimicrobials, bypassing biofilm recalcitrance to antimicrobial penetration. PMID:26998731

  12. Polycatechol nanosheet: a superior nanocarrier for highly effective chemo-photothermal synergistic therapy in vivo

    NASA Astrophysics Data System (ADS)

    Bai, J.; Jia, X. D.; Ma, Z. F.; Jiang, X. E.; Sun, X. P.

    2016-02-01

    The integration of phototherapy and chemotherapy in a single system holds great promise to improve the therapeutic efficacy of tumor treatment, but it remains a key challenge. In this study, we describe our recent finding that polycatechol nanosheet (PCCNS) can be facilely prepared on a large scale via chemical polymerization at 4 °C, as an effective nanocarrier for loading high-density CuS nanocrystals as a photothermal agent. The resulting CuS/PCCNS nanocomposites exhibit good biocompatibility, strong stability, and a high photothermal conversion efficiency of ~45.7%. The subsequent loading of anticancer drug doxorubicin (Dox) creates a superior theranostic agent with pH- and heat-responsive drug release, leading to almost complete destruction of mouse cervical tumor under NIR laser irradiation. This development offers an attractive theranostic agent for in vivo chemo-photothermal synergistic therapy toward biomedical applications.The integration of phototherapy and chemotherapy in a single system holds great promise to improve the therapeutic efficacy of tumor treatment, but it remains a key challenge. In this study, we describe our recent finding that polycatechol nanosheet (PCCNS) can be facilely prepared on a large scale via chemical polymerization at 4 °C, as an effective nanocarrier for loading high-density CuS nanocrystals as a photothermal agent. The resulting CuS/PCCNS nanocomposites exhibit good biocompatibility, strong stability, and a high photothermal conversion efficiency of ~45.7%. The subsequent loading of anticancer drug doxorubicin (Dox) creates a superior theranostic agent with pH- and heat-responsive drug release, leading to almost complete destruction of mouse cervical tumor under NIR laser irradiation. This development offers an attractive theranostic agent for in vivo chemo-photothermal synergistic therapy toward biomedical applications. Electronic supplementary information (ESI) available: The calculation of the photothermal conversion

  13. ZOT-derived peptide and chitosan functionalized nanocarrier for oral delivery of protein drug.

    PubMed

    Lee, Jong Hyun; Sahu, Abhishek; Choi, Won Il; Lee, Jae Young; Tae, Giyoong

    2016-10-01

    In this study, we developed a dual ligand functionalized pluronic-based nanocarrier (NC) for oral delivery of insulin. Chitosan and zonula occludins toxin (ZOT)-derived, tight junction opening peptide were conjugated to NC to increase the permeability of loaded insulin across the small intestine through the paracellular pathway. Surface functionalized NC, either by chitosan or peptide, could modulate the tight junction (TJ) integrity in contrast to no effect of unmodified NC, as evidenced by the change in transepithelial electrical resistance (TEER) and immunostaining of Claudin-4, a tight junction marker, in Caco-2 cell monolayer. On the other hand, dual ligand (chitosan and peptide) functionalized NC significantly further increased the permeation of insulin across Caco-2 cell monolayer. More importantly, insulin loaded, dual ligand functionalized NC could increase the plasma insulin level and efficiently regulate the glycemic response for a prolonged period of time (∼1 day) upon oral administration to diabetic rats, whereas delivery of insulin by single ligand functionalized NCs, either by chitosan or peptide, as well as by unmodified NC and free insulin, could not induce the effective regulation of the blood glucose level. The use of fluorescence dye labeled insulin (FITC-insulin) and Cy5.5 labeled NC revealed that both insulin and dual ligand functionalized NC were adequately penetrated across the whole intestine villi in contrast to limited adsorption of insulin and NC mainly onto the epithelial surface of the intestine for single ligand functionalized NCs. These results suggest that dual conjugation of ZOT-derived peptide and chitosan is a promising approach to functionalize the surface of nanocarrier for oral delivery of protein drugs. PMID:27380442

