Category: Research

State approves nation’s first Ph.D. program in pharmaceutical engineering

Pharmaceutical engineering and sciences make up key components of the $1.2 trillion pharmaceutical industry. (Image: Getty)
Greg Weatherford
VCU School of Pharmacy
(804) 828-6470

Virginia Commonwealth University will be home to the nation’s first Ph.D. program in pharmaceutical engineering.

The doctoral program, a collaboration between VCU’s School of Pharmacy and College of Engineering, will focus on research and training students in areas of drug product development such as continuous manufacturing and drug-containing nanomaterials. 

VCU received formal notice of the program’s approval  by the State Council of Higher Education for Virginia (SCHEV). 

“As a nationally prominent research institution, VCU is proud to lead the next wave of pharmaceutical innovation,” said VCU President Michael Rao, Ph.D. “I am grateful to SCHEV for its support of this program and for recognizing how it can benefit the commonwealth and the world.” 

The doctoral program will start its first class in the fall of 2020. Its multidisciplinary curriculum will offer students unique professional development opportunities and will cover advanced topics in the field, experimental techniques, and scientific integrity, along with extensive directed and independent cross-disciplinary research. 

“Our mission is to provide a student-centric, collaborative and team-based experience for our students. We will prepare the future generation of science and engineering leaders who can act in the pharmaceutical industry as well as in regulatory areas and academic settings,” said Sandro da Rocha, Ph.D., director of the Center for Pharmaceutical Engineering and Sciences in the School of Pharmacy and professor of pharmaceutics. “By training scientists in better delivery systems and new medicines and therapies, we intend to find ways to treat complex diseases, even ones that have been considered untreatable.”

Pharmaceutical engineering and sciences make up key components of the $1.2 trillion pharmaceutical industry. It is a convergent branch of science and engineering that uses a cross-disciplinary approach to design, develop and manufacture pharmaceutical products. Some examples include:

  • Applying materials science and engineering to the development of drug delivery carriers and devices
  • Applying nanoscience and nanotechnology to medicine
  • Developing new technologies for the manufacture of chemicals and biologically active ingredients
  • Using computer science and engineering to model processes, harvest and analyze data for the design, discovery and manufacture of active ingredients  
  • Using engineering and physiology for the development of new devices and formulations 
  • Designing and manufacturing novel formulations for specific delivery profiles  

“The doctoral program in pharmaceutical engineering continues VCU’s advance to a nationally recognized hub for entrepreneurial research and drug delivery, development and manufacturing,” said Thomas D. Roper, Ph.D., the center director in the College of Engineering and a professor of chemical and life-science engineering.

Historically, investment in the development of new medicines has focused on research more than on product delivery and manufacturing. In recent years, however, the United States Food and Drug Administration has encouraged innovations in delivery systems such as nanomedicine and improvements in manufacturing processes to help ensure that patients get the medicines they need safely and effectively. 

“The VCU School of Pharmacy has always prepared professionals for the health care needs of the future,” said Joseph T. DiPiro, Pharm.D., dean of the pharmacy school and Archie O. McCalley chair. “This new Ph.D. program supports that mission, and cements VCU’s status as a groundbreaker in health-related education in ways that have visible and powerful effects on our communities.” 

Barbara D. Boyan, Ph.D., the Alice T. and William H. Goodwin Jr. dean of the College of Engineering, said, “With the creation of the pharmaceutical engineering Ph.D. program, VCU is seeking to become a national leader in the education of the pharmaceutical workforce of today and innovators leading future developments. The program will address the growing need for a new generation of researchers trained in cross-disciplinary and interdisciplinary science who recognize the need for a team-based approach to solving challenges related to the design and manufacturing of pharmaceutical products.” Learn more about the Center for Pharmaceutical Engineering and Sciences here.

Zhu designs drug delivery systems to test nanovaccines for brain and skin cancer

Guizhong Zhu, Ph.D., holds several grants to support studies on nanovaccines for glioma, a tumor of the brain and spinal cord, and melanoma, the deadliest form of skin cancer.
By Blake Belden

Having a research laboratory on a medical campus, Guizhi Zhu, Ph.D., will often cross paths with cancer patients, and it’s during those instances that he is most driven to continue his work.

