Biology & Medicine News and Discussions

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New clues in fight against lethal bacteria
https://medicalxpress.com/news/2022-05- ... teria.html
by Australian National University

New research from The Australian National University (ANU) could lead to better treatment options for a rare but very lethal type of bacterial infection.

Professor Si Ming Man and his team say their latest research focuses on the family of bacteria that causes things like gangrene, sepsis and tetanus.

"While we understand a select few members of this family of bacteria, we were interested in what the others were doing to cause infection," Professor Man said.

"Thankfully, this group of bacteria is rare—less than 1,000 cases a year in the US.

"But one in particular we looked at for this study, Clostridium septicum, kills four out of five people who get it within two days. It's incredibly lethal."

The team discovered Clostridium septicum can rapidly kill cells by releasing a toxin that acts "like a hammer" punching holes in the surface of the cell.

This sends a danger signal to the immune system, but when our body swings into action it can actually cause more harm than good.

"The intention of the immune system is good—it's trying to fight against the bacteria—but the infected cells also explode and die," Professor Man said.

"When the bacteria spreads and you have lots of dying cells all over the body that's when it can lead to sepsis and shock. That is why patients die very rapidly."

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Respiratory syncytial virus accounted for more than 100,000 deaths worldwide in children under five during 2019
https://medicalxpress.com/news/2022-05- ... eaths.html
by Lancet

A new study published in The Lancet estimates that RSV-attributable acute lower respiratory infection was responsible for more than 100,000 deaths in children under five across the globe in 2019. The study is the first to examine RSV disease burden in narrow age brackets, reporting that there were over 45,000 deaths in infants under six months old in 2019, with one in five of the total global cases of RSV occurring in this age group.

"RSV is the predominant cause of acute lower respiratory infection in young children and our updated estimates reveal that children six months and younger are particularly vulnerable, especially with cases surging as COVID-19 restrictions are easing around the world and majority of the young children born in the last two years have never been exposed to RSV (and therefore have no immunity against this virus). With numerous RSV vaccine candidates in the pipeline, our estimates by narrower age ranges help to identify groups that should be prioritized, including pregnant people, so that children in the youngest age groups can be protected, similarly to current strategies which offer vaccines for whooping cough, typhoid, and tetanus to pregnant people," says Harish Nair, co-author of the paper, University of Edinburgh, UK.

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Intelligent Drug-Releasing Contact Lenses Could Help Treat Glaucoma

By Adrianna Nine on May 20, 2022 at 10:30 am
https://www.extremetech.com/extreme/335 ... t-glaucoma

A new type of contact lenses capable of detecting pressure build-up and releasing drug reserves could be used to treat glaucoma.

Glaucoma—which is technically a group of ophthalmic conditions—typically occurs in older adults and results in gradual vision loss, with some patients experiencing total blindness. The most common form of the condition is called open-angle glaucoma and begins when the patient’s drain structure (located at the inner corner of the eye) loses its effectiveness. This results in fluid build-up that increases pressure in the eye. The pressure damages the eye’s optic nerve and prevents the nerve from conveying visual messages to the brain.

Traditional treatments for glaucoma include prescription eye drops, oral medication, or surgery. The first two options work to reduce fluid creation in the eye, but both can result in an uncomfortable dry feeling and they increase the patient’s risk of heart or lung disease. Laser surgery, while increasing in popularity over recent years, is a riskier and more invasive procedure than some patients are comfortable with.

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First Human Trial of Experimental Cancer-Killing Virus Underway

By Adrianna Nine on May 20, 2022 at 10:17 am
https://www.extremetech.com/extreme/335 ... s-underway

Researchers at California’s City of Hope National Medical Center have created a virus that kills cancer cells, and its first human trial is officially underway.

The CF33-hNIS virus (referred to as Vaxinia) is an oncolytic virus, a genetically-engineered variety that habitually targets cancer cells while ignoring healthy cells. But beyond infecting and killing cancer cells, Vaxinia works overtime by delivering specially-engineered white blood cells, known as CAR T cells, to solid tumors. While CAR T cells are vital to helping the body’s immune system recognize cancer cells as a threat, solid tumors possess immunosuppressive microenvironments that act as barriers, preventing the CAR T cells from entering and doing their job. By infecting solid tumors, Vaxinia can deliver the CAR T cells to this environment and help the immune system tackle cancer the way it’s supposed to—all while proactively killing off cancer cells along the way.

