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WO2009097439A1 - Nano-dispositifs possédant des valves permettant la libération contrôlée de molécules - Google Patents

Nano-dispositifs possédant des valves permettant la libération contrôlée de molécules Download PDF

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Publication number
WO2009097439A1
WO2009097439A1 PCT/US2009/032451 US2009032451W WO2009097439A1 WO 2009097439 A1 WO2009097439 A1 WO 2009097439A1 US 2009032451 W US2009032451 W US 2009032451W WO 2009097439 A1 WO2009097439 A1 WO 2009097439A1
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Prior art keywords
nanodevice
nanoparticles
chem
valve assembly
nanoparticle
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PCT/US2009/032451
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English (en)
Inventor
Jeffrey I. Zink
Jie Lu
Fuyuhiko Tamanoi
Sarah Angelos
Fraser Stoddart
Qiaolin Chen
Andre Nel
Tian Xia
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The Regents Of The University Of California
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Publication of WO2009097439A1 publication Critical patent/WO2009097439A1/fr
Priority to US12/841,331 priority Critical patent/US20100310465A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/51—Nanocapsules; Nanoparticles
    • A61K9/5107—Excipients; Inactive ingredients
    • A61K9/5115—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6949—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0097—Micromachined devices; Microelectromechanical systems [MEMS]; Devices obtained by lithographic treatment of silicon; Devices comprising chips
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/51—Nanocapsules; Nanoparticles
    • A61K9/5192—Processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/40—Cyclodextrins; Derivatives thereof

