Nanoparticle-based delivery systems may be useful in delivering medications in autoimmune and rheumatic diseases. A recent study published in the April edition of The Journal of Clinical Investigation reports on the results of administering mycophenolic acid (MPA) via a nanoparticle formulated with a gel interior in a mouse model of systemic lupus erythematous.1
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“Some drugs have systemic toxic side effects associated with their current method of administration,” said lead author Michael Look, PhD, a postdoctoral fellow in the Fahmy Laboratory at Yale University in New Haven, Conn. “Using nanogel delivery is possibly a new way to deliver drugs at much lower doses and with less toxicity by focusing delivery to the areas in the body that are diseased and problematic.”
The researchers developed a nanoparticle with a biodegradable gel-like core enclosed in a lipid bilayer. This resulted in a nanogel resembling of two other types of Food and Drug Administration–approved platforms, liposomes and polymer matrices, with the favorable features of both. Nanoparticles loaded with MPA were administered weekly to New Zealand black/New Zealand white F1 mice (NZB/W F1) between 18 to 20 weeks of age until a survival endpoint was reached. Equivalent doses administered in saline provided no benefit.
Increase in Mean Survival Time
Nanogel treatment targeted toward CD4 cells increased mean survival time (MST) by three months when used prophylactically (MST 50 weeks vs. 38 weeks without treatment, P<0.0083). MST increases of two months were seen when treatment began after development of proteinuria (12.5 weeks vs. four weeks in the nontreatment group (P<0.0198).
CD4 targeted nanogels were therapeutically similar to the nontargeted formulations. There was also a reduction seen in inflammatory cytokines such as interleukin 12 and interferon gamma.
Lower Dose, Less Toxicity
“We found that nanoparticle therapy can be used to enhance conventional regimens, they are very potent, and can deliver therapeutically significant levels of drugs at much smaller doses than other delivery methods,” says Tarek Fahmy, PhD, senior author and professor of biomedical engineering at Yale. “Our results open the possibility that medications can be given at lower doses and frequencies resulting in fewer toxicities.”
This ability of nanogels to lower dosages needed to treat diseases may also serve to widen the number of available therapies.
“There are a number of promising compounds that were abandoned because they were viewed as being too toxic,” notes Dr. Fahmy. “Nanogels may allow us to revisit some of these options.”