[weatheriscool]

Genetic roots of three mitochondrial diseases identified via new approach
https://phys.org/news/2022-05-genetic-r ... roach.html
by Washington University School of Medicine

When something goes wrong in mitochondria, the tiny organelles that power cells, it can cause a bewildering variety of symptoms such as poor growth, fatigue and weakness, seizures, developmental and cognitive disabilities, and vision problems. The culprit could be a defect in any of the 1,300 or so proteins that make up mitochondria, but scientists have very little idea what many of those proteins do, making it difficult to identify the faulty protein and treat the condition.

Researchers at Washington University School of Medicine in St. Louis and the University of Wisconsin–Madison systematically analyzed dozens of mitochondrial proteins of unknown function and suggested functions for many of them. Using these data as a starting point, they identified the genetic causes of three mitochondrial diseases and proposed another 20 possibilities for further investigation. The findings, published May 25 in Nature, indicate that understanding how mitochondria's hundreds of proteins work together to generate power and perform the organelles' other functions could be a promising path to finding better ways to diagnose and treat such conditions.

"We have a parts list for mitochondria, but we don't know what many of the parts do," said co-senior author David J. Pagliarini, Ph.D., the Hugo F. and Ina C. Urbauer Professor and a BJC Investigator at Washington University. "It's similar to if you had a problem with your car, and you brought it to a mechanic, and upon opening the hood they said, 'We've never seen half of these parts before.' They wouldn't know how to fix it. This study is an attempt to define the functions of as many of those mitochondrial parts as we can so we have a better understanding of what happens when they don't work and, ultimately, a better chance at devising therapeutics to rectify those problems."

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Scientists identify how the brain links memories
https://medicalxpress.com/news/2022-05- ... ories.html
by University of California, Los Angeles

Our brains rarely record single memories—instead, they store memories into groups so that the recollection of one significant memory triggers the recall of others connected by time. As we age, however, our brains gradually lose this ability to link related memories.

Now UCLA researchers have discovered a key molecular mechanism behind memory linking. They've also identified a way to restore this brain function in middle-aged mice—and an FDA-approved drug that achieves the same thing.

Published in Nature, the findings suggest a new method for strengthening human memory in middle age and a possible early intervention for dementia.

"Our memories are a huge part of who we are," explained Alcino Silva, a distinguished professor of neurobiology and psychiatry at the David Geffen School of Medicine at UCLA. "The ability to link related experiences teaches how to stay safe and operate successfully in the world."

A bit of Biology 101: cells are studded with receptors. To enter a cell, a molecule must latch onto its matching receptor, which operates like a doorknob to provide access inside.

[Tadasuke]

>
Psilocybin Causes ‘Significant Reduction’ in Symptoms of Depression, Largest of its Kind Study Shows

https://hightimes.com/study/psilocybin- ... udy-shows/

"At the American Psychiatric Association (APA) 2022 Annual Meeting that began on May 21 in New Orleans, Louisiana, COMPASS Pathways unveiled the “largest randomized, controlled, double-blind study of psilocybin therapy ever completed,” according to a May 24 press release, and the data shows “significant” improvements to treatment-resistant depression (TRD) symptoms.

Participants were given a single dose of investigational COMP360 psilocybin, in doses of 25 mg or 10 mg, compared to 1 mg in patients with TRD. For the study, 233 patients with TRD received either 1 mg, 10 mg, or 25 mg COMP360 psilocybin, along with psychological support from therapists. Symptoms of depression were calculated using the Montgomery-Åsberg depression rating scale (MADRS).

The MADRS system has been used in the world of psychiatry since 1979 and measures apparent sadness (despondency, gloom), reported sadness, inner tension (discomfort, turmoil, dread), reduced sleep, reduced appetite, and concentration difficulty, typically in a ten-item questionnaire.