Definitions

  • the current invention relates to nano-devices, and more specifically to nano- nano-devices that have valves for controlled release of molecules contained therein.
  • Control of molecular transport in, through, and out of mesopores has important potential applications in nanoscience including fluidics and drug delivery.
  • Surfactant-templated silica (Kresge, C. T.; Leonowicz, M. E.; Roth, W. J.; Vartuli, J. C; Beck, J. S. Nature 1992, 359, 710-712) is a versatile material in which ordered arrays of mesopores can be easily synthesized, providing a convenient platform for attaching molecules that undergo large amplitude motions to control transport.
  • Mesostructured silica is transparent (for photocontrol and spectroscopic monitoring), and can be fabricated into useful morphologies (thin films (Lu, Y.
  • nanovalves in therapeutic applications, for example, it is imperative that they not only employ biocompatible components but that they also operate under physiological conditions.
  • a recognition and binding motif which operates in aqueous media has to be identified, tried and tested. Consequently, there remains a need for improved nano-devices.
  • a nanodevice has a containment vessel, defining a storage chamber therein and defining at least one port to provide transfer of matter to or from the storage chamber, and a valve assembly attached to the containment vessel.
  • the valve assembly is operable in an aqueous environment.
  • the nanodevice comprises biocompatible materials and has a maximum dimension of less than about 1 ⁇ m and greater than about 50 nm.
  • a composition of matter according to some embodiments of the current invention has a plurality of nanoparticles, each defining a storage chamber therein, and a guest material contained within the storage chambers defined by the nanoparticles, the guest material being substantially chemically non-reactive with the nanoparticles.
  • Each nanoparticle of the plurality of nanoparticles has a valve assembly to allow the guest material contained within the storage chambers to be selectively released, and each nanoparticle of the plurality of nanoparticles comprises biocompatible materials in a composition thereof and has a maximum dimension of less than about 1 ⁇ m and greater than about 50 run.
  • a method of administering at least one of a biologically active substance, a therapeutic substance, a neutraceutical substance, a cosmetic substance or a diagnostic substance includes administering a composition to at least one of a person, an animal, a plant, or an organism, the composition comprising nanoparticles therein.
  • the nanoparticles contain the at least one of the biologically active substance, therapeutic substance, neutraceutical substance, cosmetic substance or diagnostic substance therein
  • the method also includes selectively opening a valve in each of the nanoparticles to allow the at least one of the biologically active substance, therapeutic substance, neutraceutical substance, cosmetic substance or diagnostic substance to escape from the nanoparticles.
  • FIGS 1A-1C provide schematic illustrations of a nano-device and methods of production/operation according to an embodiment of the current invention.
  • the alkyne-functionalized mesoporous silica nanoparticles MCM-41 are loaded (a— >b) with Rhodamine B (RhB) molecules, and capped (a ⁇ b) with CB[6] during the CB[6]-catalyzed alkyne-azide 1,3-dipolar cycloadditions, followed by washing away the excess of substrates.
  • RhB molecules are released (b— >c) by switching off the ion-dipole interactions between the CB[6] rings and the bisammonium stalks upon raising the pH.
  • Figure 2 is schematic illustration to help explain additional embodiments of the current invention.
  • Figure 3 shows (a) The XRD pattern and (b) SEM image of mesoporous silica nanoparticles ⁇ 3 c CB[6] ⁇ produced according to an embodiment of the current invention.
  • Figures 4A and 4B illustrate synthetic routes to mesoporous silica nanoparticles functionalized with CB [6] / dialkylammonium pseudorotaxanes according to some embdiments of the current invention, i) and iv) propargyl bromide, MeOH, 50 0 C, overnight; ii) and v) 0.5 mM RhB, H 2 O, RT, 5 h; then CB[6], 2N HCl, RT, 3 d; iii) NaNH 2 , PhMe, heat under reflux, 12 h.
  • Figures 5A and 5B provide data taken for the release of the RhB guest molecules monitored by following the luminescence intensity of the solution of (a) nanoparticles with longer linkers ⁇ 3 c CB[6] ⁇ and (b) nanoparticles with shorter linkers ⁇ 6 c CB[6] ⁇ (upper trace) according to two embodiments of the current invention. Control experiments without changing pH (lower trace), with respect to time were also performed. Whereas (a) exhibits substantial leakage, as indicated by the premature rise in luminescence intensity, (b) shows no leakage.