  14. Lyophilized phytosomal nanocarriers as platforms for enhanced diosmin delivery: optimization and ex vivo permeation.

    PubMed

    Freag, May S; Elnaggar, Yosra S R; Abdallah, Ossama Y

    2013-01-01

    Diosmin (DSN) is an outstanding phlebotonic flavonoid with a tolerable potential for the treatment of colon and hepatocellular carcinoma. Being highly insoluble, DSN bioavailability suffers from high inter-subject variation due to variable degrees of permeation. This work endeavored to develop novel DSN loaded phytosomes in order to improve drug dissolution and intestinal permeability. Three preparation methods (solvent evaporation, salting out, and lyophilization) were compared. Nanocarrier optimization encompassed different soybean phospholipid (SPC) types, different solvents, and different DSN:SPC molar ratios (1:1, 1:2, and 1:4). In vitro appraisal encompassed differential scanning calorimetry, infrared spectroscopy, particle size, zeta potential, polydispersity index, transmission electron microscopy, drug content, and in vitro stability. Comparative dissolution studies were performed under sink versus non-sink conditions. Ex vivo intestinal permeation studies were performed on rats utilizing noneverted sac technique and high-performance liquid chromatography analysis. The results revealed lyophilization as the optimum preparation technique using SPC and solvent mixture (Dimethyl sulphoxide:t-butylalchol) in a 1:2 ratio. Complex formation was contended by differential scanning calorimetry and infrared data. Optimal lyophilized phytosomal nanocarriers (LPNs) exhibited the lowest particle size (316 nm), adequate zeta-potential (-27 mV), and good in vitro stability. Well formed, discrete vesicles were revealed by transmission electron microscopy, drug content, and in vitro stability. Comparative dissolution studies were performed. LPNs demonstrated significant enhancement in DSN dissolution compared to crude drug, physical mixture, and generic and brand DSN products. Permeation studies revealed 80% DSN permeated from LPNs via oxygenated rat intestine compared to non-detectable amounts from suspension. In this study, LPNs (99% drug loading) could be successfully

  15. A Light-Driven Therapy of Pancreatic Adenocarcinoma Using Gold Nanorods-Based Nanocarriers for Co-Delivery of Doxorubicin and siRNA.

    PubMed

    Yin, Feng; Yang, Chengbin; Wang, Qianqian; Zeng, Shuwen; Hu, Rui; Lin, Guimiao; Tian, Jinglin; Hu, Siyi; Lan, Rong Feng; Yoon, Ho Sup; Lu, Fei; Wang, Kuan; Yong, Ken-Tye

    2015-01-01

    In this work, we report the engineering of polyelectrolyte polymers coated Gold nanorods (AuNRs)-based nanocarriers that are capable of co-delivering small interfering RNA (siRNA) and an anticancer drug doxorubicin (DOX) to Panc-1 cancer cells for combination of both chemo- and siRNA-mediated mutant K-Ras gene silencing therapy. Superior anticancer efficacy was observed through synergistic combination of promoted siRNA and DOX release upon irradiating the nanoplex formulation with 665 nm light. Our antitumor study shows that the synergistic effect of AuNRs nanoplex formulation with 665 nm light treatment is able to inhibit the in vivo tumor volume growth rate by 90%. The antitumor effect is contributed from the inactivation of K-Ras gene and thereby causing a profound synthesis (S) phase arrest in treated Panc-1 cells. Our study shows that the percentage of Panc-1 cells treated by nanoplex formulation with S phase is determined to be 35% and it is 17% much higher than that of Panc-1 cells without any treatments. The developed nanotherapy formulation here, that combines chemotherapy, RNA silencing and NIR window light-mediated therapy, will be seen to be the next natural step to be taken in the clinical research for improving the therapeutic outcomes of the pancreatic adenocarcinoma treatment. PMID:26000055

  16. Multifunctional Nanocarriers for diagnostics, drug delivery and targeted treatment across blood-brain barrier: perspectives on tracking and neuroimaging

