Precision medicine may lead to more effective treatments for ocular conditions

The most practical solution for drug delivery to the eyeball is topical, i.e. eye drops. However, a naturally occurring substance in tears actually can interact with the drug delivery system (DDS), hindering absorption of the drug and preventing it from getting into the cells it needs to target.

Mucin, or MUC, is usually there to protect your eye, but when MUC is exposed to a molecule such as a lipoplex, a common form of DDS already used in ophthalmological drugs, it will bind to it and reduce absorption into the targeted tissue. So, scientists asked, is there some way to sneak the lipoplex past the MUC?

Through the use of an engineered, artificial protein corona (PC), researchers were able to dress the lipoplexes up as something that MUC would ignore. They found that a protein called Fibronectin (FBN), and a tripeptide of the amino acids Valine, Glycine, and Aspartate (VGA), were both effective at concealing the lipoplex, avoiding being coated in MUC, and binding to the corneal epithelial cells for better absorption of the DDS.

Because MUC binds to the lipoplex surface, it alters both their size and the positive or negative surface charge. This reduces absorption of the medicine by the primary corneal epithelial cells. So, how do we prevent MUC from interfering? We give the liposome a new coating that is recognized by receptors expressed on the ocular surface, circumventing the problem, and delivering the molecule more directly to the targeted tissue."

Carlo Astarita, Ph.D. candidate studying at the Sbarro Institute for Cancer Research and Molecular Medicine, Department of Biology, College of Science and Technology, Temple University

The researchers are part of a multi-institutional, international collaboration between the Sbarro Institute for Cancer Research and Molecular Medicine at Temple University, the University of Pennsylvania's Scheie Eye Institute, and co-authors at several universities in Italy.

"As a dry eye specialist I see a myriad of patients with various surface disease issues," says Giacamina Massaro, M.D., of the Scheie Eye Institute, Department of Ophthalmology in the Perelman School of Medicine at the University of Pennsylvania, "and in order to achieve an effective treatment, drugs need to reach the target tissue (i.e. the corneal epithelial cells). In many situations the drugs are blocked by a complex mix of mucous, lipids, proteins and fluids which bathe the ocular surface. It is imperative that drugs have the ability to break through this barrier."

"This study is a quintessential example of our researchers using precision medicine to innovate," says Antonio Giordano, M.D., Ph.D., Founder and Director of the Sbarro Health Research Organization (SHRO) and the Sbarro Institute at Temple University, as well as a joint research program with the University of Siena, Italy. "We identify a problem which inhibits the efficacy of certain types of treatments, and then we ask, 'what does the body provide in this case as its own solution?' In this case, the answer is right there on the surface of the cells: we make the medicine so that it binds with the targeted tissue. In this way, precision medicine opens the door to increased effectiveness to treat a wide range of ocular conditions and disease."

Source:
Journal reference:

Astarita, C., et al. Artificial Protein Coronas Enable Controlled Interaction with Corneal Epithelial Cells: New Opportunities for Ocular Drug Delivery. Pharmaceuticals. doi.org/10.3390/pharmaceutics13060867.

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