Dendrimer compositions and methods of synthesis

• US 8,945,508 B2
• Filed: 10/07/2010
• Issued: 02/03/2015
• Est. Priority Date: 10/13/2009
• Status: Expired due to Fees

• Current Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Original Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Inventors: Baker, James R. Jr., Huang, Baohua
• Primary Examiner(s): Hartley, Michael G
• Assistant Examiner(s): PERREIRA, MELISSA JEAN
• Application Number:
  US13/502,004
• Publication Number:
  US 20120259098A1
• Time in Patent Office: 1,580 Days
• US Class Current: 424/1.11
• CPC Class Codes: A61K 47/595 Polyamides, e.g. nylon polyamino acids A61K47/62
• CPC Class Codes: A61K 49/0002 General or multifunctional contrast agents, e.g. chelated agents
• CPC Class Codes: A61K 49/0043 Fluorescein, used in vivo
• CPC Class Codes: A61K 49/0054 Macromolecular compounds, i.e. oligomers, polymers, dendrimers
• CPC Class Codes: A61K 49/124 dendrimers, dendrons, hyperbranched compounds
• CPC Class Codes: A61K 51/065 conjugates with carriers being macromolecules
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C08G 73/028 Polyamidoamines

Abstract

The present invention relates to novel dendrimer compounds and methods of synthesizing the same. In particular, the present invention is directed to novel polyamidoamine (PAMAM) dendrimers, novel dendrimer branching units, methods for synthesizing such novel PAMAM dendrimers and functionalized dendrimers, as well as systems and methods utilizing the dendrimers (e.g., in diagnostic and/or therapeutic settings (e.g., for the delivery of therapeutics, imaging, and/or targeting agents (e.g., in disease diagnosis and/or therapy, etc.))).

Claims

1. A composition comprising a compound having the following formula:

2. The composition of claim 1, said compound having the following formula:

3. The composition of claim 1,

wherein said therapeutic agent if present is selected from the group consisting of chemotherapeutic agents, anti-oncogenic agents, anti-angiogenic agents, tumor suppressor agents, anti-microbial agents, expression constructs comprising a nucleic acid encoding a therapeutic protein, pain relief agents, pain relief agent antagonists, agents designed to treat arthritis, agents designed to treat inflammatory bowel disease, agents designed to treat an autoimmune disease, and agents designed to treat inflammatory pelvic disease;

wherein said targeting agent if present is selected from the group consisting of an agent binding a receptor selected from the group consisting of CFTR, EGFR, estrogen receptor, FGR2, folate receptor, IL-2 receptor, and VEGFR;

an antibody that binds to a polypeptide selected from the group consisting of p53, Muc1, a mutated version of p53 that is present in breast cancer, HER-2, T and Tn haptens in glycoproteins of human breast carcinoma, and MSA breast carcinoma glycoprotein;

an antibody selected from the group consisting of human carcinoma antigen, TP1 and TP3 antigens from osteocarcinoma cells, Thomsen-Friedenreich (TF) antigen from adenocarcinoma cells, KC-4 antigen from human prostrate adenocarcinoma, human colorectal cancer antigen, CA125 antigen from cystadenocarcinoma, DF3 antigen from human breast carcinoma, and p97 antigen of human melanoma, carcinoma or orosomucoid-related antigen;

transferrin; and

a synthetic tetanus toxin fragment;

wherein imaging agent if present is selected from the group consisting of fluorescein isothiocyanate (FITC), 6-TAMARA, acridine orange, and cis-parinaric acid;

wherein said trigger agent if present is configured for a function selected from the group consisting of permitting a delayed release of a functional group from the dendrimer, permitting a constitutive release of the therapeutic agent from the dendrimer, permitting a release of a functional group from the dendrimer under conditions of acidosis, permitting a release of a functional group from a dendrimer under conditions of hypoxia, and permitting a release of the therapeutic agent from a dendrimer in the presence of a brain enzyme.

4. The composition of claim 1, wherein said therapeutic agent is methotrexate, and wherein said targeting agent is folic acid.

5. The composition of claim 1, further comprising nanomaterials selected from the group consisting of gold nanoparticles, iron oxide nanoparticles, polymers, silica, albumin, quantum dots, and carbon nanotubes.

6. The composition of claim 1, wherein said compound is selected from the group consisting of