“I sometimes feel helpless because I can’t do much for them in that moment other than saying some kind words,” he said. “Those are the moments that help me focus on my research to potentially have an impact that can change or improve therapeutic outcomes for cancer patients.”

Guizhi “Julian” Zhu uses innovative drug delivery platforms to test the efficacy of novel immunotherapeutics for a variety of disease types including skin, liver, brain, colorectal and breast cancers.

He joined VCU Massey Cancer Center as an associate member of the Developmental Therapeutics research program in 2018, and he is an assistant professor in the Department of Pharmaceutics and Center for Pharmaceutical Engineering and Sciences at the VCU School of Pharmacy.

Leveraging an extensive background in engineering, chemistry and pharmacology, Zhu designs targeted drug delivery systems and develops cancer nanomedicines such as nucleic acid nanovaccines for enhanced therapeutic benefit. Nanovaccines are vaccines that dispense microscopic particles into the immune system to stimulate a response against cancer cells, and they hold promise for treating disease more effectively than existing vaccines. Zhu tests a variety of nucleic acids, including immunomodulatory DNA/RNA, gene-expression modulation DNA/RNA, drug-encoding mRNA or gene-editing nucleic acids.

Zhu currently holds several grants to support studies on nanovaccines for glioma, a tumor of the brain and spinal cord, and melanoma, the deadliest form of skin cancer.

Under the mentorship of Steven Grossman, M.D., Ph.D., deputy director of Massey, Zhu holds an American Cancer Society Institutional Research Grant (ACS-IRG) to study the combination of an immunotherapy and an immuno-activating chemotherapy to treat melanoma.

He is also one of the principal investigators , together with Kristoffer Valerie, Ph.D., and Paula Bos, Ph.D., members of the Cancer Molecular Genetics research program at Massey, on a Massey Pilot Project that will explore the combination of a nanovaccine, immune re-energizing drugs and radiation therapy to treat glioma in mouse models.  

“This project is really exciting because there isn’t a durably effective treatment option for glioma,” Zhu said. “We hope that by using radiation we can jump start the tumor microenvironment to make immunotherapy more effective.”

He is a KL2 Mentored Clinical Research Scholar under the mentorship of Douglas Sweet, Ph.D., and Sandro da Rocha, Ph.D., an Endowment Fund awardee from the VCU Wright Center for Clinical and Translational Research and a VCU Presidential Research Quest Fund recipient.

Zhu leads a research team of six postdocs and graduate students as well as multiple undergraduate students and visiting scholars.

He grew up in China where he earned a bachelor’s degree in biotechnology from Nankai University. Zhu moved to the United States, where he earned his Ph.D. in medical science – physiology and pharmacology – and also completed a postdoctoral fellowship in cancer nanomedicine at the University of Florida. He finished a second postdoctoral fellowship in cancer immunotherapy and bioimaging from the National Institute of Biomedical Imaging and Bioengineering in Maryland. During this time, Zhu collaborated in famous and well-established laboratories to engineer and image nanomedicines. It was following this fellowship when he centered his work around cancer immunotherapies.

“Because the nature of my work is heavily focused on cancer immunotherapy, the scientific combination of pharmaceutics and cancer offers an ideal environment for me at Massey,” Zhu said.

Zhu has published more than 70 articles in peer-reviewed journals, including Nature Communications, Proceedings of the National Academy of Sciences, Journal of the American Chemical Society, ACS NanoAngewandte Chemie, among others. His publications have been cited by peers more than 4,500 times in the past five years, according to Google Scholar. Zhu is a member of the American Chemical Society, the Oligonucleotide Therapeutics Society and the Society for Immunotherapy of Cancer. He received a Distinguished Scientist Award from the National Institutes of Health in 2017, and he was awarded the Alan M. Gewirtz Memorial Fellowship by the Oligonucleotide Therapeutics Society (2013), among other awards.

Zhu lives with his daughter and mother in Richmond, and they await the arrival of his wife who is close to finishing her doctoral degree in food science and nutrition in Maryland.

