黑料百科

Patricia LiWang was at an impasse.

It was 2011 and the 黑料百科 professor鈥檚 research group had figured out how to make some of the most potent HIV inhibitors even more powerful. LiWang was thrilled by these findings; funding agencies like the National Institutes of Health (NIH) weren鈥檛.

鈥淥ur primary interest was working on making better and better HIV inhibitors,鈥� LiWang said. 鈥淭he NIH wasn鈥檛 interested in more powerful inhibitors. They asked us 鈥榃hy aren鈥檛 you working on getting this into people?鈥� But there are problems with getting this into people.鈥�

LiWang鈥檚 inhibitors are proteins, and protein-based medicines don鈥檛 make for effective pills. The problem isn鈥檛 the pill, per se. The problem is the digestive tract.

The digestive tract is alive with enzymes, many of which exist to break down proteins. This is why, for example, there鈥檚 no insulin pill. Insulin, also a protein, is only effective when administered in ways that bypass these protein-destroying enzymes. That鈥檚 why insulin is usually injected. Swallow it, and it won鈥檛 work. LiWang鈥檚 HIV inhibitors are no different.

LiWang needed an alternative delivery system. Topical use 鈥� i.e., an insertable film to prevent the sexual spread of HIV 鈥� seemed the best bet, but then a second problem arose.

Protein-based medicines tend to degrade unless handled carefully. Refrigeration is key; anything warmer, and the medicine loses potency. That鈥檚 a non-starter for an HIV drug, which must remain effective in parts of the world where access to climate-controlled storage is limited.

LiWang was stuck. She had developed powerful drugs capable of thwarting HIV, albeit in a controlled laboratory setting. But she had no way to administer or stabilize the drugs for long-term storage and use.

Enter .

Kaplan鈥檚 group studies biomaterials at Tufts University. While working with fibroin, a protein found in silk, they discovered something remarkable: fibroin stabilizes proteins without the need for refrigeration. Equally intriguing was the possibility that fibroin capsules or films could provide a system for topical delivery of HIV inhibitors.

鈥淒avid had a paper about stabilizing the measles, mumps and rubella (MMR) vaccine in silk,鈥� LiWang said. 鈥淚 emailed and said we were trying to stabilize our molecule. But ours would be for topical use. I told him that his stuff would be perfect for us.鈥�

The collaboration began in 2013 and proved immediately fruitful. By 2014, the formerly indifferent NIH awarded LiWang and her collaborators a four-year, $2.3 million grant to support the work. And now that work is coming to fruition.

The team recently published a paper in the journal ACS Biomaterials 鈥� 鈥溾�� 鈥� showing that they can create a silk-based system that can store, stabilize and topically administer protein-based HIV inhibitors.

With many effective options already on the market, new HIV inhibitors aren鈥檛 always big news. But this is more than just a new inhibitor 鈥� it鈥檚 a new delivery system. And it may solve some of lingering problems associated with HIV prevention.

LiWang and her collaborators show that their silk-stabilized inhibitors remain effective for over a year at temperatures as high as 122 degrees Fahrenheit. While other drugs would be vulnerable to temperature spikes, LiWang鈥檚 inhibitors remain potent in almost any environment. For areas like sub-Saharan Africa, where those most susceptible to infection have limited access to refrigeration, this feature is key.

Another issue with existing HIV drugs relates to dosing regimens. Most of the available drugs require daily use, but studies indicate that many at-risk populations can鈥檛 adhere to this schedule. LiWang鈥檚 silk-protein system offers a solution. It replaces the daily pill with a film that can be inserted and then remain effective for a month.

LiWang cautions that her team鈥檚 new system is not yet clinic-ready. A few more hurdles remain.

The silk-protein system needs to be tested on primates before it can be tested on humans. at the is working with LiWang to test the system in macaques. If it proves safe and effective, human trials would follow.

LiWang hopes her system will be the 鈥渙ne in a hundred鈥� that makes it to human trials because she鈥檚 convinced it has the potential to help people most at risk for HIV in resource-poor regions of the world.

鈥淲e鈥檙e purposely working with proteins that can be made affordably,鈥� LiWang said. 鈥淭his is not going to help a drug company鈥檚 bottom line, but it might help prevent the spread of HIV in the developing world.鈥