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Institute for Stem Cell Biology and Regenerative Medicine (inStem), Bengaluru has designed and tested a new drug delivery system to treat diseases resulting from chronic inflammation. The researchers used a cationic lipid-based delivery system which resulted in high treatment outcomes.
The scientists have gained new insights about immune reactions caused by damaged cells leading to chronic inflammation resulting in osteoarthritis, rheumatoid arthritis, Crohn’s disease and fibrosis.
Srikala Raghavan along with Praveen K. Vemula, Srujan Marepally, Samarth Hegde, Ambika S. Kurbet and Oindrila Bhattacharjee studied how the loss of a protein called beta integrin 1 from skin cells causes wide-spread inflammatory reaction without the presence of invasive germs. The double-edged sword of inflammation, which is the immune system’s first line of defense against infection, turns its destructive force onto the very body it is supposed to protect, they said.
In a collaborative effort with Vemula’s group, also led to the development and testing of a new transdermal drug delivery system to combat chronic inflammation.
Beta integrin 1 is an essential protein on the cell surface that is involved in regulating cell shape, movement and cell reproduction. Raghavan’s team show that the loss of this molecule in the skin cells of mice results in a massive cascade of inflammatory signals that begin to recruit large numbers of immune cells. These eventually distort the skin’s basement membrane. However, despite widespread disarray in the basement membrane, the skin barrier remains intact.
“What is really unique about our model is that barrier formation is completely intact in animals because of their strong immune response. It also indicated that the source of the inflammatory response is not external. This makes it an ideal model to study sterile inflammation. Working out the inflammatory response from the loss of beta integrin 1 and proving that we could alleviate this inflammation with drugs was exciting,” stated Raghavan.
However, the immune reaction and inflammation in such mice begins to build up during the embryo phase. Therefore, treating inflammation with drugs was a big challenge. “We took up the challenge to develop a localised drug delivery vehicle to release the medication transdermally,” said Vemula.
“Typically, cationic molecules with a positive charge fuse with skin and can deliver cargoes inside skin. That is why we used a cationic lipid-based delivery system. What really got us excited was the efficiency of the drug delivery. We were hoping it would work, and expected only about 10 to 20% drug delivery. The efficiency was so high, that the treatment outcomes were visible,” he added.
The results obtained by Raghavan’s and Vemula’s groups have been published as a paper titled ‘Sterile Inflammation Enhances ECM Degradation in Integrin ß1 KO Embryonic Skin’ in the journal Cell Reports in September 2016.
“Our tie-up with Vemula ensured that we were able to deliver drugs to treat inflammation at the right place, right time and at the right dose in a set of non-standard experiments,” said Srikala.
“Understanding the signals in sterile inflammation will be critical to develop targeted therapies for chronic inflammation,” said Kurbet and Hegde, the lead authors of the research paper.
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