By Kristen Mulvihill
Scheie Vision Annual Report 2021
Physicians often use topical treatments such as eye drops to deliver drugs to the eye. While this is typically the most practical approach, a substance in tears can interfere with the drug delivery system (DDS) and drug absorption process.
DDS refers to the engineered technologies involved in transporting a therapeutic compound to its target site. A lipoplex is a common form of DDS found in ophthalmic medications. Considered the most effective DDS, lipoplexes serve many functions, including in gene therapy and chemotherapy.
Mucin, the deepest layer of the tear film, typically protects the eye. However, when mucin is exposed to certain molecules such as a lipoplex, it binds to the molecule and prevents the treatment from targeting the appropriate cells. When mucin binds to the lipoplex, only a minor fraction of the drug is efficiently absorbed and retained in the eye.
A team of researchers, including Mina Massaro-Giordano, MD, dry eye specialist at Scheie and Co-Director of the Penn Dry Eye and Ocular Surface Center, explored the interaction between lipoplexes and mucin to address this limitation and find a more effective method of ophthalmic drug delivery. Dr. Massaro is part of an international, multi-institutional collaboration between the Sbarro Institute for Cancer Research and Molecular Medicine at Temple University, the University of Pennsylvania’s Scheie Eye Institute, and several universities in Italy.
The researchers discovered that using an engineered, artificial protein coating (i.e. protein corona) to conceal the lipoplex improves ophthalmological drug uptake. The protein corona (PC) alters the physical and chemical properties of the DDS, providing an entirely new biological identity.
Specifically, researchers found that a coating comprised of a protein called fibronectin and a tripeptide of the amino acids valine, glycine, and aspartate was efficient in disguising the lipoplex and avoiding mucin interference. The artificial coronas were able to successfully reach and bind to the targeted tissue (i.e. corneal epithelial cells) for improved drug delivery and absorption.
“As a surface disease researcher and clinician, it is imperative to create drugs that will ‘sneak’ through the tear film and target the appropriate cells,” explained Dr. Massaro.
This study presents significant, novel opportunities for ocular drug delivery. The results have the potential to improve treatment options for a variety of ocular diseases and conditions.
“Dry eye is a very common problem and many novel molecules with diverse mechanisms are currently in clinical trials. However, these drugs will fail if delivery methods are not taken into consideration,” said Dr. Massaro. “Scientists must consider methods of ocular drug delivery in future research.”
References
Astarita C, Palchetti S, Massaro-Giordano M, Domenico MD, Petrillo F, Boffro S, Caracciolo G, Giordano A (2021) Artificial protein coronas enable controlled interaction with corneal epithelial cells: New opportunities for drug delivery. Pharmaceutics 13(867).