    PubMed Central

    2010-01-01

    Nanotechnology has brought a variety of new possibilities into biological discovery and clinical practice. In particular, nano-scaled carriers have revolutionalized drug delivery, allowing for therapeutic agents to be selectively targeted on an organ, tissue and cell specific level, also minimizing exposure of healthy tissue to drugs. In this review we discuss and analyze three issues, which are considered to be at the core of nano-scaled drug delivery systems, namely functionalization of nanocarriers, delivery to target organs and in vivo imaging. The latest developments on highly specific conjugation strategies that are used to attach biomolecules to the surface of nanoparticles (NP) are first reviewed. Besides drug carrying capabilities, the functionalization of nanocarriers also facilitate their transport to primary target organs. We highlight the leading advantage of nanocarriers, i.e. their ability to cross the blood-brain barrier (BBB), a tightly packed layer of endothelial cells surrounding the brain that prevents high-molecular weight molecules from entering the brain. The BBB has several transport molecules such as growth factors, insulin and transferrin that can potentially increase the efficiency and kinetics of brain-targeting nanocarriers. Potential treatments for common neurological disorders, such as stroke, tumours and Alzheimer's, are therefore a much sought-after application of nanomedicine. Likewise any other drug delivery system, a number of parameters need to be registered once functionalized NPs are administered, for instance their efficiency in organ-selective targeting, bioaccumulation and excretion. Finally, direct in vivo imaging of nanomaterials is an exciting recent field that can provide real-time tracking of those nanocarriers. We review a range of systems suitable for in vivo imaging and monitoring of drug delivery, with an emphasis on most recently introduced molecular imaging modalities based on optical and hybrid contrast, such as

  17. Photocrosslinkable Gelatin Hydrogel for Epidermal Tissue Engineering.

    PubMed

    Zhao, Xin; Lang, Qi; Yildirimer, Lara; Lin, Zhi Yuan; Cui, Wenguo; Annabi, Nasim; Ng, Kee Woei; Dokmeci, Mehmet R; Ghaemmaghami, Amir M; Khademhosseini, Ali

    2016-01-01

    Natural hydrogels are promising scaffolds to engineer epidermis. Currently, natural hydrogels used to support epidermal regeneration are mainly collagen- or gelatin-based, which mimic the natural dermal extracellular matrix but often suffer from insufficient and uncontrollable mechanical and degradation properties. In this study, a photocrosslinkable gelatin (i.e., gelatin methacrylamide (GelMA)) with tunable mechanical, degradation, and biological properties is used to engineer the epidermis for skin tissue engineering applications. The results reveal that the mechanical and degradation properties of the developed hydrogels can be readily modified by varying the hydrogel concentration, with elastic and compressive moduli tuned from a few kPa to a few hundred kPa, and the degradation times varied from a few days to several months. Additionally, hydrogels of all concentrations displayed excellent cell viability (>90%) with increasing cell adhesion and proliferation corresponding to increases in hydrogel concentrations. Furthermore, the hydrogels are found to support keratinocyte growth, differentiation, and stratification into a reconstructed multilayered epidermis with adequate barrier functions. The robust and tunable properties of GelMA hydrogels suggest that the keratinocyte laden hydrogels can be used as epidermal substitutes, wound dressings, or substrates to construct various in vitro skin models. PMID:25880725

  18. Preparation and evaluation of poly(ethylene glycol)-poly(lactide) micelles as nanocarriers for oral delivery of cyclosporine a.

    PubMed

    Zhang, Yanhui; Li, Xinru; Zhou, Yanxia; Wang, Xiaoning; Fan, Yating; Huang, Yanqing; Liu, Yan

    2010-01-01

    A series of monomethoxy poly(ethylene glycol)-poly(lactide) (mPEG-PLA) diblock copolymers were designed according to polymer-drug compatibility and synthesized, and mPEG-PLA micelle was fabricated and used as a nanocarrier for solubilization and oral delivery of Cyclosporine A (CyA). CyA was efficiently encapsulated into the micelles with nanoscaled diameter ranged from 60 to 96 nm with a narrow size distribution. The favorable stabilities of CyA-loaded polymeric micelles were observed in simulated gastric and intestinal fluids. The in vitro drug release investigation demonstrated that drug release was retarded by polymeric micelles. The enhanced intestinal absorption of CyA-loaded polymeric micelles, which was comparable to the commercial formulation of CyA (Sandimmun Neoral®), was found. These suggested that polymeric micelles might be an effective nanocarrier for solubilization of poorly soluble CyA and further improving oral absorption of the drug. PMID:20671795

  19. Preparation and Evaluation of Poly(Ethylene Glycol)-Poly(Lactide) Micelles as Nanocarriers for Oral Delivery of Cyclosporine A