The people who received a 25 mg dose of COMP360 psilocybin with psychological support experienced a “highly statistically significant reduction in symptoms of depression after three weeks.” The difference between the group that received 25 mg and the group that received 1 mg was -6.6 on the MADRS depression scale at week three.

The effects also lasted very long—for three months, in some cases. The findings show that psilocybin provides “a rapid and durable response for up to 12 weeks.”

Twice the number of patients who received 25 mg (20.3%) had a “sustained response” at week 12, versus those who received 1 mg (10.1%). Tolerability and adverse effects were both reported mostly favorably, despite some reports commonly seen in people with TRD such as self-injury, but it was typically over a month after treatment."

Looks like psylocybin from psylocybin mushrooms is now proven to help with depression. I will ask my psychiatrist for it.

[wjfox]

NHS performs world’s first double hand transplant for scleroderma

Thu 26 May 2022 06.00 BST

A roof tiler whose hands were left unusable by an autoimmune disease has told of his joy after NHS surgeons successfully performed the world’s first double hand transplant for the condition.

Steven Gallagher was forced to stop working after scleroderma, a condition that scars the skin and internal organs, caused his hands to close up into a fist position. After first developing an unusual rash about 13 years ago, the condition then affected his nose and mouth, his fingers began curling in and he suffered “horrendous” pain.

But after undergoing a 12-hour operation at Leeds teaching hospital NHS trust – the first time anywhere in the world that hand transplantation has been used to replace hands terminally affected by scleroderma – he can turn on the tap and fill a glass of water for the first time in years. Gallagher, 48, is now hoping to return to work.

[...]

“When Prof Hart in Glasgow mentioned to me about a double hand transplant, at the time I laughed and thought that’s space-age kind of things … My wife and I spoke about it and came to the agreement to go for it. I could end up losing my hands anyway, so it was just a case of letting them know I was going to go with it.”

Prof Simon Kay, of Leeds teaching hospitals NHS trust, said the surgery was “a huge team effort” with as many as 30 health professionals involved.

https://www.theguardian.com/society/202 ... cleroderma



Photograph: Jane Barlow/PA

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Using a robotic shoulder to grow tendon tissue
https://medicalxpress.com/news/2022-05- ... issue.html
by Bob Yirka , Medical Xpress

A team of researchers from the University of Oxford and Devanthro GmbH has modified a robot shoulder to serve as a stretching mechanism in an effort to grow useful human tendon tissue. In their paper published in the journal Communications Engineering, the group describes modifying the robot shoulder and using it as a bioreactor to grow human tissue.

Over the past few decades, medical scientists have been investigating the possibility of using fibroblast cells to grow human tissue that can replace tissue lost or damaged in human patients. To that end, researchers have grown organs, skin, cartilage, and even a windpipe. But such endeavors are still in their infancy.

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Scientists solve long-standing mystery: Why do some asthma patients respond poorly to treatment?
https://medicalxpress.com/news/2022-05- ... ients.html
by Rutgers University

When taking medicine during an asthma attack, patients with the most severe form of asthma produce in their airways special substances that block the treatment from working, according to a study where Rutgers scientists collaborated with researchers at Genentech, a member of the Roche Group.

Reporting in the journal Science Translational Medicine, scientists said two different so-called growth factors—naturally occurring substances that stimulate cell proliferation—activate in the airways of severe asthma patients as they inhale corticosteroids used as an emergency treatment during an asthma attack.

The discovery was made as researchers investigated an enduring mystery in asthma treatment: Why do some patients who suffer the most from the disease often have the least success with conventional rescue treatments?

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New study reveals hundreds of new drug targets to combat tuberculosis
https://medicalxpress.com/news/2022-05- ... losis.html
by Rockefeller University

Tuberculosis is a stubborn disease, born of yet more stubborn microbes. While many bacterial infections resolve within days of starting antibiotics, tuberculosis often refuses to budge for around six months, and in some cases, may never release its vice grip on the human body. It claimed 1.5 million lives in 2020, second only to COVID-19 among infectious diseases.

Now, a new study in Nature Microbiology maps the methods by which Mycobacterium tuberculosis (Mtb) bacteria shrug off antibiotics, revealing hundreds of drug targets that could strip this pathogen of its notorious resistances. The scientists also identified a class of existing antibiotics that may be particularly effective against one prominent strain in Southeast Asia.