  • FIG. 6 is a schematic representation of a cucurbit[6]uril-based pH-driven molecular nanovalve system according to an embodiment of the current invention in which the cucurbituril at the pore openings gate the release of material (e.g., drug molecules), i) PhN(Boc)(CH 2 ) 6 N(Boc)(CH 2 ) 4 NH 2 , Methanol, reflux; Trifluoroacetic acid; adjust pH to larger than 6.73; ii) loading drug / dye; capping with cucurbit[6]uril; iii) adjust pH to acidic less than 6.73 to release the trapped molecules.
  • material e.g., drug molecules
  • FIG. 1A is a schematic illustration of a nanodevice 100 according to an embodiment of the current invention.
  • the nanodevice 100 has a containment vessel 102 defining a storage chamber 104 therein and defining at least one port 106 to provide access for the transfer of material 108 into and/or out of the storage chamber 104.
  • the containment vessel 102 can be a mesoporous silica nanopaiticle in some embodiments of the current invention.
  • the material 108 can be molecules which are sometimes also referred to as guest molecules herein.
  • the Rhodamine B molecules illustrated schematically in Figures 1 A-IC are only one example of a very wide range of possible materials 108 that can be selected based on the desired application.
  • the material 108 is not limited to this example.
  • the material 108 does not always have to be in the form of molecules in some embodiments of the current invention.
  • the material 108 is also referred to as cargo herein since it can be loaded into the nanodevice 100.
  • the nanodevice 100 also has a valve assembly 110 attached to the containment vessel 102.
  • the valve assembly 110 has a valve 112 arranged proximate the at least one port 106 and has a structure suitable to substantially prevent material 108 after being loaded into the storage chamber 104 from being released while the valve 112 is arranged in a blocking configuration.
  • the valve assembly 110 is responsive to a change in pH such that the valve 112 moves in the presence of the change in pH to allow the material 108 to be released from the storage chamber 104.
  • the nanodevice 100 has a maximum dimension of less than about 1 ⁇ m and greater than about 50 nm in some embodiments.
  • the nanodevice 100 has a maximum dimension of less than about 400 nm and greater than about 50 nm.
  • the nanodevice 100 is greater than about 400 nm, it becomes too large to enter into biological cells.
  • the nanodevice 100 is less than about 50 nm, it becomes less able to contain a useful number of molecules therein.
  • the nanodevices are less than about 300 nm, they become more useful in some applications to biological systems.
  • nanodevices having a maximum dimension in the range of about 50 nm to about 150 nm are suitable.
  • the containment vessel can be, but is not limited to, a mesoporous silica nanoparticle according to some embodiments of the current invention.
  • the material or molecules of interest to be stored in and released from the containment vessels 102 can include, but are not limited to, biologically active substances.
  • biologically active substance as used herein is intended to include all compositions of matter that can cause a desired effect on biological material or a biological system and may include in situ and in vivo biological materials and systems.
  • the biologically active substance may be selected from such substances that have molecular sizes such that they can be loaded into the nanodevices, and can also be selected from such substances that don't react with the nanodevices.
  • a biological system may include a person, animal or plant, for example.
  • Bioly active substances may include, but are not limited to, the following:
  • Small molecule drugs for anticancer treatment such as camptothecin, paclitaxel and doxorubicin;
  • Ophthalmic drugs such as flurbiprofen, levobbunolol and neomycin
  • Nucleic acid reagents such as siRNA and DNAzymes
  • Small molecule drugs for immune suppression such as rapamycin, FK506, cyclosporine;
  • any pharmacological compound that can fit into the nanodevice e.g., analgesics, NSAIDS, steroids, hormones, anti-epileptics, anti-arrythmics, anti-hypentensives, antibiotics, antiviral agents, anticoagulants, platelet drugs, cardiostimulants, cholesterol lowering agents, etc.
  • Molecules of interest can also include imaging and/or tracking substances.
  • Imaging and/or tracking substances may include, but are not limited to, dye molecules such as propidium iodide, fluorescein, rhodamine, green fluorescent protein and derivatives thereof.
  • Figure 2 is a schematic illustration to facilitate the explanation of additional embodiments of the current invention.
  • Figure 2 does not show storage chambers, such as a plurality of pores of a mesoporous silica nanoparticle, and does not show valve assemblies.