VCU team explores epigenetics as cause of adverse drug reactions in elderly

A photo of an old person's hand with a hospital wrist band being held by a younger person's hand.
Older patients are almost seven times as likely to be hospitalized for drug reactions than younger ones. Researchers from VCU’s pharmacy and medical schools are examining the role of epigenetics.

Greg Weatherford
Director of Communications
VCU School of Pharmacy

A VCU School of Pharmacy research team is studying how aging affects the ways drugs interact with the body. The results may help doctors better manage medications in older patients. 

The aim is to better understand why older people seem to metabolize drugs more slowly, with the goal of someday seeing fewer adverse drug reactions and hospitalizations among the elderly, said the principal investigator, Joseph McClay, Ph.D., an assistant professor in the VCU School of Pharmacy’s Department of Pharmacotherapy and Outcomes Science. 

Older patients are almost seven times as likely to be hospitalized for adverse drug reactions than younger ones, according to a 2006 study in the Journal of the American Medical Association. A separate study in the United Kingdom found that adverse drug reactions contributed to 6.5% of hospital admissions and primarily occurred in older patients.

The causes for these disparities are not well known, McClay said. 

The study, supported by a $454,000 grant from the National Institute on Aging, will explore how genetic factors that are turned on and off by the body — a process known as epigenetics — affect how the body interacts with medications as it ages. 

The body’s genes, its DNA, do not change over time. But its epigenetics, how the body expresses those genes, does. The VCU team will begin the process of tracking how these epigenetic changes affect the body’s reaction to drugs. 

McClay and his colleagues — Elvin Price, Pharm.D./Ph.D., and Matthew Halquist, Ph.D., in the VCU School of Pharmacy and Mikhail Dozmorov, Ph.D., and Patrick Beardsley, Ph.D., in the VCU School of Medicine — and a team of graduate students will begin by mapping age-related changes in key genes using samples of livers from aged mice from the National Institute on Aging. 

This map of epigenetic changes, McClay said, will help researchers understand how the liver, the body’s main organ for metabolizing drugs and other outside chemicals, could interact with medicines in older bodies. 

Once the mapping is complete, the team plans to focus on a gene known as CYP2E1, which is part of the liver’s system of metabolizing chemicals such as drugs and alcohol and has been shown by the VCU team and others to be expressed differently in older bodies. 

In particular, the VCU researchers will study how chlorzoxazone, a drug metabolized by CYP2E1, is affected. If livers from older mice metabolize the drug more slowly, as McClay and his team predict, this could lead to greater understanding of the reasons that older humans are affected differently by medications. and iIn time this could lead to better medication dosing in elderly patients.

“That is the point, in the end,” McClay said. “We want to keep people healthy.” 

VCU creates Center for Pharmaceutical Engineering and Sciences

Four people stand in a row, smiling at the camera.
The center’s two directors, Sandro da Rocha, Ph.D., and Thomas D. Roper, Ph.D., pose with Barbara D. Boyan, Ph.D., dean of the College of Engineering, and Joseph T. DiPiro, Pharm.D., dean of the School of Pharmacy.

By Kendra Gerlach
VCU College of Engineering
(804) 827-0631
kegerlach2@vcu.edu

Virginia Commonwealth University has opened a Center for Pharmaceutical Engineering and Sciences. The new interdisciplinary center, one of few in the country and the only one of its kind in Virginia, is a collaboration between the university’s School of Pharmacy and College of Engineering. It will focus on researching, creating and patenting drug products and pharmaceutical processes that can address future health needs of society.

Pharmaceutical engineering and sciences is a field that covers all aspects of drug product design — from drug discovery and preclinical studies to manufacturing, formulation and packaging — and spans various areas including chemical, mechanical and biomedical engineering as well as pharmaceutical sciences, chemistry and materials science. The field is a key component of the $1.2 trillion pharmaceutical industry.

“This new center brings together not only two schools but many areas of expertise across VCU,” said Joseph T. DiPiro, Pharm.D., dean of the School of Pharmacy and Archie O. McCalley Chair. “Working with researchers and industry partners, VCU’s Center for Pharmaceutical Engineering and Sciences will discover and deliver health products that improve and save lives.”

