EP1100475A1 - Use of drug-loaded nanoparticles for the treatment of cancers - Google Patents
Use of drug-loaded nanoparticles for the treatment of cancersInfo
- Publication number
- EP1100475A1 EP1100475A1 EP99926509A EP99926509A EP1100475A1 EP 1100475 A1 EP1100475 A1 EP 1100475A1 EP 99926509 A EP99926509 A EP 99926509A EP 99926509 A EP99926509 A EP 99926509A EP 1100475 A1 EP1100475 A1 EP 1100475A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- nanoparticles
- treatment
- mammal
- cancer
- substance
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/136—Amines having aromatic rings, e.g. ketamine, nortriptyline having the amino group directly attached to the aromatic ring, e.g. benzeneamine
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0085—Brain, e.g. brain implants; Spinal cord
-
- 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
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5138—Organic macromolecular compounds; Dendrimers obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- 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
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5146—Organic macromolecular compounds; Dendrimers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
- A61K9/5153—Polyesters, e.g. poly(lactide-co-glycolide)
-
- 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
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5161—Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin
-
- 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
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5169—Proteins, e.g. albumin, gelatin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Definitions
- the present invention relates to the use of drug-loaded nanoparticles for preparing a medicament for the treatment of cancer, particularly for the treatment of cancer in the brain, even more particularly for the treatment of brain cancer in humans.
- the invention also relates to a process for the treatment of brain cancer, particularly for the treatment of brain cancer in humans, by ad ⁇ iinistering an effective amount of nanoparticles containing a substance which has effect in the cancer treatment or has immunosuppressive effects.
- blood brain barrier refers to the bbb in the narrower sense, i. e. in the sense this term is used usually by a person skilled in the medical field, as well as to the blood spinal barrier and blood retina barrier.
- nanoparticles prepared in accordance with teachings of the prior art, particularly of the above two Patent Applications may be loaded with a substance having effect in the treatment of cancers, particularly having effect in the treatment of cancers in the brain, for example in humans, in an effective amount and may then be coated with a suitable surfactant so as to allow that drug-loaded nanoparticles to pass across the bbb and to deliver the effective drug to the site where it may exhibit its anticancer and/or immunosuppressive activity. It was particularly found that, by a suitable selection of the combination drug/surfactant, an effective use of such nanoparticles loaded with the drug and coated with a surfactant in the treatment of cancers, particularly of cancers in the brain, may be pro viced.
- the invention relates to the use of nanoparticles made of a polymeric material, said nanoparticles comprising said polymeric material, one or more substance(s) physiologically effective in the treatment of cancer upon delivery to a mammal, one or more stabilizer(s) for said nanoparticles allowing targeting of said physiologically effective substance(s) to a specific site within or on said mammalian body and/or a surfactant coating on said nanoparticles, said nanoparticles optionally being provided within a physiologically acceptable carrier and/or diluent allowing the delivery of said nanoparticles to the target within said mammal after administration, for the manufacture of a medicament for the treatment of cancer in said mammal.
- the treatment of cancer is a treatment of cancer in the brain.
- the brain cancer treatment is a treatment to a human.
- the terms "cancer” and “tumor(s)” are used in the description and claims in a synonymous manner.
- the nanoparticles used in the present invention for the cancer treatment are nanoparticles which mainly consist of three major components, i. e. the polymeric material which is used to form a wall either incorporating the drug or physiologically effective substance(s) or containing said substance(s) adsorbed or absorbed thereto, e. g. onto its surface; the physiologically effective substance or substances contained within or on said nanoparticle; and a stabilizer or more than one stabilizer allowing the passage of said nanoparticle across the bbb.
- the present invention comprises as one of the preferred embodiments the use of said nanoparticles, wherein said nanoparticles comprise particles of said polymeric material having a diameter of below 1,000 nm, preferably of from 1 to 1,000 nm.
- the invention relates to the use of said nanoparticles, wherein said polymeric material the nanoparticles are consisting of is selected from the group consisting of polyacrylates, polymethacrylates, poly-cyanoacrylates, polyacrylamides, polylactates, polyglycolates, polyanhydrates, polyorthoesters, gelatin, polysaccharides, -dbumin, polystyrenes, poly vinyls, polyacro ⁇ ein, polyglutaraldehydes and derivatives, copolymers and rnixtures thereof.