  • the nanodevices can include a plurality of anionic molecules attached to the surface of the nanodevice as is illustrated schematically in Figure 2.
  • the anionic molecules can be phosphonate moieties attached to the outer surface of the nanodevice to effectively provide a phosphonate coating on the nanodevice.
  • the anionic molecules can be trihydroxysilylpropyl methylphosphonate molecules according to an embodiment of the current invention.
  • This phosphonate coating can provide a negative zeta potential that is responsible for electrostatic repulsion to keep such submicron structures dispersed in an aqueous tissue culture medium, for example.
  • This dispersion can also be important for keeping the particle size limited to a size scale that allows endocytic uptake (i.e., hinders clumping).
  • the negative zeta potential may play a role in the formation of a protein corona on the particle surface that can further assist cellular uptake in some applications. It is possible that this could include molecules such as albumin, transferrin or other serum proteins that could participate in receptor-mediated uptake.
  • the nanodevice 100 can also be functionalized with molecules in addition to anionic molecules according to some embodiments of the current invention.
  • a plurality of folate ligands can be attached to the outer surface of the containment vessel 102 according to some embodiments of the current invention, as is illustrated schematically in Figure 2 (valve assemblies are not shown for clarity).
  • the nanodevice 100 can also include fluorescent molecules contained in or attached to the containment vessel 102.
  • fluorescent molecules may be attached inside the pores of mesoporous silica nanoparticles according to some embodiments of the current invention.
  • the fluorescent molecules can be an amine-reactive fluorescent dye attached by being conjugated with an amine-functionalized silane according to some embodiments of the current invention.
  • some fluorescent molecules without limitation, can include fluorescein isothiocyanate, NHS-fluorescein, rhodamine B isothiocyanate, tetramethylrhodamine B isothiocyanate, and/or Cy5.5 NHS ester.
  • the nanodevices 100 may further comprise one or more nanoparticle of magnetic material formed within the containment vessel 102, as is illustrated schematically in Figure 2 for one particular embodiment.
  • the nanoparticles of magnetic material can be iron oxide nanoparticles according to an embodiment of the current invention.
  • the broad concepts of the current invention are not limited to only iron oxide materials for the magnetic nanoparticles.
  • Such nanoparticles of magnetic material incorporated in the submicron structures can permit them to be tracked by magnetic resonance imaging (MRI) systems and/or manipulated magnetically, for example.
  • MRI magnetic resonance imaging
  • the nanodevices 100 may further comprise one or more nanoparticle of a material that is optically dense to x-rays.
  • gold nanoparticles may be formed within the containment vessel 102 of the nanodevice 100 according to some embodiments of the current invention.
  • CB[6] cucurbit[6]uril
  • CB[6] a pumpkin-shaped polymacrocycle with D ⁇ h symmetry consisting of six glycouril units strapped together by pairs of bridging methylene groups between nitrogen atoms ((a) J. Lagona, P. Mukhopadhyay, S. Chakrabarti, L. Isaacs, Angew. Chem. 2005, 117, 4922 ⁇ 949; Angew. Chem. Int. Ed.
  • CB[6] Another important characteristic of CB[6] is its ability (a) W. L. Mock, T. A. Irra, J. P. Wepsiec, T. L.
  • the silica supports employed were ⁇ 400 run diameter spherical particles which contain ordered 2D hexagonal arrays of tubular pores ( ⁇ 2 nm pore diameters with ⁇ 4 nm lattice spacing) prepared using a base-catalyzed sol-gel method (a) S. Huh, J. W. Wiench, J.-C. Yoo, M. Pruski, V. S.-Y. Lin, Chem. Mater. 2003, 15, 4247 ⁇ 256; b) M. Grun, I. Laner, K. K. Unger, Adv. Mater. 1997, 9, 254-257; c) Y. Lu, R. Ganguli, C A. Drewien, M. T. Anderson, C. J.
  • FIG. 4A This system was designed ( Figure 4A) such that the valve assembly components can be assembled in a stepwise, divergent manner from the nanoparticle surface outwards according to an embodiment of the current invention.
  • the nanoparticles were heated under reflux in an aminopropyl-triethoxysilane (APTES) solution, resulting in the amino-modif ⁇ ed nanoparticles 1.
  • APTES aminopropyl-triethoxysilane
  • the empty nanopores in 2 were loaded with fluorescent guest molecules by soaking the nanoparticles in a 0.5 mM solution of Rhodamine B (RhB) for 5 h.
  • RhB Rhodamine B