“VCU’s Center for Pharmaceutical Engineering and Sciences will help address the growing need for a new generation of researchers trained in cross-disciplinary and interdisciplinary science and engineering who see the need for a team-based approach to solving challenges related to the design and manufacturing of pharmaceutical products,” said Barbara D. Boyan, Ph.D., the Alice T. and William H. Goodwin Jr. Dean of the College of Engineering.

The center has four main goals:

  • Facilitate multidisciplinary research and educational and entrepreneurial efforts in the field.
  • Promote a state-of-the-art infrastructure core for the development of pharmaceutical products.
  • Partner with and provide service to industrial and other stakeholders.
  • Serve the community in the region, the commonwealth of Virginia and nationwide.

“The Center for Pharmaceutical Engineering and Sciences will affirm VCU’s place among the nation’s hubs for entrepreneurial research and drug delivery, development and manufacturing,” said Thomas D. Roper, Ph.D., center co-director and a professor of chemical and life science engineering in the College of Engineering.

“By creating a center in which our scholars and experts in various areas can work collaboratively to develop innovative treatments, VCU is putting into action its principles of improving health and investing in research that can make a difference in people’s lives,” said Sandro R.P. da Rocha, Ph.D., co-director of the center and a professor in the Department of Pharmaceutics in the School of Pharmacy.

Both the School of Pharmacy and the College of Engineering have successful records in research. The College of Engineering recorded $18.2 million in sponsored research in 2018; last year the college received $2.2 million from the U.S. Defense Advanced Research Projects Agency to support its Pharmacy on Demand initiative. The School of Pharmacy is No. 15 in the nation for research funding from the National Institutes of Health and brought in $9.85 million in research funding last year.

Medicinal Chemistry ranked as top VCU department for inventions

 

Two men face the camera, shaking hands. One holds a plaque.
Martin Safo is the No. 1 inventor at the top-ranked department at VCU for invention disclosures. In this file photo he poses with VCU President Michael Rao, left, at the 2014 VCU invention awards.

Greg Weatherford
Director of Communications
VCU School of Pharmacy

The No. 1 department at VCU for invention disclosures in 2018 was the School of Pharmacy’s Department of Medicinal Chemistry, according to the latest annual report from VCU’s Innovation Gateway.

With 12 faculty members, the Medicinal Chemistry Department reported 14 inventions last year. That figure comprised more than 10% of the  university’s overall 134 invention disclosures for 2018.

“This is the latest recognition of the groundbreaking work going on at the School of Pharmacy,” said Joseph T. DiPiro, dean of the School of Pharmacy and Archie O. McCalley chair. “Under the leadership of Dr. Umesh Desai, our Medicinal Chemistry Department continues to demonstrate the importance of innovation. Pharmacy has always been about innovation and discovery, and these creative researchers are finding new ways to treat diseases.”

With five inventions credited, professor Martin Safo, Ph.D., was the department’s No. 1 for disclosures. His research has focused on finding ways to improve the health of people with sickle-cell disease and those who have difficulty absorbing vitamin B6 because of a hereditary disorder that can cause severe disabilities in children.

“Our work has the potential to improve the lives of millions around the world,” Safo said. “I’m proud to play a role in moving health science forward at the School of Pharmacy and at VCU.”

Also highlighted in the annual report is Shijun Zhang, Ph.D., an associate professor in medicinal chemistry, for his work designing a compound that can reduce inflammation in nerve tissues, a key symptom and risk factor of Alzheimer’s and other neurodegenerative disorders.

Four VCU departments ranked second for invention disclosures with 12 each in 2018: chemistry, electrical/computer engineering, computer engineering, chemical/life science engineering and mechanical/nuclear engineering.

When tallied by school or college, VCU School of Medicine reported the most invention disclosures with 53, followed by the VCU College of Engineering with 43, the College of Humanities & Sciences with 24, and the School of Pharmacy with 15. 

