Nanoparticles for targeted delivery of anti-inflammatory agents

This technology is a method to treat atherosclerosis with nanoparticles containing inflammation-resolving compounds.

Unmet Need: Targeted delivery of anti-inflammatory agents for treating cardiovascular disease

Current treatment for atherosclerosis, which can cause cardiovascular disease, often involves using lipid-lowering drugs, such as statins. While statins are able to reduce mortality, they are not sufficient to prevent progression and can cause systemic side effects. Advances in vascular biology have revealed a pivotal role of inflammation in the pathophysiology of atherosclerosis. Although a number of promising arterial-wall targets have been identified and validated using molecular-genetic approaches in animal models, many of these are not amenable to systemic or oral delivery due to the nature of the compounds, lack of efficient delivery to plaques, safety concerns, and pharmacokinetic issues. Therefore, there remains a substantial need for methods to reduce inflammation as a potential treatment option for cardiovascular disease.

The Technology: Biodegradable nanoparticles for efficiently delivering therapeutics to sites of inflammation

The technology is a method that allows the delivery of inflammation-resolving compounds to arteries by encapsulating them into biodegradable polymeric nanoparticles that specifically target them to atherosclerotic sites. These nanoparticles have four main components: 1) a targeting element that can selectively bind to cells, tissues, or organs of the body; 2) a diagnostic agent that allows visualization of nanoparticles at the site of delivery; 3) an outside “stealth” layer that allows the particles to evade recognition by immune system components and increase particle circulation half-life; and 4) a biodegradable polymeric material, forming an inner core which can carry therapeutics and release the payloads at a sustained rate after systemic, intraperitoneal, or mucosal administration. As a result, this technology offers a potent method of targeted drug delivery for resolving inflammation and promote tissue repair without adverse systemic effects observed with untargeted therapies.

This technology has been validated in mouse models.

Applications:

• Treatment of cardiovascular disorders (e.g. atherosclerosis and ischemia)
• Treatment of gastrointestinal disorders that involve inflammation (e.g. inflammatory bowel disease)
• Autoimmune and/or inflammatory diseases (e.g. Alzheimer’s disease, arthritis, psoriatic arthritis,
  asthma, Crohn’s disease, ulcerative colitis, Parkinson’s disease, etc.)
• Autoimmune diseases (e.g. rheumatoid arthritis and systemic lupus erythematosus)

Advantages:

• Targeted delivery of inflammation-resolution therapeutics
• Decreased side-effects
• Lower doses required for therapeutic effects
• Varied NP packaging composition allows for different targeting sites
• Release controlled NP can reduce the frequency of administration
• Increased half-life

Lead Inventor:

Ira Tabas, MD, Ph.D.

Patent Information:

Patent Issued

Related Publications:

• Kamaly N, Fredman G, Fojas JJ, Subramanian M, Choi WI, Zepeda K, Vilos C, Yu M, Gadde S, Wu J, Milton J, Carvalho Leitao R, Rosa Fernandes L, Hasan M, Gao H, Nguyen V, Harris J, Tabas I, Farokhzad OC. “Targeted Interleukin-10 Nanotherapeutics Developed with a Microfluidic Chip Enhance Resolution of Inflammation in Advanced Atherosclerosis.” ACS Nano. 2016 May 24; 4(6): 745-10(5):5280-5292.

• Fredman G, Kamaly N, Spolitu S, Milton J, Ghorpade D, Chiasson R, Kuriakose G, Perretti M, Farokzhad O, Tabas I. “Targeted nanoparticles containing the proresolving peptide Ac2-26 protect against advanced atherosclerosis in hypercholesterolemic mice.” Sci Transl Med. 2015 Feb 18;7(275): 275ra20.

• Kamaly N, Fredman G, Subramanian M, Gadde S, Pesic A, Cheung L, Fayad ZA, Langer R, Tabas I, Farokhzad OC. “Development and in vivo efficacy of targeted polymeric inflammation-resolving nanoparticles.” PNAS. 2013 Apr 13; 110(16): 6506-6511.

Tech Ventures Reference:

• IR CU13129

• Licensing Contact: Joan Martinez