"Examining how current drugs affect bacterial physiology, and how the bacterium subverts this, is part of our long-term goal of developing better treatment combinations," says Rockefeller University's Jeremy Rock, head of Laboratory of Host-Pathogen Biology. "This study is the tip of the spear getting us into that realm."

A genome-wide view of Mtb

The researchers started out with a simple question. "We just wanted to know all of the genes involved in Mtb's resistance to different antibiotics," says Nick Poulton, a graduate student in Rock's lab and coauthor on the study. The team developed a platform based on the CRISPR gene knockdown tool that scoured the Mtb genome, pitting the bacteria against common antibiotics to quantify how the absence or presence of each gene impacted the efficacy of existing drugs.

[caltrek]

U.S. Health Outpaced by Other Countries, as Journal Looks for Root Causes
May 31, 2022

Introduction:

(EurekAlert) Health and mortality in the U.S. continue to rank poorly compared to peer nations, and a new supplemental issue to The Journals of Gerontology, Series B: Psychological Sciences and Social Sciences titled “Why Does Health in the U.S. Continue to Lag Behind?” features papers that analyze the reasons for the downward trends.

In 2010, according to the journal, life expectancy at birth in the U.S. was a full year lower than the average of 27 European Union countries; in the subsequent decade, the shortfall doubled, and the COVID-19 pandemic has widened the gap.

Even the most affluent U.S. states — those characterized by dynamic gig economies with many highly skilled workers — exhibit outcomes that are on par or lag national averages of other high-income countries. Chronic disease and disability levels are also generally higher in the U.S. compared to many other peer countries.

The supplemental issue was guest edited by Neil K. Mehta, PhD, of The University of Texas Medical Branch, Mikko Myrskylä, PhD, of the Max Planck Institute for Demographic Research, and the late Robert F. Schoeni, PhD, of the University of Michigan.

“There’s no simple answer,” Mehta said. “The issue touches on the many complicated factors with a focus on social and behavioral factors. The U.S. has lagged behind for some time, but over the last decade it’s gotten a lot worse. Even though the U.S. has fared poorly compared to other countries, we are falling even further behind.”

Read more here: https://www.eurekalert.org/news-releases/954447

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New type of triterpenes discovered
https://phys.org/news/2022-06-triterpenes.html
by University of Tokyo

A collaborative effort has revealed a new type of triterpene, a group of organic compounds which are an important source of many medicines. Until now, all triterpenes were believed to be derived from squalene, itself a type of triterpene. However, for the first time, researchers witnessed biosynthesis of triterpenes in fungi without the use of squalene. This important discovery opens up a whole new world of possibilities for pharmaceutical science.

Triterpenes are organic compounds which are abundantly found in animals, plants, microorganisms and even us. About 20,000 different triterpenes have been found and they are widely used in cosmetics, food supplements and, most importantly, medicine, thanks to their anti-inflammatory, anti-cancer, anti-diabetic and other valuable properties. Until now, all known triterpenes were thought to be generated from a common precursor or source, squalene.

However, as revealed in Nature, a collaborative effort among the University of Tokyo and KEK in Japan, Wuhan University in China and Bonn University in Germany, has found a new type of triterpenes that doesn't require squalene.

"Nobody could have imagined this happening in nature. This is the discovery of a new biosynthetic machine," explained Professor Ikuro Abe from the Graduate School of Pharmaceutical Sciences at the University of Tokyo.

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This parasite will self-destruct: Researchers discover new weapon against drug-resistant malaria
https://phys.org/news/2022-06-parasite- ... laria.html
by University of Melbourne

A new method to combat malaria, which sees the disease turn against itself, could offer an effective treatment for the hundreds of millions of people infected globally each year as the efficacy of current antimalarial drugs weakens.

The University of Melbourne-led research published today in Science has identified an anti-malarial compound, ML901, which inhibits the malaria parasite but does not harm mammalian—human or other mammals'—cells.

Co-lead author Professor Leann Tilley, from the Bio21 Institute at the University of Melbourne, said the ML901 compound effectively made the parasite the agent of its own demise, underpinning it potency and selectivity.