    NASA Astrophysics Data System (ADS)

    Zhang, Yanhui; Li, Xinru; Zhou, Yanxia; Wang, Xiaoning; Fan, Yating; Huang, Yanqing; Liu, Yan

    2010-06-01

    A series of monomethoxy poly(ethylene glycol)-poly(lactide) (mPEG-PLA) diblock copolymers were designed according to polymer-drug compatibility and synthesized, and mPEG-PLA micelle was fabricated and used as a nanocarrier for solubilization and oral delivery of Cyclosporine A (CyA). CyA was efficiently encapsulated into the micelles with nanoscaled diameter ranged from 60 to 96 nm with a narrow size distribution. The favorable stabilities of CyA-loaded polymeric micelles were observed in simulated gastric and intestinal fluids. The in vitro drug release investigation demonstrated that drug release was retarded by polymeric micelles. The enhanced intestinal absorption of CyA-loaded polymeric micelles, which was comparable to the commercial formulation of CyA (Sandimmun Neoral®), was found. These suggested that polymeric micelles might be an effective nanocarrier for solubilization of poorly soluble CyA and further improving oral absorption of the drug.

  20. Persistent Luminescent Nanocarrier as an Accurate Tracker in Vivo for Near Infrared-Remote Selectively Triggered Photothermal Therapy.

    PubMed

    Zheng, Bin; Chen, Hong-Bin; Zhao, Pei-Qi; Pan, Hui-Zhuo; Wu, Xiao-Li; Gong, Xiao-Qun; Wang, Han-Jie; Chang, Jin

    2016-08-24

    Optical imaging-guidance of indocyanine green (ICG) for photothermal therapy (PTT) has great latent capacity in cancer therapy. However, the conventional optical image-guidance mode has caused strong tissue autofluorescence of the living tissue, which leads to the accurate infrared light irradiation cannot be conducted. In this article, ICG and persistent luminescence phosphors (PLPs) coloaded mesoporous silica nanocarriers ((ICG+PLPs)@mSiO2) were first designed and prepared for persistent luminescent imaging-guided PTT. The (ICG+PLPs)@mSiO2 nanocarriers could significantly improve signal-to-noise ratio during luminescence imaging-guided PTT, making the PLP promising for improving the accuracy of the tumor site for photothermal therapy in vivo. This paper is likely to develop a new way for accurately regulating cancer cell death based on luminescence imaging-guided PTT selectively triggered by near-infrared (NIR)-remote. PMID:27491888

  1. Drug Delivery Nanocarriers from a Fully Degradable PEG-Conjugated Polyester with a Reduction-Responsive Backbone.

    PubMed

    Yameen, Basit; Vilos, Cristian; Choi, Won Il; Whyte, Andrew; Huang, Jining; Pollit, Lori; Farokhzad, Omid C

    2015-08-01

    The remarkably high intracellular concentration of reducing agents is an excellent endogenous stimulus for designing nanocarriers programmed for intracellular delivery of therapeutic agents. However, despite their excellent biodegradability profiles, aliphatic polyesters that are fully degradable in response to the intracellular reducing environment are rare. Herein, a reduction-responsive drug delivery nanocarrier derived from a linear polyester bearing disulfide bonds is reported. The reduction-responsive polyester is synthesized via a convenient polycondensation process. After conjugation of terminal carboxylic acid groups of polyester to polyethylene glycol (PEG), the resulting polymer self-assembles into nanoparticles that are capable of encapsulating dye and anticancer drug molecules. The reduction-responsive nanoparticles display a fast payload release rate in response to the intracellular reducing environment, which translates into superior anticancer activity towards PC-3 cells. PMID:26177931

  2. ATP-Responsive and Near-Infrared-Emissive Nanocarriers for Anticancer Drug Delivery and Real-Time Imaging

    PubMed Central

    Qian, Chenggen; Chen, Yulei; Zhu, Sha; Yu, Jicheng; Zhang, Lei; Feng, Peijian; Tang, Xin; Hu, Quanyin; Sun, Wujin; Lu, Yue; Xiao, Xuanzhong; Shen, Qun-Dong; Gu, Zhen