Innovation Gateway, part of VCU’s Office of Research and Innovation, releases its report on invention, commercialization and research each year. See the full 2018 report: https://innovationgateway.vcu.edu/media/innovation-gateway/docs/annual-reports/VCUIG_2018_Annual_ReportWEB.pdf

In clearest view ever of cell membrane, VCU team finds unexpected structure and new areas for pharmaceutical research

An illustration of a cell membrane.
An illustration of a cell membrane. (Getty)

Greg Weatherford
VCU School of Pharmacy
Director of Communications

Working with a Nobel Prize-winning biophysicist, a team of researchers at Virginia Commonwealth University has used an innovative technique to gain the clearest view yet of a patch of cell membrane and its components, revealing unexpected structures and opening up new possibilities for pharmaceutical research.

Cell membranes are formed largely of a bimolecular sheet, a fraction of the thickness of a soap bubble, in which two layers of lipid molecules are packed with their hydrophobic tails pointing inward and their hydrophilic heads outward, exposed to water.

The internal shape and structure of this lipid bilayer have remained largely mysterious after almost a century of research. This is in large part because most methods to examine membranes use detergents, which strip away the lipids that make up much of the membranes’ structures.

In a newly published paper in Proceedings of the National Academy of Sciences of the United States of America, the team — led by Youzhong Guo, Ph.D., of the Virginia Commonwealth University School of Pharmacy — used a new detergent-free method that allowed them to examine the membrane of an E. coli cell, with lipids still in place.

‘Surprising’ structure
Where earlier models had shown a fluid, almost structureless lipid layer — one often-cited research paper compared it to different weights of olive oil poured together — the VCU-led team was startled to find a distinct hexagonal structure inside the membrane. This has led the researchers to propose that the lipid layer might act as both sensor and energy transducer within a membrane protein transporter.

“The most surprising outcome is the high order with which lipid molecules are arranged, and the idea they might even cooperate in the functional cycle of the export channel,” said Joachim Frank, Ph.D., of Columbia University, a 2017 Nobel laureate in chemistry and coauthor of the paper. “It is counterintuitive since we have learned that lipids are fluid and disordered in the membrane.”

Photo of Youzhou Guo
Guo

The researchers were able to get such a clear view because they used an innovative method to isolate and stabilize the membranes. Employing poly-styrene-maleic-acid to break cell membrane into nanoparticles that were then isolated and captured in a layer of sophisticated polymer, the researchers used the state-of-the-art cryo-electron microscope at New York Structural Biology Center (NYSBC) to get a clear look at the lipid bilayer.

“Being able to pull proteins out of cell membranes without using detergents to break up the lipid bilayers truly is a fantastic advance,” said Wayne Hendrickson, Ph.D., a university professor at Columbia, scientific director of NYSBC and coauthor of the paper.

The technique and its revelations could have significant pharmaceutical value, added VCU’s Guo. He pointed out that about half of medical drugs target the cell membrane, and proposed that improved understanding of their layers of lipids and proteins could lead to new or more-effective therapies.

The authors of the paper, “Structure and Activity of Lipid Bilayer Within a Membrane Protein Transporter,” are Weihua Qiu, Guoyan G. Xu, Yan Zhang and Youzhong Guo, of Virginia Commonwealth University, and Ziao Fu, Robert A. Grassucci, Joachim Frank and Wayne A. Hendrickson of Columbia University.

Pharmacists as part of medical team make patients healthier and reduce costs, study says

A hospital bed.
How can doctors keep patients healthier and out of the hospital? By having pharmacists on the medical team, a new study says.

By Christian Ruiz
Auxiliary Label Staff

Pharmacists working in collaboration with other health-care providers can improve the quality and cost of care for patients, according to a recent study.

A recent article in the American Journal of Health-System Pharmacy makes the case that pharmacists working as part of the primary-care team can be crucial life savers for their patients. In the case of the study, having pharmacists on the team reduced hospitalizations by 23.4 percent and reduced costs by approximately $5 million.