"ML901 works by an unusual reaction-hijacking mechanism," Professor Tilley said.

"Imagine a stealth weapon that can be used to launch a self-destruct attack on your vehicle—slamming on the brakes and cutting the engine. ML901 finds a particular chink in the machinery that the malaria parasite uses to generate the proteins needed to reproduce itself and stops it doing so.

"While there is much work to be done to fine-tune what we've discovered, these results are really encouraging in the search for new antimalarials."

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Repurposing cancer drug to treat neuroinflammation
https://medicalxpress.com/news/2022-06- ... ation.html
by Karolinska Institutet

The repurposing of FDA-approved drugs for alternative diseases is a faster way of bringing new treatments into the clinic. Researchers at Karolinska Institutet in Sweden have repurposed a cancer drug for treatment of neuroinflammatory diseases such as multiple sclerosis. A novel drug carrier was also developed to facilitate drug delivery to target myeloid cells. These pre-clinical findings are described in a paper in the journal EMBO Reports.

Microglia are an organ-specific type of macrophage in the central nervous system. In the majority of chronic neurodegenerative disease conditions, such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease and chronic multiple sclerosis (MS), dysfunctional microglia play an important role. Modifying the activation of these disease-promoting microglia is an attractive therapeutic principle.

"The biotechnology industry has realized the potential for microglia-targeting strategies, and at least 20 new companies have started during recent years," says Professor Bob Harris at the Center for Molecular Medicine, Karolinska University Hospital and the Department of Clinical Neuroscience, Karolinska Institutet. "Compared to novel drug discovery programs that can take 20 years before a new medicine is approved, using existing prescribed drugs can halve that time."

The researchers used in silico drug screening to identify candidates for microglial modulation and selected a Topoisomerase 1 (TOP1) inhibitor for further study. TOP1 was highly expressed in neuroinflammatory conditions both in mice and in tissues from MS patients, and TOP1 inhibition using camptothecin (CPT) and its FDA-approved analog topotecan (TPT) reduced inflammatory responses in microglia and macrophages in in vitro cultures, as well as ameliorating neuroinflammatory diseases in vivo.

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Researchers find epigenetic changes during pregnancy may contribute to the development of asthma

by University of Chicago Medical Center
https://medicalxpress.com/news/2022-06- ... sthma.html

Asthma is a chronic condition that affects 25 million people in the United States. Having a mother with asthma is an important risk factor and a new study may explain why. A team of researchers at the University of Chicago have found striking epigenetic differences in the airway cells of patients with asthma who have asthmatic mothers, compared to patients whose mothers never had asthma. The research was published on June 6 in Proceedings of the National Academy of Sciences.

Carole Ober, Ph.D., and her research team have spent years examining genetic influences that contribute to the development of asthma, including epigenetic factors. Epigenetics refers to changes in how genes are expressed that are not directed by changes or mutations in the DNA sequence itself. Instead, gene activity can be turned on or off by the attachment of small chemical structures such as methyl groups to DNA. Many environmental factors are known to impact DNA methylation patterns, including the in-utero environment.

In the study, the team found different DNA methylation patterns in epithelial cells of the lower airways of asthmatic adults with asthmatic mothers compared to those whose mothers did not have asthma.

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Stem cell research reveals detailed genetic roadmap of glaucoma
https://medicalxpress.com/news/2022-06- ... admap.html
by University of Melbourne

A new, detailed genetic roadmap of glaucoma—the world's leading cause of irreversible blindness—will help researchers develop new drugs to combat the disease, by identifying potential target areas to stall or reverse vision loss.

The research, one of the largest and most detailed stem cell modeling studies reported for any disease, is published today in Cell Genomics.

By comparing stem cell models of the retinal ganglion cells of people with Primary Open Angle Glaucoma to those without the disease, more than 300 novel genetic features of these cells were uncovered.

The findings are the result of a national collaboration led by Professor Alex Hewitt (Centre for Eye Research Australia, University of Melbourne and University of Tasmania), Professor Alice Pébay and Dr. Maciej Daniszewski (University of Melbourne) and Ms Anne Senabouth and Professor Joseph Powell (Garvan Institute of Medical Research).

