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CobaCyte™ - Cobalamin™ Mediated Disease Targeting


In many diseases which involve cell proliferation, there is increased demand for certain vitamins or vitamin analogs compared with normal tissue. Access Pharmaceuticals has developed technology which takes advantage of this increase in demand. By coupling drugs to Cobalamin™ (an analog of vitamin B12 or VB12), more drug is taken up by diseased cells. This effect can be amplified by attaching Cobalamin™ and several molecules of the drug to a polymer, or encapsulating the drug in a nanoparticle coated with Cobalamin™. Access owns several patents and patent applications which provide the company with a proprietary position in amplified Cobalamin™-mediated targeted delivery of drugs to diseased cells.

Cobalamin Nanoparticle

There are several diseases for which this targeting approach holds promise; for example, cancer, rheumatoid arthritis, psoriasis, acute leukemia, lymphomas, Crohn's disease, ulcerative colitis, and multiple sclerosis. Access Pharmaceuticals is developing applications of this technology in the area of oncology, while seeking collaborations and partnerships for development of this technology for other diseases.

Cobalamin Vitamin Table

Our initial research has focused on targeting with Cobalamin™, folic acid, biotin, and analogs of these substances. Not all cancer cells have increased demand for all vitamin analogs, so we have screened a wide variety of cancers to determine which cell types take up one or more of these three vitamin analogs. The chart below summarizes results from this screening process. Colors are used to highlight cells which show a high affinity for certain vitamin analogs, and the results clearly demonstrate that increased uptake of biotin appears to occur whenever cells also have increased demand for either Cobalamin or folic acid. These results were obtained from cell uptake studies in which the fluorescent dye Rhodamine was first attached to a polymer.

To provide efficacy data, studies were conducted in rodent tumor models. In one study, inhibition of tumor growth was determined using methotrexate, a toxic drug used for the treatment of cancer, and in several polymer-methotrexate conjugates. Linking several molecules of methotrexate to a polymer utilizes the principles of polymer therapeutics to enhance tumor uptake, while attachment of a vitamin analog to the polymer should increase efficacy further, if the tumor has a high demand for that analog.

Cobalamin Methotrexate Plot

The bar chart demonstrates the potential of this approach. The height of each bar reflects the average size of the tumor in rodents. From left to right the bars depict the average tumor size of untreated tumors, tumors following treatment with methotrexate, treatment with the methotrexate-polymer, treatment with methotrexate-polymer to which Cobalamin™ is attached and finally treatment with methotrexate-polymer with folic acid attached. While methotrexate alone does inhibit tumor growth, the methotrexate-polymer does significantly better when compared with either the untreated group, or the methotrexate group.

In another tumor growth inhibition study, tumors were treated with Daunorubicin alone and Daunorubicin linked with polymer. The chart shows much more effective tumor growth inhibition when Daunorubicin is linked to the polymer and even improved inhibition with the addition of Cobalamin™.

Cobalamin Dnm VB12 Graph


  • Access has conducted studies which have provided proof-of-principle of vitamin-mediated targeting of cancer cells as well as sites of some other diseases.
  • Efficacy of vitamin-targeted polymer conjugates was demonstrated in rodent tumor and rheumatoid arthritis models.
  • Access has patents and patent applications which provide intellectual property protection for disease targeting of polymers and nanoparticles using Cobalamin™, folates, and biotin.


Most pharmaceutical research programs involve the search for new pharmaceutical agents as replacements for existing agents. The replacements are justified based upon improved potency, greater specificity, and/or an improved therapeutic index. This type of research involves high risk and high cost. On the other hand, drug delivery and targeting technologies offer the possibility of improving the therapeutic profile of existing drugs with relatively low risk and low cost. Access Pharmaceutical’s proprietary Cobalamin™-mediated disease targeting technology provides a drug delivery and targeting option for a wide variety of diseases in which increased demand for vitamins or vitamin analogs in diseased cells is known to occur. In addition to the oncology program described here, Access has conducted initial studies demonstrating proof-of-concept that Cobalamin™-mediated targeting could be very effective in treating rheumatoid arthritis and colitis. Access’ approach involves the coupling of the drug to a polymer or the encapsulation of the drug in a nanoparticle and targeting these constructs to the sites of disease through the attachment of Cobalamin™. Access has considerable expertise in drug-particle encapsulation, drug-polymer conjugation, and the chemistry of Cobalamin™ attachment, and has developed in vitro, in vivo, and ex-vivo models for the biological evaluation of Cobalamin™-targeted drug delivery systems.

Access Pharmaceuticals is currently seeking development partnerships with biotech and pharmaceutical companies requiring a targeted approach to increase drug efficacy and/or decrease side-effects of novel active pharmaceutical compounds and/or improve the efficacy/safety profile of an established active pharmaceutical agent to gain a competitive advantage over other formulations.

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