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news.Aphios has been granted United States Patent No. 8,637,074 B2 entitled “Methods for Co-Encapsulation of Combination Drugs and Co-Encapsulated Drug Product,” for its green nanoencapsulation technology.
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This invention is for a nanotechnology process to co-encapsulate hydrophobic drugs and hydrophilic drugs in phospholipid nanosomes for use in combination therapy by means of Aphios’ SuperFluids technology platform.
With this technology, nontoxic supercritical or near-critical fluids with or without polar cosolvents are utilized to solubilize phospholipid materials and hydrophobic drugs, and form small, uniform liposomes that co-encapsulate hydrophobic drugs in their lipid bilayers and hydrophilic drugs in their aqueous cores.
This patent also claims a therapeutic drug product that combines a hydrophobic drug consisting of topoisomerase 1 (Top1) inhibitors such as camptothecin, irinotecan, topotecan and derivatives thereof and a hydrophilic drug selected from the group consisting of tyrosyl-DNA phosphodiesterase (Tdp1) inhibitors such as an aminoglycoside antibiotics like tetracycline and ribosome inhibitors like puromycin for drug-resistant cancers.
Such a combination drug APH-0804 is based on research by NCI scientists that demonstrate that the enzyme Tdp1 can repair Top1-DNA covalent complexes by hydrolyzing the tyrosyl-DNA bond. Inhibiting Tdp1 has the potential to enhance the anticancer activity of Top1 inhibitors and also to act as anti-infective agents.
Dr. Trevor P. Castor, the Company’s President and CEO explains "We anticipate that the nanosomal formulations will result in reduced systemic toxicity, due to masking of cytotoxic effects of camptothecins and Tdp1 inhibitors. Additionally, the stability of the lactone ring in nanosomes will be improved as a result of protection from the neutral pH of the blood stream. By increasing residence time in the circulatory system, nanosomes will increase therapeutic efficacy of the combination drugs.
"Pegylated phospholipids can be utilized to provide steric hindrance that will increase residence time and therapeutic efficacy as is done with Doxil, liposome encapsulated doxorubicin.
"Furthermore, phospholipids linked with cancer-specific ligands can be utilized to target co-encapsulated camptothecin and Tdp1 inhibitors to cancers of the colon, lung or ovary. Such smart targeting will further reduce toxicities associated with Top1 and Tdp1 inhibitors while increasing efficacy and therapeutic index."