    2016-01-01

    Stimuli-responsive and imaging-guided drug delivery systems hold vast promise for enhancement of therapeutic efficacy. Here we report an adenosine-5'-triphosphate (ATP)-responsive and near-infrared (NIR)-emissive conjugated polymer-based nanocarrier for the controlled release of anticancer drugs and real-time imaging. We demonstrate that the conjugated polymeric nanocarriers functionalized with phenylboronic acid tags on surface as binding sites for ATP could be converted to the water-soluble conjugated polyelectrolytes in an ATP-rich environment, which promotes the disassembly of the drug carrier and subsequent release of the cargo. In vivo studies validate that this formulation exhibits promising capability for inhibition of tumor growth. We also evaluate the metabolism process by monitoring the fluorescence signal of the conjugated polymer through the in vivo NIR imaging. PMID:27217838

  3. ATP-Responsive and Near-Infrared-Emissive Nanocarriers for Anticancer Drug Delivery and Real-Time Imaging.

    PubMed

    Qian, Chenggen; Chen, Yulei; Zhu, Sha; Yu, Jicheng; Zhang, Lei; Feng, Peijian; Tang, Xin; Hu, Quanyin; Sun, Wujin; Lu, Yue; Xiao, Xuanzhong; Shen, Qun-Dong; Gu, Zhen

    2016-01-01

    Stimuli-responsive and imaging-guided drug delivery systems hold vast promise for enhancement of therapeutic efficacy. Here we report an adenosine-5'-triphosphate (ATP)-responsive and near-infrared (NIR)-emissive conjugated polymer-based nanocarrier for the controlled release of anticancer drugs and real-time imaging. We demonstrate that the conjugated polymeric nanocarriers functionalized with phenylboronic acid tags on surface as binding sites for ATP could be converted to the water-soluble conjugated polyelectrolytes in an ATP-rich environment, which promotes the disassembly of the drug carrier and subsequent release of the cargo. In vivo studies validate that this formulation exhibits promising capability for inhibition of tumor growth. We also evaluate the metabolism process by monitoring the fluorescence signal of the conjugated polymer through the in vivo NIR imaging. PMID:27217838

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

    NASA Astrophysics Data System (ADS)

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

    2014-07-01

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

  5. Affinity-controlled protein encapsulation into sub-30 nm telodendrimer nanocarriers by multivalent and synergistic interactions.

    PubMed

    Wang, Xu; Shi, Changying; Zhang, Li; Bodman, Alexa; Guo, Dandan; Wang, Lili; Hall, Walter A; Wilkens, Stephan; Luo, Juntao

    2016-09-01

    Novel nanocarriers are highly demanded for the delivery of heterogeneous protein therapeutics for disease treatments. Conventional nanoparticles for protein delivery are mostly based on the diffusion-limiting mechanisms, e.g., physical trapping and entanglement. We develop herein a novel linear-dendritic copolymer (named telodendrimer) nanocarrier for efficient protein delivery by affinitive coating. This affinity-controlled encapsulation strategy provides nanoformulations with a small particle size (<30 nm), superior loading capacity (>50% w/w) and maintained protein bioactivity. We integrate multivalent electrostatic and hydrophobic functionalities synergistically into the well-defined telodendrimer scaffold to fine-tune protein binding affinity and delivery properties. The ion strength and density of the charged groups as well as the structure of the hydrophobic segments are important and their combinations in telodendrimers are crucial for efficient protein encapsulation. We have conducted a series of studies to understand the mechanism and kinetic process of the protein loading and release, utilizing electrophoresis, isothermal titration calorimetry, Förster resonance energy transfer spectroscopy, bio-layer interferometry and computational methods. The optimized nanocarriers are able to deliver cell-impermeable therapeutic protein intracellularly to kill cancer cells efficiently. In vivo imaging studies revealed cargo proteins preferentially accumulate in subcutaneous tumors and retention of peptide therapeutics is improved in an orthotopic brain tumor, these properties are evidence of the improved pharmacokinetics and biodistributions of protein therapeutics delivered by telodendrimer nanoparticles. This study presents a bottom-up strategy to rationally design and fabricate versatile nanocarriers for encapsulation and delivery of proteins for numerous applications. PMID:27294543

  6. Preparation and tumor cell model based biobehavioral evaluation of the nanocarrier system using partially reduced graphene oxide functionalized by surfactant