- polyacrylates polymethacrylates, poly-cyanoacrylates, polyacrylamides, polylactates, polyglycolates, polyanhydrates, polyorthoesters, gelatin, polysaccharides, -dbumin, polystyrenes, poly vinyls, polyacro ⁇ ein, polyglutaraldehydes and derivatives, copolymers and rnixtures thereof.
- the nanoparticles according to the invention there is/are provided within or on said nanoparticles (incorporated, absorbed and/or adsorbed) one or more substances which are physiologically effective in the treatment of cancer upon delivery to a mammal.
- the substances may be a single substance or may be two or even more substances which may act on the human body on a separate route or on a combined route or even synergistic route.
- said physiologically effective substance(s) to be delivered to said mammal comprise(s) one or more chemotherapeutic agent(s) for the cancer treatment, particularly for the treatment of cancer in the brain of said mammal, more particularly for the treatment of cancer in the human body, i. e. the brain.
- chemotherapeutic agent(s) for the cancer treatment particularly for the treatment of cancer in the brain of said mammal, more particularly for the treatment of cancer in the human body, i. e. the brain.
- chemotherapeutic anticancer agent is selected from the group consisting of alkylating agents, antimetabolites, natural anticancer products, hormones, metal coordination complexes and mixtures thereof.
- chemotherapeutic anticancer agent is selected from the group consisting of alkylating agents, antimetabolites, natural anticancer products, hormones, metal coordination complexes and mixtures thereof.
- nitroso ureas e. g. Carmustine (BCNU), Lomustine (CCNU), Semustine (methyl- CCNU) and Nimustine (ACNU);
- BCNU Carmustine
- CCNU Lomustine
- CCNU Semustine
- ACNU Nimustine
- folic acid analogs e. g. Methotrexate
- - purine analogs e. g. Mercaptopurine and Azathioprine
- - vinca alkaloids e. g. Vinblastine, Nincristine and Vindesine
- epipodophyllotoxins e. g. Etoposide and Teniposide
- antibiotics e. g. Dactinomycin, Daunorubicin, Doxorubicin, Epirubicin, Bleomycin A2, Mitomycin C and Mitoxantrone;
- - estrogens e. g. Diethyl stilbestrol
- - gonadotropin-releasing hormon analogs e. g. Leuprolide, Buserelin and Goserelin
- antiestrogens e. g. Tamoxifen and Ammoglutethimide
- a critical component of the nanoparticles used in the present invention is/are the stabilizer(s).
- only one stabilizer is used whereby a passage of the bbb by said nanoparticles loaded with the anticancer drugs can be afforded in a successful way, and the anticancer drugs in said nanoparticles are directed to the tumor site in the brain in a high concentration.
- the other critical component of the nanoparticles used in the present invention are the surfactant materials of the coating which materials are belonging to the same group of compounds as the above.
- the stabilizer may be present in the nanoparticles used in accordance with the present invention as a result of the manufacturing steps either in small remaining amounts or may form the coating allowing the passage of the effective substance(s) across the bbb.
- the separate coating may be provided.
- the outside wall of the nanoparticles used in the present invention is coated with the material allowing the passage of the bbb in a surprising manner.
- the application of the coating or the provision of the stabilizer in such nanoparticles is basically described in the above-mentioned International Patent Applications the disclosures of which are incorporated herein by reference.
- the material(s) of the stabilizer/ surfactant is/are selected selected from the group consisting of stabilizers/surfactants which allow a passage of said nanoparticles including said physiologically effective substance(s) across the blood brain barrier in said mammal and stabilizers/surfactants which allow a release of said physiologically effective substance(s) from said nanoparticles and a passage of said substance(s) across the blood brain barrier separate from said nanoparticles.
- said stabilizer/surfactant comprises a substance selected from the group consisting of polysorbates, dextrans, carboxylic acid esters of multifunctional alcohols, polyoxamers, polyoxamines, alkoxylated ethers, alkoxylated esters, alkoxylated mono-, di- and triglycerides, alkoxylated phenols and diphenols, substances of the Genapol R and Bauki R series, metal salts of carboxylic acids, metal salts of alcohol sulfates, and metal salts of sulfosuccinates and mixtures of two or more of said substances.
