Treatment that employs large size material for drug delivery presents problems such as poor bioviability, low solubility, a lack of targeted delivery and generalized side effects. The application of nanotechnology for drug delivery provides the potential for enhanced treatments with targeted delivery and fewer side effects. Nanotechnology drug delivery applications occur through the use of designed nanomaterials as well as forming delivery systems from nanoscale molecules such as liposomes.
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Applying nanotechnology to drug delivery should achieve the following benefits:
- Improve the ability to deliver drugs that are poorly water soluble.
- Provide site-specific targeting to reduce drug accumulation within healthy tissue.
- Help retain the drug in the body long enough for effective treatment.
- The extension of drug bioactivity through protection from the biological environment.
- Allow for the transportation of drugs across epithelial and endothelial barriers.
- Combine therapeutic and diagnostic modalities into one agent.
The enhanced permeability and retention effect (EPR)
An important discovery for drug delivery nanotechnology applications is the enhanced permeability and retention effect. Molecules at the nanoscale tend to accumulate in tumor tissue more than in normal tissue. This is because fast growing tumors have a great oxygen demand and require the fast generation of blood vessels. The blood vessels produced are structurally abnormal and contain pores which allow nanoscale molecules to permeate through to the tumor tissue. As fast growing tumors also lack functioning lymphatic systems, the enhanced permeability and retention effect should allow for targeted delivery of chemotherapeutic drugs.
Studies have analyzed which types of tumors have responded best to selective drug release via the enhanced permeability and retention effect. Data from clinical trials found that lung, breast and ovarian cancers have the best response with greater expression of the polymer drug conjugate tested. The results indicated a high enhanced permeability and retention effect in these tumor types. It has been suggested that patient selection in the form of pre-screening the individual enhanced permeability and retention effect will develop the clinical potential of this drug delivery system further.
Nanotechnology drug delivery for infection treatment
The use of nanotechnology for drug delivery is also being applied to infection treatment in light of increasing strains of drug-resistant bacteria. Though the enhanced permeability and retention effect is predominantly associated with cancer treatments, there are shared similarities in terms of pathophysiological pathways that mean the effect could be utilized for infection treatment. During infection, vasodilation rapidly occurs meaning the permeability of capillaries increases. Though the retention effect in cancer tumors is due to the lack of a functioning lymphatic system, studies have found rapid lymphatic clearance of small molecules during infection does not occur as expected. In fact, dysfunctional lymphatic drainage is a characteristic of infection. Nanoantibiotics will utilize this effect to enhance infection treatment via the application of both nanoparticles with antimicrobial therapies and nanosized biological molecules for improved antibiotic drug delivery.
Nanotechnology drug delivery for treatment of heart disease
Nanotechnology is also being used to advance the delivery of drug treatments for heart disease. Targeted drug delivery to diseased heart tissue can occur because inflammatory changes also produce increased vascular permeability and retention of nanoscale molecules. Coronary artery disease is the progressive plaque formation on the major arteries that can lead to heart failure. Nanomedicine can be utilized as a valid treatment because the development of the disease occurs at the cellular level. Current treatment of coronary artery disease chiefly consists of utilizing statins, known to have dose-dependent side effects which limit their application. Nanotechnology could produce targeted delivery of statins to the site of need, therefore reducing toxicity to other cells.
- Forokhzad, O.C. & Langer, R. 2009. Impact of Nanotechnology on Drug Delivery, American Chemical Society, 3, pp. 16-20. http://pubs.acs.org/doi/abs/10.1021/nn900002m
- National Cancer Institute- Benefits of Nanotechnology for Cancer. https://www.cancer.gov/sites/ocnr/cancer-nanotechnology/benefits
- Rajora, A.K. et al. 2014. Impact of the enhanced permeability and retention (EPR) effect and cathepsins levels on the activity of polymer-drug conjugates, Polymers, 6, pp. 2186-2220. http://www.mdpi.com/2073-4360/6/8/2186
- Azzopardi, E.A. et al. 2013. The enhanced permeability retention effect: a new paradigm for drug targeting in infection, Journal of Antimicrobial Chemotherapy, 68, pp. 257-274. https://www.ncbi.nlm.nih.gov/pubmed/23054997
- Ambesh, P. et al. 2017. Nanomedicine in coronary heart disease, Indian Heart Journal, 69, pp. 244-251. http://www.sciencedirect.com/science/article/pii/S0019483217301050