The study — of six hospitals from the Carilion Clinic health system in southwest Virginia in conjunction with 22 patient-centered medical homes associated with Carilion Clinic — was led by VCU School of Pharmacy’s Gary Matzke, Pharm.D.; Leticia Moczygemba, Pharm.D., Ph.D.; Karen Williams, Pharm.D.; Michael Czar, Pharm.D., Ph.D.; and William Lee. The study took place from January 2013 to June 2015. Funding sources for the study included the CMS Center for Medicare and Medicaid Innovation and the Carilion Clinic health system.

A total of 2,480 patients in the study had two or more of these seven chronic health conditions: heart failure, high blood pressure, high cholesterol, diabetes, asthma, chronic obstructive pulmonary disease (COPD) and depression. In addition, the patients were taking at least four medications and had a primary care physician in the Carilion Clinic health system.

The researchers studied the difference between collaborative care, in which pharmacists were members of the primary care team and worked closely with physicians, and “usual care,” in which pharmacists were not part of the primary care team, on the progress of their patients’ chronic health conditions and on their patients’ use of hospital resources.

The collaborative-care pharmacists called patients within 72 hours after their hospital stay to see if those patients had any medication-related problems or issues. Additionally, these pharmacists met the patients face-to-face or by phone to address patient-specific problems or concerns, which encouraged patients to self-manage their medications and health conditions.

Patients in the usual-care group did not interact with pharmacists in these ways.

Patients in the group working more closely with pharmacists showed better improvement in each of their health conditions compared to the usual-care group in terms of their diabetes, high blood pressure and high cholesterol.

In addition, the number of patients who were treated with the collaborative-care group experienced a 23.4 percent decrease in hospitalizations, from 1,675 hospitalizations before treatment by the collaborative-care group to 1,283 hospitalizations after treatment by the collaborative-care group.

The usual-care group, in comparison, experienced an 8.7 percent decrease in hospitalizations, from 355 hospitalizations before treatment and 324 hospitalizations after treatment.

Along with the health improvements, pharmacists in the collaborative-care group helped reduce the cost of hospitalizations overall by $5,156,675 — $2,619 less per patient than standard procedures would have been expected to cost. In comparison, the usual-care group recorded a cost reduction of $475,071, or $241 less per patient than standard procedures would have been expected to cost. This means that pharmacists in the collaborative-care group helped save $4,681,604 more than the usual-care group — or $2,378 more per patient than standard procedures would have been expected to cost — over the course of the study.

This study demonstrates that pharmacists can contribute far more to health care in the community than just serving as “pill counters” – a perceived role that immensely underestimates and undervalues the impact they can have on both the health of their patients and the cost of health care. Additionally, when health care providers work together as a team, our jobs as life savers can be worth so much more to our patients.

Auxiliary Label is a student-created blog examining pharmacy life, education and research at the VCU School of Pharmacy from a student perspective. It is overseen by Greg Weatherford, the school’s director of communications. Contact him here.

Auxiliary Label: Antibiotic stewardship research in a community outpatient setting

An image of a purple C. dificile bacterium.
An image of C. dificile bacterium, based on photomicrographic data. (Centers for Disease Control).

By Victoria Hammond
Auxiliary Label Staff

Antibiotic resistance — when bacteria are untreatable by current antibiotics — is a growing public health concern.

To reduce antibiotic resistance, prescribers use antibiotics only when necessary. In hospital settings, experts called antibiotic stewards monitor trends in resistance, prescribing, costs and adverse effects. Prescribing trends are compared to current treatment guidelines.

Stewards in an antibiotic stewardship have a goal to “enhance patient health outcomes, reducing resistance to antibiotics, and decreasing unnecessary costs,” according to the Society of Healthcare Epidemiology of America.

In 2015, about  269 million antibiotic prescriptions were dispensed in outpatient settings — at least 30 percent of which were unnecessary, according to the U.S. Centers for Disease Control. Unnecessary treatment of antibiotics can increase the risk of side effects or opportunistic infections such as C. difficile.

Settings with high volumes of antibiotics being prescribed would benefit from an antibiotic stewardship program to prevent side effects and opportunistic infection.