- said stabilizer/surfactant comprises a substance selected from the group consisting of polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, polysorbate 81, polysorbate 85, dextran 12.000, dextran 70,000, fatty acid esters of glycerol and sorbitol as glycerol monostearate, sorbitan monostearate and sorbitan monooleate, polyoxamer 188 (Pluronic R F68), ethoxylated ethers, ethoxylated esters, ethoxylated triglycerides, ethoxylated phenols and diphenols, metal salts of fatty acids and of fatty alcohol sulfates, more preferably the sodium salts of fatty acids and of fatty alcohol sulfates
- the most preferred stabilizers/surfactant materials are selected from the group consisting of polysorbate 80, polysorbate 85, dextran 12,000 or dextran 70,000 and mixtures thereof and mixtures of said stabilizers with other stabilizers. With the latter compounds, a superior use of the nanoparticles in the anticancer treatment can be achieved, particularly in the treatment of brain cancers in humans.
- said carrier and/or diluent which is used for the aclministration of the nanoparticles used in the present invention is/are selected from the group consisting of water, physiologically acceptable aqueous solutions containing salts and/or buffers and any other solution acceptable for administration to a mammal.
- nanoparticles comprising said polymeric material, one or more substance(s) physiologically effective in the treatment of cancer upon delivery to a mammal, one or more stabilizer(s) for said nanoparticles allowing targeting of said physiologically effective substance(s) to a specific site within said mammalian body and/or a surfactant coating on said nanoparticles, said nanoparticles optionally being provided within a physiologically acceptable carrier and/or diluent allowing the delivery of said nanoparticles to the target within said mammal after administration, for the treatment of cancer in said mammal.
- a process for the treatment of cancer particularly of brain cancer, in mammals, said process comprising the step of administering to said mammals nanoparticles made of a polymeric material, said nanoparticles comprising said polymeric material, one or more substance(s) physiologically effective in the treatment of cancer upon delivery to a mammal, one or more stabilizer(s) for said nanoparticles allowing targeting of said physiologically effective substance(s) to a specific site within said mammalian body and/or a surfactant coating on said nanoparticles, said nanoparticles optionally being provided within a physiologically acceptable carrier and/or diluent allowing the delivery of said nanoparticles to the target within said mammal after administration, in an amount effective for the treatment of cancer.
- the administration is an i.v. administration. It is particularly preferred that the treatment is a treatment of brain cancer, e. g. in mammals as for example humans.
- the invention is further exemplified by the subsequent example which, however, should not be understood to limit the invention.
- the anti-tumor effect of doxorubicin preparations was tested in rats with an intracranially transplanted glioblastoma 101/8. This tumor is known to have a substantial number of receptors to the epidermal growth factor.
- mice were treated with 1.5 mg/kg x 3 of doxorubicin which makes a total course dose of 4.5 mg/kg (the total dose for mice is usually 7 to 8 mg/kg).
- the drugs were administered i/v on the day 2 (48 h after implantation of the tumor), day 5 and day 8 after tumor implantation.
- Drug preparations were administered as usual in saline or in 1 % Tween R 80 .
- the suspension was added with 1 % Tween R 80 with stirring. The mixture was incubated for 2 h.
Abstract
Description
Claims
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/EP1999/003838 WO2000074658A1 (en) | 1999-06-02 | 1999-06-02 | Use of drug-loaded nanoparticles for the treatment of cancers |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1100475A1 true EP1100475A1 (en) | 2001-05-23 |
Family
ID=8167319
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP99926509A Ceased EP1100475A1 (en) | 1999-06-02 | 1999-06-02 | Use of drug-loaded nanoparticles for the treatment of cancers |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP1100475A1 (en) |
JP (1) | JP2003501379A (en) |
AU (1) | AU4373499A (en) |
