Filament Formation
www.freepatentsonline.com/7195780.htmlPreferred nanotubes are those comprising silica or polymers. Silica nanotubes can be prepared using sol-gel template synthesis as described in Lakshmi, B. B.; Patrissi, C. J.; Martin, C. R., “Sol-Gel Template Synthesis of Semiconductor Oxide Micro- and Nanostructures,” Chem. Mater., 1997, 9, 2544–2550; Lakshmi, B. B.; Dorhout, P. K.; Martin, C. R. “Sol-Gel Template Synthesis of Semiconductor Nanostructures,” Chem. Mater., 1997, 9, 857–862, the contents of which are incorporated by this reference. Here the template membrane is immersed into a standard tetraethylorthosilicate sol so that the sol fills the pores. After the desired immersion time, the membrane is removed, dried in air and then cured at 150° C. This yields silica nanotubes lining the pore walls of the membrane plus silica surface films on both faces of the membrane.
The preferred dimensions of the nanotube depend on the intended application. When the nanotube is intended for in-vivo use, and particularly when the nanotube is to be
injected into the blood stream, the maximum dimension of the nanotube is preferably less than 500 nm.
A red blood cell is about 7000 nm in diameter, which corresponds to the diameter of the smallest capillaries in the human body. If the nanostructure complex has suitable surface property characteristics (surface charge and hydrophilicity/hydrophobicity balance) and has a dimension typically less than 10 nm, preferably 5 nm, it may be directly excreted from the body by the kidneys. On the other hand, if the nanostructure is larger and biodegradable, it won't be directly eliminated from the body (e.g., kidneys), but rather will be degraded into its smaller components, which in turn, are eliminated via the liver, kidney, bile, etc.
Polymer nanotubes can be prepared from many substances that are composed of monomer units. “Monomer units” are the individual moieties that are repeated to form “polymers”. Multiple monomer units are covalently attached when in the form of a backbone of a polymer.
Preferred polymers include polystyrene, polyorganosiloxane, poly(methyl methacrylate), polystyrene, polylactic acids, and other biodegradable polymers, acrylic latexes, polyorganosiloxane, cellulose, polyethylene, poly(vinyl chloride), poly(ethyl methacrylate), poly(tetrafluoroethylene), poly(4-iodostyrene/divinylbenzene), poly(4-vinylpyridine/divinylbenzene), poly(styrene/divinyl benzene), crosslinked melamine particles, phenolic polymer colloids, polyamide 6/6, natural rubber, naturally occurring biopolymers such as algenates, and collagen, or mixtures thereof.
When the nanotubes are to be introduced into an living organism, for example, when used as a vehicle for delivery of a bioactive material, biodegradable polymers and biocompatible polymers are especially preferred. A “biodegradable” substance is a substance that can be broken down by the action of living organisms. Examples of useful biodegradable polymers include polyesters, such as poly(caprolactone), poly(glycolic acid), poly(lactic acid), and poly(hydroxybutryate); polyanhydrides, such as poly(adipic anhydride) and poly(maleic anhydride); polydioxanone; polyamines; polyamides; polyurethanes; polyesteramides; polyorthoesters; polyacetals; polyketals; polycarbonates; polyorthocarbonates; polyphosphazenes; poly(malic acid); poly(amino acids); polyvinylpyrrolidone; poly(methyl vinyl ether); poly(alkylene oxalate); poly(alkylene succinate); polyhydroxycellulose; chitin; chitosan; and copolymers and mixtures thereof.