To improve patient outcomes in outpatient settings, VCU School of Pharmacy faculty members John Bucheit, Pharm.D.,  Teresa Salgado, M.Pharm., Ph.D., and Amy Pakyz, Pharm.D., Ph.D., have been implementing an antibiotic stewardship program in a free outpatient health clinic in the Richmond area. (They asked that the clinic’s name not be published.)

The faculty members’ first focus targets the prescribing trends of uncomplicated urinary-tract infections, or UTIs. Bucheit, Pakyz and Salgado are developing an antibiogram — a profile of antibiotic susceptibility for a specific practice site — based on prescribing trends from the past two years.

The antibiogram will provide information about which antibiotics are providing beneficial therapy to patients based on the clinic’s antibiotic susceptibility to resistant or nonresistant bacteria. This antibiogram will then be compared with current therapy guidelines to develop clinic specific guidelines for practitioners to use at the clinic. The project was made possible by a grant from the VCU School of Pharmacy’s Center for Pharmacy Practice Innovation.

“We are excited about this project to not only improve patient care at our clinic,” Bucheit said, “but also to provide an example for other outpatient offices interested in improving antibiotic prescribing for uncomplicated UTI.”

After the guideline is developed, Bucheit, Pakyz, Salgado and their team will educate the staff and reevaluate in a year.

The goal of this project is to provide prescriber education and improve patient health outcomes in a setting where high volumes of antibiotics are prescribed.

Auxiliary Label is a student-created blog examining pharmacy life, education and research at the VCU School of Pharmacy from a student perspective. It is overseen by Greg Weatherford, the school’s director of communications. Contact him here.

 

Auxiliary Label: Working to build better opioids

Molecular model of hydrocodone.
A molecular model of hydrocodone. (Credit)

By Christian Ruiz
Auxiliary Label Staff

Opioids are a class of highly addictive pain-relieving drugs derived from the opium in poppy plants. These drugs are at the center of today’s opioid-overdose crisis, in which at least 115 people per day in the United States die after opioid overdoses.

If you have ever had your wisdom teeth removed, you might be familiar with opioid drugs that are not available over the counter but are prescribed by your doctor or dentist: Percocet (oxycodone/acetaminophen), Vicodin (hydrocodone/acetaminophen) or Tylenol No. 3 (codeine with acetaminophen). The widespread availability of these and similar drugs have caused many people to become addicted to opioids. 

At least 33,000 people in this country died in 2015 alone from overdosing on opioids. Overall, misuse of opioid drugs has cost the United States $78.5 billion per year, including the costs of healthcare, lost productivity, addiction treatment and legal system involvement.

However, the major FDA-approved treatments for opioid abuse and addiction — methadone (Dolophine, Methadose), buprenorphine (Belbuca, Buprenex), naloxone (Narcan) and naltrexone (Vivitrol) — are not fully effective in treating opioid abuse and addiction. They have many of the side effects that the opioids themselves have, such as mood disorders.

For several years, Yan Zhang, Ph.D., and his laboratory in VCU School of Pharmacy’s Medicinal Chemistry Department have been working on modifying the chemical structures of drugs used to treat opioid abuse and addiction. In doing so, they hope to reduce the opioids’ addictive potential and their other harmful side effects such as sedation, decreased ability to breathe and constipation.

To do this, they use organic chemistry to synthesize these potential new drugs and then use biochemical techniques to examine how these drugs interact with different, specific proteins in cells.

Proteins: More Than Just for Bodybuilding

To understand how Zhang and his team are working to build better, safer opioids, we need to take a step back and talk about proteins.

Proteins are large molecules that are responsible for many survival functions in the human body. For example, they protect the body against viruses and bacteria, speed up chemical reactions within cells, and provide structure and support for cells. An important function that proteins play, particularly in terms of many drugs and their actions, is to relay biological messages throughout the body.

In essence, the way most drugs work is by binding to these receptor proteins (proteins that “receive” these drugs), which causes these proteins to send biochemical or electrical signals throughout the cells in the body. These signals in turn tell the body to reduce inflammation, relieve a headache or even decrease heart rate, for example.

G protein-coupled receptors are a superfamily of these receptors; opioids bind to a specific group within this superfamily of receptors, called opioid receptors.