  • the preparation of the valve systems was completed by means of an interfacial CB[6]-catalyzed 1,3- dipolar cycloaddition of the silica-supported alkyne function and 2-azidoethylamine to yield CB[6] / 1,3-disubstituted triazole [2]pseudorotaxanes ⁇ 3 cz CB[6] ⁇ spread all over the silica surface.
  • RhB RhB-capped nanoparticles were washed extensively with MeOH and H 2 O to remove adsorbed molecules from the surface. A portion of the washed nanoparticles (-15 mg) was placed in the bottom corner of a cuvette, and H 2 O (12 mL) was added carefully. A 10 mW, 514 nm probe beam, directed into the water above the nanoparticles, was used to excite the dye molecules as they are released from the nanoparticles. The emission spectrum of RhB was recorded as a function of time at 1 -second intervals.
  • valve systems were opened by adjusting the pH of the solution to 10 through the addition of 2M NaOH. Plots of the dissolved dye intensities as functions of time - the release profiles shown in Figure 5 - indicate an increase in the amount of dye released upon base activation, demonstrating that the valve systems do indeed open at high pH values.
  • valve assembly activation includes (i) the size of the valve assembly components, (ii) the positioning of the valve systems relative to the orifices of the nanopores and (iii) the length of the linker.
  • the outer diameter of the CB[6] ring (a) J. Lagona, P. Mukhopadhyay, S. Chakrabarti, L. Isaacs, Angew. Chem. 2005, 117, 4922- 4949; Angew. Chem. Int. Ed.
  • CMTES chloromethyl-triethoxysilane
  • the use of the shorter linker curtails the length of the stalk of the pseudorotaxane in ⁇ 6 c CB[6] ⁇ such that the CB[6] ring is positioned ⁇ 0.2 nm closer to the surface of the silica nanoparticle. This subtle change in linker length tightens up the valve systems sufficiently to prevent leakage and the release profile illustrated in Figure 5B is observed.
  • a concern regarding the operation of these valve systems is the stability of the silica supports under the high pH conditions required for the valve assembly to function.
  • Activation of the valve systems relies on deprotonation of the primary alkylammonium and secondary dialkylammonium centers (p ⁇ T a ⁇ 10) so as to disrupt the ion-dipole interactions responsible for binding of the CB[6] rings.
  • base NaOH
  • SEM images and X-ray diffraction patterns of the functionalized nanoparticles were compared before and after exposure to base. No noticeable differences in either the nanoparticle morphology or mesostructure were observed, indicating that the structure of the nanoparticle supports is preserved during the controlled release process.
  • valve systems based on CB [6] rings as the gatekeepers can play a significant role in the future of functionalized mesoporous silica nanoparticles for biotechnological and medical applications
  • J. Lu M. Liong, J. I. Zink, F.
  • CTAB cetyltrimethyl-ammonium bromide
  • the solvent-extracted nanoparticles were collected by vacuum filtration and washed thoroughly with MeOH.
  • Amino-modification of the silica surface was performed by suspending the nanoparticles (100 mg) in a solution of 3- aminopropyltriethoxy-silane (APTES) (1 mM) in dry PhMe (10 mL) and heating them under reflux for 24 h.
  • the nanoparticles were collected by filtration, washed thoroughly with PhMe, and dried under vacuum.
  • APTES 3- aminopropyltriethoxy-silane
  • [0039] 2 Refluxing aminopropyl-modified MCM-41 nanoparticles 1 in a MeOH solution of propargyl bromide for 24 h under N 2 (1 atm) afforded the alkyne-modif ⁇ ed MCM-41, resulting in silica nanoparticles 2 after washing them extensively with MeOH and drying them under vacuum.
  • the nanoparticles were characterized by means of FTIR, XRD, SEM, and DLS.
  • CMTES chloromethyl- triethoxysilane
  • Nanoparticles 5 were first modified with propargyl bromide by heating under reflux in MeOH under N 2 for 24 h to obtain the alkyne-terminated silica nanoparticles. Loading with RhB and completion of the valve assembly synthesis was achieved as described for valve assembly ⁇ 3 c CB [6] ⁇ . They were characterized by means of FT-IR, XRD and SEM.
  • a bistable CB[6]/triamine pseudorotaxane-based nanodevice having a valve assembly can be operated under mildly acidic conditions (Figure 6).
  • the important feature of the triamine thread functionalized onto the silica surface is that the pair of nitrogen atoms not connected directly to the benzene ring ought to be 10 6 -fold more basic than the one which is, so the pH changes will result in changes in the protonation state of the aniline N atom, which provides the possibility of the relocation of CB[6] host molecule.
  • CB[6] will move to the protonated diaminohexane site forming a more stable complex than with diprotonated diaminobutane, thus open the pores and release the drug/dye molecules trapped in the pores. This process is reversible due to the relocation of CB [6] when the pH is changed back to 6.73.

