Nanoscale Drug Delivery Systems by Gregor Wolbring December 15, 2007

I covered nano-pharmaceuticals in my October 15 column. In this one, I have highlighted advances in different nanoscale material-based carrier systems for drugs (nanoscale or otherwise). I’ll cover nanodelivery-related patent issues in February 2008. Nanoscale material based drug delivery systems are a lucrative market and advances are happening quickly.

Flynn and Wei estimated that annual prescription expenditures in the United States were $117 billion in 2000 and that this would grow to $366 billion by 2010, “making nanomedicine applications for drug delivery an attractive market for manufacturers and investors.” (1)

A recent report titled “Innovation in Drug Delivery: The Future of Nanotechnology and Non-Invasive Protein Delivery” says: "Drug delivery is one of the most dynamic and fast-growing sectors of the pharmaceutical industry. The high level of innovation in this sector is evolving at a fast pace.”

Cientifica -- one of the oldest nanotechnology consulting firms -- projected in its report “The Nanoparticle Drug Delivery Market” that the total market for nanotechnology-enabled drug delivery will rise to $26 billion by 2012 from its current size of $3.39 billion -- a compound annual growth rate of 37%. But the report says this is just the beginning: “the market could steeply rise after 2012, reaching potentially $220 billion by 2015 for these nano-enabled compounds.” More than 60 different companies are covered, including 38 engaged in drug formulation and 23 in drug delivery.

A number of recent conferences have been held on this subject. The Ninth Annual Chinese-American Kavli Frontiers of Science Symposium covered polymeric nanopharmaceuticals among other topics. The fifth nanomedicine and drug delivery symposium took place in November in Boston. The symposium program is located here.

Researchers have made many recent advances in nanodelivery technology:

• Mitragotri and others have attached polymeric nanoparticles to red blood cells, which might become a new way to deliver drugs. The research appears in the July issue of the Journal of Experimental Biology and Medicine.
• Anan Yaghmur, Michael Rappolt, Peter Laggner and Shuguang Zhang have reported the formation of dynamic nanostructures of lipid-like peptides which provide new strategies to create systems with excellent potential for a variety of biotechnological applications such as the encapsulation of water-insoluble drugs and delivery of biologically active materials.
• U.S.scientists have developed an unusual nano-centered drug delivery system in which the drug itself acts as the delivery vehicle. The process is described in detail in the journal Molecular Pharmaceutics.
• Researchers in France have developed a simple way to make inorganic microspheres that could be used to carry and release drugs.
• Researchers led by Sangeeta Bhatia at Harvard-MIT Division of Health Sciences and Technology and in MIT’s Department of Electrical Engineering and Computer Science have published a paper called “Nanoparticle Self-Assembly Directed by Antagonistic Kinase and Phosphatase Activities,” which is about remotely controlling nanoparticles used to fight cancer (see here and here).

There are many useful information sources online:

• A variety of videocasts related to nanodrug delivery can be found here, here and here.
• Biomedical applications and current status of peptide and protein nanoparticulate delivery systems can be found here
• Methods for preparation of drug-loaded polymeric nanoparticles can be found here.
• A review of dendrimers -- one class of nanoscale drug carriers -- can be found in a 2006 issue of the journal Nanomedicine. Other coverage of dendrimers can be found here and here.
• An overview of the development of novel nanoscale delivery and targeting systems of genetic material -- especially those encoding osteogenic (bone) growth factors -- can be found here.
• Typing in nanocrystals -- another group of nanoscale drug carriers -- here generates over 245 review articles.
• Papers on nanocrystals can be found here. Other write-ups can be found here.
• A presentation by Ruth Duncan of the Centre for Polymer Therapeutics, Welsh School of Pharmacy, Cardiff University, references numerous nanodrugs and delivery systems.
• The website of the summer school on women-in-nano links to a paper by P. Calvo with the title “Liposomes, dentrimers and other drug delivery systems: nanomedicine and industrial view.”

These are just a few snapshots of recent research in nano drug-delivery systems. Conducting research in this area makes sense. Studies have shown that existing drug delivery systems are less than perfect. In 2000, 15% of all hospital admissions (see here) were due to adverse drug effects, with 100,000 deaths (see here). Adverse drug effects have resulted in $136 billion in healthcare costs (see here and (2)).

Drug delivery is a rapidly expanding subsection of the market for therapeutic drugs. The report “Advanced Drug Delivery: Technologies, Applications, and Markets” estimated that the global drug delivery market would be worth $20 billion in 2003. However, in 2002, the market already represented about 13.5% of global pharmaceutical sales ($53.8 billion) and by 2007, it is expected to account for 39%. Growth in this market, the Nanoforum Consortium reports, will continue at an average annual rate of 11%.

A 2006 report “Effective Licensing & Commercialisation of Drug Delivery Systems” by Pharmaventures identifies the following market drivers as important for the development of drug delivery systems: improving the therapeutic index, patient compliance, patent prolongation, and life cycle management. Product differentiation and the promise of a drug discovery revolution are other drivers.

The Choice is Yours

In a 2001 report, the Premier's Advisory Council on Health in the Canadian province of Alberta recognized the existence, potential, and problems of emerging drug delivery systems. The context paper "What factors drive costs in health care" (see here or contact me and I’ll send you a copy) stated: “Nanorobotics, liposome technology and other exotic delivery systems will improve treatments but raise costs significantly.”

So what to do? We need to ask a few questions. How do we govern the development and uptake of nanodelivery systems? Are there any safety issues with these systems? What about the cost? Can a health care system afford them?

Gregor Wolbring is a biochemist, bioethicist, disability/vari-ability/ability studies scholar, and health policy and science and technology governance researcher at the University of Calgary. He is a member of the Center for Nanotechnology and Society at Arizona State University; Part Time Professor at Faculty of Law, University of Ottawa, Canada; Member CAC/ISO - Canadian Advisory Committees for the International Organization for Standardization section TC229 Nanotechnologies; Member of the editorial team for the Nanotechnology for Development portal of the Development Gateway Foundation; Chair of the Bioethics Taskforce of Disabled People's International; and former Member of the Executive of the Canadian Commission for UNESCO (2003-2007 maximum terms served). He publishes the Bioethics, Culture and Disability website, moderates a weblog for the International Network for Social Research on Disability, and authors a weblog on NBICS and its social implications.

Resources

Flynn, Ted; and C. Wei. The pathway to commercilization for nanomedicine (2005). Nanomedicine: Nanotechnology, Biology and Medicine 1, 1 47-51. Johnson, J.A.; and J. L. Booman. Drug-related morbidity and mortality. A cost-of-illness model. Arch Intern Med. 1995; 155:1949-56.

Please contact the author for information on this reference or for additional future references at gwolbrin@ucalgary.ca