New Non-Toxic Fullerene-Based Bisphosphonated Drug for Osteoporosis Treatment Promotes Bone Growth-Technology License Available from Rice University

Rice University Office of Technology Transfer is offering a  license for non-toxic polyfluorobisphosphonated fullerenes used for the treatment of osteoporosis.  The formulation is patent pending.

Bone replacement materials are of increasing importance in the orthopedic, cranio-maxillofacial, and dental fields. Materials that set into solid, calcium-containing mineral products are of particular interest as such products can closely resemble the mineral phase of natural bone and are potentially remodelable. The bone replacement materials are used for repairing fractured bone, strengthening cancerous bone, reinforcing osteoporotic bone, accelerated dental implant anchorage, and the like.

There is a need for a bone replacement material having improved biocompatibility with natural bone. Further needs include a bone replacement material that facilitates the regeneration and growth of bone. Additional needs include a bone replacement material that is biodegradable.

In the treatment of osteoporosis and other bone disorders, it is desirable to deliver therapeutic compounds to the bone. However, it is known that certain substances, although therapeutic, are too toxic to be transported in the human body in free form. For example, fluoride anion (F–) is known to be an active therapeutic agent for osteoporosis, and the only known agent that can generate new bone matrix and new mineral from previously inactive areas. It both improves bone strength and helps prevent fractures. Yet it is too toxic to be administered in free form, such as by injecting NaF in aqueous solution intravenously.

One recently approved treatment for bone disease is a class of chemicals known as biphosphonates. Bisphosphonates bind to bone, slowing osetoporosis and allowing new bone to be formed. However, because this effect is temporary, bone mass is not substantially increased in the long term. Because new bone is not formed, bones are left weakened and prone to later injury.

Hence, bisphosphonates alone are not entirely satisfactory. There remains a need for a suitable compound that inhibits bone resorption and promotes new bone formation so as to produce a net bone gain without adversely affecting the patient. Further, such a compound would be targeted to bone, permitting the release of a therapeutic agent at the site of the bone, and hindering any, potentially harmful release of the agent to the rest of the body. 

Professor Lon Wilson in the Dept. of Chemistry has pioneered a new class of drugs for the treatment of osteoporosis and possibly other bone disorders. This medical advancement provides a non-toxic, biologically active composition that is capable of promoting bone growth while simultaneously inhibiting bone resorption, so as to produce a net bone gain. In its most essential design, the drug is comprised of a bisphosphonate group linked to a fullerene molecule. Alternatively, the bisphosphonate group can form chemical bonds directly with the fullerene, or between a linking molecule.

 A preferred method of synthesis of a fullerene-based bisphosphonated drug includes attachment of a water-solubilizing group, and attachment of a therapeutic agent. A plurality of fluorine atoms, as a therapeutic agent, are bound to one hemisphere the fullerene, thus hindering toxicity. Further it is believed that fluorine anion is released over time at the surface of the bone, due partly to the basic and nucleophilic environment of bone’s surface.

It is known that fluorine anion generates new bone matrix and new mineral from previously inactive areas. It is envisioned that polyfluorobisphosphonated fullerenes, as bimodal drugs, can deliver the two bisphosphonate and F– components to bone in a single, non-toxic “package” that is easily absorbed in the gastrointestinal tract.

Professor Wilson's research program involves bringing carbon nanotechnology to the fields of biology and medicine. The nanoparticle "building blocks" of this program are fullerenes (C₆₀), endohedral metallofullerenes (M@C₆₀), and ultra-short (20 nm long) single-walled carbon nanotube capsules (US-tubes). Externally, these carbon nanostructures are being chemically derivatized to make them biocompatible and cell-specific through peptide and antibody targeting. Internally, the nanostructures are being loaded with materials of medical interest for diagnostic and therapeutic medicine.

Other materials of interest include Fe₂O₃ and Gd³⁺ ions for magnetic resonance imaging (MRI), I2 molecules for X-ray computed tomography (CT) imaging and alpha-particle radionuclides (Ac³⁺-225 and At-211) for alpha-radioimmunotherapy of single-cell cancers. Cancer therapies are also being developed that take advantage of superparamagnetic nanostructures, such as Gd³⁺@US-tubes, that are simultaneously diagnostic (MRI-guided) and therapeutic (magnetic hyperthermia) agents in a single package. All these carbon nanostructures, with their medical cargos, are designed to be among the first intracellular agents, since the future of medicine will involve the early detection of disease at the cellular level when it is most treatable.

Nanoengineered materials promise great advances in medicine, and, working with colleagues at various medical centers, our goal is to bring key, high-performance materials to the clinic as soon as possible.

Rice reports a patent application has been filed to cover the use of  fullerenes for the treatment of osteoporosis.

Contact: Brian Phillips, Rice University Office of Technology Transfer
Tel: 713-348-6278
Brian.j.phillips@rice.edu

Invention Abstract: Fullerenes for the Treatment of Osteoporosis
Technology ID: #20025
Investigator: Professor Lon Wilson

http://ott.rice.edu/index.cfm