Examples of drugs which
may be delivered by nanotubes include, but are not limited to, prochlorperzine edisylate, ferrous sulfate, aminocaproic acid, mecamylamine hydrochloride, procainamide hydrochloride, amphetamine sulfate, methamphetamine hydrochloride, benzamphetamine hydrochloride, isoproterenol sulfate, phenmetrazine hydrochloride, bethanechol chloride, methacholine chloride, pilocarpine hydrochloride, atropine sulfate, scopolamine bromide, isopropamide iodide, tridihexethyl chloride, phenformin hydrochloride, methylphenidate hydrochloride, theophylline cholinate, cephalexin hydrochloride, diphenidol, meclizine hydrochloride, prochlorperazine maleate, phenoxybenzamine, thiethylperzine maleate, anisindone, diphenadione erythrityl tetranitrate, digoxin, isoflurophate, acetazolamide, methazolamide, bendroflumethiazide, chloropromaide, tolazamide, chlormadinone acetate, phenaglycodol, allopurinol, aluminum aspirin, methotrexate, acetyl sulfisoxazole, erythromycin, hydrocortisone, hydrocorticosterone acetate, cortisone acetate, dexamethasone and its derivatives such as betamethasone, triamcinolone, methyltestosterone, 17-S-estradiol, ethinyl estradiol, ethinyl estradiol 3-methyl ether, prednisolone, 17-á-hydroxyprogesterone acetate, 19-norprogesterone, norgestrel, norethindrone, norethisterone, norethiederone, progesterone, norgesterone, norethynodrel, aspirin, indomethacin, naproxen, fenoprofen, sulindac, indoprofen, nitroglycerin, isosorbide dinitrate, propranolol, timolol, atenolol, alprenolol, cimetidine, clonidine, imipramine, levodopa, chlorpromazine, methyldopa, dihydroxyphenylalanine, theophylline, calcium gluconate, ketoprofen, ibuprofen, cephalexin, erythromycin, haloperidol, zomepirac, ferrous lactate, vincamine, diazepam, phenoxybenzamine, diltiazem, milrinone, mandol, quanbenz, hydrochlorothiazide, ranitidine, flurbiprofen, fenufen, fluprofen, tolmetin, alclofenac, mefenamic, flufenamic, difuinal, nimodipine, nitrendipine, nisoldipine, nicardipine, felodipine, lidoflazine, tiapamil, gallopamil, amlodipine, mioflazine, lisinolpril, enalapril, enalaprilat captopril, ramipril, famotidine, nizatidine, sucralfate, etintidine, tetratolol, minoxidil, chlordiazepoxide, diazepam, amitriptyline, and imipramine. Further examples are proteins and peptides which include, but are not limited to, bone morphogenic proteins, insulin, colchicine, glucagon, thyroid stimulating hormone, parathyroid and pituitary hormones, calcitonin, renin, prolactin, corticotrophin, thyrotropic hormone, follicle stimulating hormone, chorionic gonadotropin, gonadotropin releasing hormone, bovine somatotropin, porcine somatotropin, oxytocin, vasopressin, GRF, somatostatin, lypressin, pancreozymin, luteinizing hormone, LHRH, LHRH agonists and antagonists, leuprolide, interferons such as interferon alpha-2a, interferon alpha-2b, and consensus interferon, interleukins, growth hormones such as human growth hormone and its derivatives such as methione-human growth hormone and des-phenylalanine human growth hormone, bovine growth hormone and porcine growth hormone, fertility inhibitors such as the prostaglandins, fertility promoters, growth factors such as insulin-like growth factor, coagulation factors, human pancreas hormone releasing factor, analogs and derivatives of these compounds, and pharmaceutically acceptable salts of these compounds, or their analogs or derivatives.
Other bioactive agents, which may be delivered by nanotubes, include chemotherapeutic agents, such as carboplatin, cisplatin, paclitaxel, BCNU, vincristine, camptothecin, etopside, cytokines, ribozymes, interferons, oligonucleotides and oligonucleotide sequences that inhibit translation or transcription of tumor genes, functional derivatives of the foregoing, and generally known chemotherapeutic agents such as those described in U.S. Pat. No. 5,651,986.
The nanotube delivery system of the present invention can be used as a gene therapy delivery mechanism. Gene therapy compositions can be delivered to a subject by, for example, intravenous injection, local administration (Nabel and Nabel, U.S. Pat. No. 5,328,470, 1994), or by stereotactic injection (Chen et al., Gene therapy for brain tumors: regression of experimental gliomas by adenovirus-mediated gene transfer in vivo. Proc Natl Acad Sci USA. 91:3054–7(1994)).
**Banny this sounds like what we are seeing in your photos of your sol jel spheres
EXAMPLE 3
Preparation of Capped Nanotubes (Prophetic Example)
Monodisperse silica microspheres are prepared as described by W. Stöber et al., J Colloid Interface Sci. 1968, 26, 62–69. Briefly, 0.2 M tetraethylorthosilicate (Fisher, Fairlawn, N.J.) is precipitated in a mixture of ethanol, aqueous 0.2 M ammonia (Fisher, Fairlawn, N.J.) and 3.2M water. Surface sulfhydryl groups are introduced by including 3-mercaptopropyltrimethoxysilane (Aldrich, Milwaukee, Wis.) as described by J. S. Lee, S. et al., React. Funct. Polymers 2001, 49, 159–172. The nanosphere diameters are varied by adjusting reactant concentrations. Preferably, nanospheres having diameters approximately 30% larger than those of the nanotubes are preferred.
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hmmm... probably...