The three major types of opioid receptors are named for the Greek letters mu, kappa and delta. For simplicity, these opioid receptors often are abbreviated MOR, KOR and DOR.  

The mu opioid receptor, or MOR, is primarily responsible for relaying signals causing pain relief. The KOR is primarily responsible for relaying signals causing depression and anxiety. The DOR is primarily responsible for relaying signals causing mood-related disorders.

Notably, several studies have shown that the MOR is responsible for relaying other signals, particularly the addictive potential and other harmful side effects of opioids mentioned previously.

These effects on mood are due to opioids’ interactions with the KOR and/or the DOR rather than just the MOR.

Hence, selectively blocking only the MOR should be able to block the signals for addiction, sedation, constipation and the other side effects without relaying the signals for mood disorders caused by interacting with the KOR and/or the DOR. This could mean new treatments for opioid addiction could be developed that avoid these unpleasant side effects. 

With this hypothesis in mind, Zhang’s laboratory group is working on producing new chemical compounds that selectively target the MOR without targeting the KOR and the DOR. After synthesizing these potential, new drugs, the group uses a series of biochemical tests to examine these drugs’ abilities to bind to and to relay biological messages through the MOR, the KOR and the DOR.

Through their hard work, we might one day have a drug to more effectively help those in need during this opioid-overdose crisis.

Auxiliary Label is a student-created blog examining pharmacy life, education and research at the VCU School of Pharmacy from a student perspective. It is overseen by Greg Weatherford, the school’s director of communications. Contact him here.

VCU Pharmacy’s CPPI announces partnership with journal Pharmacy Practice

FOR IMMEDIATE RELEASE
CONTACT: Greg Weatherford
goweatherfor@vcu.edu | (804) 828-6470 (o) (804) 937-4722 (m)

The VCU School of Pharmacy’s Center for Pharmacy Practice Innovation is proud to announce an editorial partnership with Pharmacy Practicea quarterly full-text peer-reviewed online journal.

Pharmacy Practice was founded as an independent journal by a group of prominent pharmacy-practice researchers from around the world about 10 years ago. Pharmacy Practice is free to access, complying with the NIH’s policy on public access, and does not charge for submissions or publication. It is indexed and abstracted on PubMed, PubMed Central, Embase, Scopus, Ebsco EJS and the Directory of Open Access Journals, among others.

As part of the agreement, faculty members of the VCU Center for Pharmacy Practice Innovation will have a designated section to publish non-peer-reviewed articles expressing viewpoints on a wide range of pharmacy-practice topics. VCU School of Pharmacy faculty members Teresa Salgado, M.Pharm., Ph.D. and David Holdford, Ph.D. were named associate editors of Pharmacy Practice; faculty members John Bucheit, Pharm.D.Lauren Pamulapati, Pharm.D., and Julie Patterson, Pharm.D., Ph.D. were named advisory board members.

Notably, the agreement between the journal and the center stipulates that the arrangement remains valid only as long as Pharmacy Practice does not charge authors to publish. No financial support was given or received by the VCU center to execute or maintain the agreement.

“One of our driving motivations for this partnership is to support the open-science philosophy, particularly in an area like pharmacy practice research in which many open access journals charge fees,” explained Salgado, assistant director of the VCU Center for Pharmacy Practice Innovation. “We are honored to join the prestigious group of international colleagues who are part of Pharmacy Practice’s editorial and advisory boards.”

Pharmacy Practice is ranked among the best journals in pharmacy and is among the top journals in the field as determined by the Scopus CiteScore. In fact, Pharmacy Practice is the first open-access journal in this rank.

“We are excited to have an editorial partner as esteemed as the VCU School of Pharmacy’s Center for Pharmacy Practice Innovation,” said Fernando Fernandez-Llimos, Ph.D., editor-in-chief of Pharmacy Practice. “We share the goal of supporting true open-access research of the highest caliber. We look forward to a rewarding partnership.”

For more information contact Greg Weatherford, VCU School of Pharmacy director of communications, at goweatherfor@vcu.edu.

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