WO (1) | WO2000074658A1 (en) |
Families Citing this family (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU3176097A (en) | 1997-06-13 | 1998-12-30 | Medinova Medical Consulting Gmbh | Drug targeting system, method of its preparation and its use |
US7153525B1 (en) | 2000-03-22 | 2006-12-26 | The University Of Kentucky Research Foundation | Microemulsions as precursors to solid nanoparticles |
AUPR011700A0 (en) | 2000-09-14 | 2000-10-05 | Austin Research Institute, The | Composition comprising immunogenic virus sized particles (VSP) |
DE10121982B4 (en) * | 2001-05-05 | 2008-01-24 | Lts Lohmann Therapie-Systeme Ag | Nanoparticles of protein with coupled apolipoprotein E to overcome the blood-brain barrier and process for their preparation |
US6878693B2 (en) | 2001-09-28 | 2005-04-12 | Solubest Ltd. | Hydrophilic complexes of lipophilic materials and an apparatus and method for their production |
EP1448174A2 (en) * | 2001-09-28 | 2004-08-25 | Solubest Ltd | Water soluble nanoparticles of hydrophilic and hydrophobic active materials |
US7763663B2 (en) | 2001-12-19 | 2010-07-27 | University Of Massachusetts | Polysaccharide-containing block copolymer particles and uses thereof |
DE60229003D1 (en) * | 2002-07-29 | 2008-10-30 | Nanodel Technologies Gmbh | NANOPARTICLES FOR DNA DELIVERY TO A TARGET ORGAN |
US20060228420A1 (en) * | 2005-03-15 | 2006-10-12 | Queen Mary & Westfield College | Pharmaceutical compositions comprising microparticles for delivery into neurons |
KR20080080488A (en) | 2005-09-30 | 2008-09-04 | 티티아이 엘뷰 가부시키가이샤 | Electrode structure for iontophoresis used to administer drug enclosed in nanoparticle and iontophoresis device making use of the same |
US9486408B2 (en) | 2005-12-01 | 2016-11-08 | University Of Massachusetts Lowell | Botulinum nanoemulsions |
DE102005062440B4 (en) * | 2005-12-27 | 2011-02-24 | Lts Lohmann Therapie-Systeme Ag | Protein-based carrier system for the resistance of tumor cells |
WO2007079193A2 (en) | 2005-12-30 | 2007-07-12 | Tti Ellebeau, Inc. | Iontophoretic systems, devices, and methods of delivery of active agents to biological interface |
EP2072079A1 (en) | 2006-10-10 | 2009-06-24 | TTI ellebeau, Inc. | Artificial tooth-type iontophoresis device |
JP5201763B2 (en) * | 2007-02-28 | 2013-06-05 | 昇一 城武 | Method for producing mixed fine particle capsules comprising particles having different average particle sizes |
EP1985286A1 (en) * | 2007-04-24 | 2008-10-29 | Biocompatibles UK Limited | Microspheres for treatment of brain tumours |
WO2010040173A1 (en) * | 2008-10-08 | 2010-04-15 | Commonwealth Scientific And Industrial Research Organisation | A method of delivering functional agents across the blood-brain barrier |
GB201209517D0 (en) * | 2012-05-29 | 2012-07-11 | Univ Birmingham | Nanoparticles |
CN103623424B (en) * | 2012-08-24 | 2016-08-03 | 复旦大学 | A kind of brain targeting gene based on polymethacrylates passs release system |
CN110198703A (en) | 2016-11-21 | 2019-09-03 | 艾里奥治疗公司 | The transdermal delivery of big reagent |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2634397B2 (en) * | 1986-12-31 | 1991-04-19 | Centre Nat Rech Scient | PROCESS FOR THE PREPARATION OF DISPERSIBLE COLLOIDAL SYSTEMS OF A PROTEIN IN THE FORM OF NANOPARTICLES |
HUT75469A (en) * | 1994-02-28 | 1997-05-28 | Medinova Med Consulting Gmbh | Drug targeting system, method for preparing same and its use |
AU3176097A (en) * | 1997-06-13 | 1998-12-30 | Medinova Medical Consulting Gmbh | Drug targeting system, method of its preparation and its use |
DE19745950A1 (en) * | 1997-10-17 | 1999-04-22 | Dds Drug Delivery Service Ges | Drug carrier particle for site specific drug delivery, especially to CNS |
-
1999
- 1999-06-02 EP EP99926509A patent/EP1100475A1/en not_active Ceased
- 1999-06-02 WO PCT/EP1999/003838 patent/WO2000074658A1/en not_active Application Discontinuation
- 1999-06-02 JP JP2001501195A patent/JP2003501379A/en active Pending
- 1999-06-02 AU AU43734/99A patent/AU4373499A/en not_active Abandoned
Non-Patent Citations (1)
Title |
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See references of WO0074658A1 * |
Also Published As
Publication number | Publication date |
---|---|
WO2000074658A1 (en) | 2000-12-14 |
AU4373499A (en) | 2000-12-28 |
JP2003501379A (en) | 2003-01-14 |
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