    PubMed Central

    Wang, Yimin; Liu, Kunping; Luo, Zewei; Duan, Yixiang

    2015-01-01

    Background Currently, surfactant-functionalized nanomaterials are tending toward development of novel tumor-targeted drug carriers to overcome multidrug resistance in cancer therapy. Now, investigating the biocompatibility and uptake mechanism of specific drug delivery systems is a growing trend, but usually a troublesome issue, in simple pharmaceutical research. Methods We first reported the partially reduced graphene oxide modified with poly(sodium 4-styrenesulfonate) (PSS) as a nanocarrier system. Then, the nanocarrier was characterized by atomic force microscope, scanning electron microscope, high-resolution transmission electron microscope, ultraviolet–visible (UV-vis) spectroscopy, Fourier transform infrared spectroscopy, X-Ray powder diffraction, and Raman spectroscopy. Epirubicin (EPI) was attached to PSSG via π–π stacking, hydrogen bonding, and physical absorption to form conjugates of PSSG–EPI. The adsorption and desorption profiles, cytotoxicity coupled with drug accumulation, and uptake of PSSG and PSSG–EPI were evaluated. Finally, the subcellular behaviors, distribution, and biological fate of the drug delivery system were explored by confocal laser scanning microscope using direct fluorescence colocalization imaging and transmission electron microscopy. Results The partially reduced graphene oxide sheets functionalized by surfactant exhibit good dispersibility. Moreover, due to much less carboxyl groups retained on the edge of PSSG sheets, the nanocarriers exhibit biocompatibility in vitro. The obtained PSSG shows a high drug-loading capacity of 2.22 mg/mg. The complexes of PSSG–EPI can be transferred to lysosomes in 2 hours through endocytosis, then the drug is released in the cytoplasm in 8 hours, and ultimately EPI is delivered into cell nucleus to exhibit medicinal effects in 1 day. Conclusion The comprehensive exploration of the biological uptake mechanism of functional graphene-mediated tumor cell targeting model provides a typical

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

    PubMed

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

    2016-01-01

    During the last years we have seen an increasing number of reports describing new properties and potential applications of cationic polymers and derived nanostructures. This review gives a summary of their applications in drug delivery, the preparation methods for nano and microstructures and will attempt to give a glimpse on how their structure, chemical composition and properties may be affected or modulated as to make them suitable for an intended application as drug delivery nanocarriers. The compositional complexity with the existence of several reacting groups makes cationic nanostructures critically sensitive to the contribution of thermodynamic and kinetic parameters in the determination of the type and stability of a particular structure and its ability to respond to changes in environmental conditions in the right time frame. Curiously, and contrarily to what could be expected, despite the fact that cationic polymers can form strong electrostatic interactions the contribution of the entropic component has been often found to be very important for their association with negatively charged supramolecular structures. Some general considerations indicate that when considering a complex multimolecular system like a nanocarrier containing an active ingredient it is frequently possible to find conditions under which enthalpic and entropic contributions are compensated leading to stable structures with a marginal thermodynamic stability (free energy change close to zero) which make them able to respond relatively fast to changes in the environmental conditions and therefore suitable for the design of smart drug delivery systems. Like with other nanocarriers, it should always be kept in mind that the properties of cationic nanocarriers will depend not only on their chemical composition but also on the properties of the structures formed by them. PMID:26845328

  8. Targeted Delivery of Docetaxel by Use of Transferrin/Poly(allylamine hydrochloride)-functionalized Graphene Oxide Nanocarrier.

    PubMed

    Nasrollahi, Fatemeh; Varshosaz, Jaleh; Khodadadi, Abbas Ali; Lim, Sierin; Jahanian-Najafabadi, Ali