Professor Hewitt, who is Head of Clinical Genetics at CERA, says the study will lead to a better understanding of the mechanisms that damage retinal ganglion cells and lead to the onset of glaucoma.

[weatheriscool]

Rapid Ebola diagnosis may be possible with new technology
https://medicalxpress.com/news/2022-06- ... ology.html
by Washington University School of Medicine

A new tool can quickly and reliably identify the presence of Ebola virus in blood samples, according to a study by researchers at Washington University School of Medicine in St. Louis and colleagues at other institutions.

The technology, which uses so-called optical microring resonators, potentially could be developed into a rapid diagnostic test for the deadly Ebola virus disease, which kills up to 89% of infected people. Since it was discovered in 1976, Ebola virus has caused dozens of outbreaks, mostly in central and west Africa. Most notable was an outbreak that began in 2014 and killed more than 11,000 people in Guinea, Sierra Leone and Liberia; in the U.S., the virus caused 11 cases and two deaths. A rapid, early diagnostic could help public health workers track the virus' spread and implement strategies to limit outbreaks.

The study—which also involved researchers from the University of Michigan, Ann Arbor, and Integrated Biotherapeutics, a biotech company—is published June 8 in Cell Reports Methods.

"Any time you can diagnose an infection earlier, you can allocate health-care resources more efficiently and promote better outcomes for the individual and the community," said co-first author Abraham Qavi, MD, Ph.D., a postdoctoral researcher at Washington University. "Using a biomarker of Ebola infection, we've shown that we can detect Ebola infection in the crucial early days after infection. A few days makes a big difference in terms of getting people the medical care they need and breaking the cycle of transmission."

[weatheriscool]

New drug delivery system releases therapeutic cargo only when bacteria are present
https://phys.org/news/2022-06-drug-deli ... teria.html
by Kevin Stacey, Brown University

A team of Brown University researchers has developed a new responsive material that is able to release encapsulated cargo only when pathogenic bacteria are present. The material could be used to make wound dressings that respond quickly to burgeoning infections, but only deliver medication on demand.

The development is particularly relevant in the face of the global antibiotic resistance crisis, the researchers say, as the material could help to fight infections while also addressing the problem of resistance.

"We've developed a bacteria-triggered, smart drug-delivery system," said Anita Shukla, an associate professor in Brown's School of Engineering, who led the material's development. "Our hypothesis is that technologies like this, which reduce the amount of drug that's required for effective treatment, can also reduce both side effects and the potential for resistance."

The new material, described in the journal ACS Applied Materials and Interfaces, is a hydrogel—a hydrated polymer network. Hydrogels are highly biocompatible, and can be used to encapsulate a range of nanoparticles or small molecule therapeutics. They are often used in wound dressings. "Smart" or responsive hydrogels are emerging as promising platforms for drug delivery. They can be made to respond to the localized environment—speeding or slowing the release of medication in response to temperature, pH or other factors.

[weatheriscool]

New delivery method allows slow-release of broader array of peptide drugs in the body
https://phys.org/news/2022-06-delivery- ... array.html
by University of Michigan

A new study from the University of Michigan describes one of the first entirely new drug delivery microencapsulation approaches in decades.

Microencapsulation in biodegradable polymers allows drugs such as peptide therapeutics to be released over time in the body.

Peptides are molecules in the body that are composed of short chains of amino acids, and include messengers, growth factors and well-known hormones such as insulin. Because of their larger size and structure, peptide drugs are rarely given by mouth and must be injected. Microencapsulation is one way to decrease the time needed between injections.

One slow-release delivery method for peptide drugs is to encapsulate them within the type of resorbable polymers often used as dissolving sutures, said study co-author Steven Schwendeman, professor of pharmaceutical sciences and biomedical engineering.

However, development of polymer dosage forms for delivery of certain peptide drugs has been difficult because the currently available methods to microencapsulate the peptide molecules in the polymer require organic solvents and complex manufacturing.

"The Schwendeman group discovered about 10 years ago that peptides can bind and enter the polymer spontaneously from water to microencapsulate the peptide very simply without organic solvent," Schwendeman said.