Nanocarriers and their processing for diagnostics and therapeutics

Patent metadata

Field	Value
Publication number	US-2020375991-A1
Application number	US-202016739864-A
Country	US
Kind code	A1
Filing date	Jan 10, 2020
Priority date	Mar 14, 2014
Publication date	Dec 3, 2020
Grant date	—

Abstract

The compositions and methods of the invention provide compositions and methods for preferential targeting of tissues to delivery therapeutic or diagnostic agents. For example, such compounds are useful in the treatment of joint disorders those affecting articulating joints, e.g., injury-induced osteoarthritis as well as autoimmune diseases affecting joint tissue such as rheumatoid arthritis.

First claim

1 . A system for selective drug delivery to a bodily tissue comprising a rosette nanopiece composition comprising a cargo compound,
wherein a positively-charged nanopiece composition with net positive charge at pH 7-7.5 localizes or penetrates a negatively-charged tissue; wherein wherein a negatively-charged or weakly positively-charged nanopiece composition with net negative charge or weak positive charge at pH 7-7.5 localizes or penetrates a positively-charged tissue.

2 . The system of claim 1 , wherein said drug comprises a diagnostic reagent or a therapeutic compound.

3 . The system of claim 1 , wherein said net positive charge comprises a Zeta potential >+8 mV.

4 . The system of claim 1 , wherein said negatively charged tissue comprises cartilage tissue or a chondrocyte cell.

5 . The system of claim 1 , wherein said net negative charge comprises a Zeta potential <+30 mV.

6 . The system of claim 1 , wherein said positively charged tissue comprises neuronal tissue or comprises a neuron.

7 . The system of claim 1 , wherein said composition comprises a compound of Formula (II):

wherein,
X is CH or N;
R 2 is hydrogen or a linker group;
Y is absent when R 2 is hydrogen or is an amino acid or polypeptide; and
R 1 is hydrogen or aliphatic.

8 . The system of claim 1 , wherein said composition comprises a compound selected from

9 . The system of claim 7 , wherein R 2 comprises an amino acid side chain or is selected from:

and Y is absent.

10 . The system of claim 1 , wherein said composition comprises a compound of Formula (I):

wherein, X is CH or N;
R 2 is hydrogen or a linker group;
Y is absent when R 2 is hydrogen or is an amino acid or polypeptide; and
R 1 is hydrogen or aliphatic.

11 . The system of claim 1 , wherein said composition comprises a compound selected from

12 . The system of claim 10 , wherein R 2 comprises an amino acid side chain or is selected from:

and Y is absent.

13 - 20 . (canceled)

21 . A method of treating a disease or disorder comprising administration of an effective amount of a rosette nanopiece, wherein said nanopiece comprises a compound of Formula I or Formula II.

22 . A method of diagnosing a disease or disorder comprising administration of rosette nanopiece, wherein said nanopiece comprises a compound of Formula I or Formula II.

23 . The method of claim 21 , wherein said disease or disorder comprises an autoimmune, degenerative, inflammatory, infectious, cancerous, viral, fungal, injured, trauma, genetic, mechanical, nutritional or mal-alignment derived disease or disorder.

24 . (canceled)

25 . The method of claim 21 , wherein said nanopiece further comprises one or more analgesic agents, anti-inflammatory agents, immunosuppresive agents, antifungal agents, antibiotic agents, lubricants, anti-cancer agents, NMDA receptor antagonists, or antiviral agents.

26 . (canceled)

27 . The method of claim 21 comprising selective drug delivery to a bodily tissue comprising a rosette nanopiece composition comprising a cargo compound, said composition being sized to localize or penetrate a target tissue,
wherein a size of ≤100 nm in at least one dimension localizes or penetrates synovium, ocular tissue, dermatologic tissue, mucosal tissue, or pulmonary tissue;
wherein a size of <90 nm in at least one dimension localizes or penetrates cartilage with inflammation or defect;
wherein a size of ≤50 nm in at least one dimension localizes or penetrates kidney tissue;
wherein a size of <30 nm in at least one dimension localizes or penetrates healthy, intact cartilage; or
wherein a size of ≤20 nm in at least one dimension localizes or penetrates heart tissue.

28 . (canceled)

29 . The method of claim 21 , wherein the disease or disorder diseases and/or disorders affects epithelial, connective, muscle and/or nervous tissues.

30 . The method of claim 21 , wherein the tissue or organ disease comprises amyloidosis, atiral fibrillation, convulsion, cramp, dermatomyositis, enchondroma, fibroma, lumbao, heritable connective tissue disorder, Marfan syndrome, Peyronie's disease, Ehlers-Danlos syndrome, Osteogenesis imperfecta, Stickler syndrome, Alport syndrome, Congenital contractural arachnodactyly, autoimmune connective tissue disorder, systemic lupus erythematosus (SLE), rheumatoid arthritis, Scleroderma, Sjoegren's syndrome, mixed connective tissue disease, psoriatic arthritis, scurvy, muscle disease, muscle tumour, muscular dystrophy, disuse atrophy, denervation atrophy, Duchenne muscular dystrophy, facioscapulohumoral muscular dystrophy, hepatic disease, myasthenia gravis, myopathy, myositis, myositis ossificans, cancer, fibromyalgia, muscle fatigue, spasm, spasticity, sprain, strain, brain injury, spinal cord injury, gliomas, neuroeptheliomatous, hypertension, cardiovascular disease, diabetes, Alzheimer's disease, cystitis, AIDS, rickets, or nerve sheath tumors.

31 . The method of claim 22 , wherein said disease or disorder comprises an autoimmune, degenerative, inflammatory, infectious, cancerous, viral, fungal, injured, trauma, genetic, mechanical, nutritional or mal-alignment derived disease or disorder.

Assignees

• Rhode Island Hospital

Inventors

• Chen Qian
• Chen Yupeng
• Yu Hongchuan
• Ehrlich Michael G

Classifications

• Y02A50/30

  Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change · CPC title

• A61K49/0095

  Nanotubes · CPC title

• G01N2800/102

  Arthritis; Rheumatoid arthritis, i.e. inflammation of peripheral joints · CPC title

• A61K9/5123

  Organic compounds, e.g. fats, sugars · CPC title

• C12Q1/6883

  for diseases caused by alterations of genetic material · CPC title