    2016-06-01

    The exceptional chemical and physical properties of graphene oxide (GO) make it an attractive nanomaterial for biomedical applications, particularly in drug delivery. In this work we synthesized a novel, GO-based nanocarrier for the delivery of docetaxel (DTX), a potent hydrophobic chemotherapy drug. The GO was functionalized with transferrin (Tf)-poly(allylamine hydrochloride) (PAH), which provided targeted and specific accumulation to extracellular Tf receptors and stabilized GO in physiological solutions. Tf was conjugated to PAH via amide covalent linkages, and Tf-PAH coated the surface of DTX-loaded GO through electrostatic interactions. The morphology and structure of the resulting nanostructure, along with its surface modifications, were verified by use of Fourier transform infrared (FT-IR) and UV-vis spectroscopy, atomic force microscopy (AFM), and scanning electron microscopy (SEM). DTX was loaded at a relatively high loading capacity of 37% and released in a pH-dependent and sustained manner under physiological conditions. The targeting efficiency and cytotoxicity of this drug delivery system were evaluated on MCF-7 breast cancer cells. Improved efficacy of targeted DTX-loaded nanocarrier was observed compared to nontargeted carrier and free DTX, especially at high drug concentrations. The Tf-PAH-functionalized GO nanocarrier is a promising candidate for targeted delivery and controlled release of DTX. PMID:27158834

  9. Dual-targeting nanocarrier system based on thermosensitive liposomes and gold nanorods for cancer thermo-chemotherapy.

    PubMed

    Yu, Meng; Guo, Fang; Tan, Fengping; Li, Nan

    2015-10-10

    The primary challenge of cancer therapy was the failure of most chemotherapeutics to accumulate in the tumors, additionally causing serious systemic side effects. We designed a tumor-targeting accumulated and locally triggered-release nanocarrier system to increase the intratumoral drug concentration and thus the efficacy of chemotherapy, based on gold nanorods (GNRs) and thermosensitive liposomes (TSLs). PEGylated GNRs could not only make nanocarriers to co-accumulate in tumors depending on enhanced permeability and retention (EPR) effect, but also generated heat locally under near-infrared (NIR) stimulation. CO2 bubbles were generated by the encapsulated ammonium bicarbonate (ABC) under hyperthermia, thus the co-encapsulated drug was released and local drug concentration was increased along with the disintegration of liposomal membrane. On the other hand, this dual-targeting system prevented the drug leakage in blood circulation or other organs while facilitated most of the active agents delivered to tumors. In vitro and in vivo experiments revealed high cytotoxicity and good affinity of HTSL to MDA-MB-435 cells when used synergistically with GNRs, but low toxicity to normal cells at the same condition. When combined with thermotherapy, the smart nanocarrier system held significant promise for future cancer treatment for their markedly improved therapeutic efficacy and decreased systemic toxicity. PMID:26256259

  10. Effective co-delivery of doxorubicin and dasatinib using a PEG-Fmoc nanocarrier for combination cancer chemotherapy.

    PubMed

    Zhang, Peng; Li, Jiang; Ghazwani, Mohammed; Zhao, Wenchen; Huang, Yixian; Zhang, Xiaolan; Venkataramanan, Raman; Li, Song

    2015-10-01

    A simple PEGylated peptidic nanocarrier, PEG5000-lysyl-(α-Fmoc-ε-Cbz-lysine)2 (PLFCL), was developed for effective co-delivery of doxorubicin (DOX) and dasatinib (DAS) for combination chemotherapy. Significant synergy of DOX and DAS in inhibition of cancer cell proliferation was demonstrated in various types of cancer cells, including breast, prostate, and colon cancers. Co-encapsulation of the two agents was facilitated by incorporation of 9-Fluorenylmethoxycarbonyl (Fmoc) and carboxybenzyl (Cbz) groups into a nanocarrier for effective carrier-drug interactions. Spherical nanomicelles with a small size of ∼30 nm were self-assembled by PLFCL. Strong carrier/drug intermolecular π-π stacking was demonstrated in fluorescence quenching and UV absorption. Fluorescence study showed more effective accumulation of DOX in nuclei of cancer cells following treatment with DOX&DAS/PLFCL in comparison with cells treated with DOX/PLFCL. DOX&DAS/PLFCL micelles were also more effective than other treatments in inhibiting the proliferation and migration of cultured cancer cells. Finally, a superior anti-tumor activity was demonstrated with DOX&DAS/PLFCL. A tumor growth inhibition rate of 95% was achieved at a respective dose of 5 mg/kg for DOX and DAS in a murine breast cancer model. Our nanocarrier may represent a simple and effective system that could facilitate clinical translation of this promising multi-agent regimen in combination chemotherapy. PMID:26210177