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Abstract

L'invention porte sur un nano-dispositif incluant un récipient de confinement définissant une chambre de stockage à l'intérieur dudit récipient et définissant au moins un port permettant le transfert de matière vers ladite chambre de stockage ou à partir de celle-ci, et incluant également un ensemble de valves fixé audit récipient de confinement. L'ensemble de valves est conçu pour fonctionner en milieu aqueux. Le nano-dispositif contient des matériaux biocompatibles et présente une dimension maximale inférieure à 1 µm environ et supérieure à 50 nm environ.
PCT/US2009/032451 2008-01-23 2009-01-29 Nano-dispositifs possédant des valves permettant la libération contrôlée de molécules WO2009097439A1 (fr)

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US12/841,331 US20100310465A1 (en) 2008-01-23 2010-07-22 Nano-devices having releasable seals for controlled release of molecules

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Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20130046274A1 (en) * 2011-07-14 2013-02-21 The Regents Of The University Of California Method of controlled delivery using sub-micron-scale machines
WO2013095736A3 (fr) * 2011-09-27 2014-01-23 The Methodist Hospital Research Institute Nanoassemblage d'or-en-silicium pour une thérapie thermique et procédés d'utilisation
CN104447768A (zh) * 2013-09-23 2015-03-25 贵州大学 七元瓜环[3]轮烷及其制备方法和应用
US9042765B2 (en) 2012-01-16 2015-05-26 Samsung Electronics Co., Ltd. Image forming apparatus with improved heat transmission
CN105983390A (zh) * 2015-01-30 2016-10-05 南京理工大学 一种pH刺激大环可逆移动的智能纳米容器及其制备方法
US9993437B2 (en) 2007-12-06 2018-06-12 The Regents Of The University Of California Mesoporous silica nanoparticles for biomedical applications
US10343903B2 (en) 2010-07-13 2019-07-09 The Regents Of The University Of California Cationic polymer coated mesoporous silica nanoparticles and uses thereof
CN114455776A (zh) * 2021-12-21 2022-05-10 中煤科工集团杭州研究院有限公司 一种基于生物脱氮的不锈钢酸洗废水处理方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6929636B1 (en) * 2000-11-08 2005-08-16 Hewlett-Packard Development Company, L.P. Internal drug dispenser capsule medical device
US20060154069A1 (en) * 2003-07-22 2006-07-13 Lin Victor S Capped mesoporous silicates

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6929636B1 (en) * 2000-11-08 2005-08-16 Hewlett-Packard Development Company, L.P. Internal drug dispenser capsule medical device
US20060154069A1 (en) * 2003-07-22 2006-07-13 Lin Victor S Capped mesoporous silicates

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9993437B2 (en) 2007-12-06 2018-06-12 The Regents Of The University Of California Mesoporous silica nanoparticles for biomedical applications
US10668024B2 (en) 2007-12-06 2020-06-02 The Regents Of The University Of California Mesoporous silica nanoparticles for biomedical applications
US10343903B2 (en) 2010-07-13 2019-07-09 The Regents Of The University Of California Cationic polymer coated mesoporous silica nanoparticles and uses thereof
US20130046274A1 (en) * 2011-07-14 2013-02-21 The Regents Of The University Of California Method of controlled delivery using sub-micron-scale machines
US10220004B2 (en) 2011-07-14 2019-03-05 The Regents Of The University Of California Method of controlled delivery using sub-micron-scale machines
WO2013095736A3 (fr) * 2011-09-27 2014-01-23 The Methodist Hospital Research Institute Nanoassemblage d'or-en-silicium pour une thérapie thermique et procédés d'utilisation
US9042765B2 (en) 2012-01-16 2015-05-26 Samsung Electronics Co., Ltd. Image forming apparatus with improved heat transmission
CN104447768A (zh) * 2013-09-23 2015-03-25 贵州大学 七元瓜环[3]轮烷及其制备方法和应用
CN105983390A (zh) * 2015-01-30 2016-10-05 南京理工大学 一种pH刺激大环可逆移动的智能纳米容器及其制备方法
CN105983390B (zh) * 2015-01-30 2018-05-01 南京理工大学 一种pH刺激大环可逆移动的智能纳米容器及其制备方法
CN114455776A (zh) * 2021-12-21 2022-05-10 中煤科工集团杭州研究院有限公司 一种基于生物脱氮的不锈钢酸洗废水处理方法
CN114455776B (zh) * 2021-12-21 2022-12-06 中煤科工集团杭州研究院有限公司 一种基于生物脱氮的不锈钢酸洗废水处理方法

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