Pharmacy Perspectives - Summer/Fall 2013 - (Page 5)

BY GARTH SUNDEM D PhD Candidate’s Work Highlighted in JOURNAL OF PHARMACEUTICAL SCIENCES A ntimicrobial preservatives are commonly used in multi-dose protein formulations to inhibit the accidental growth of bacteria. However, these preservatives cause protein aggregation, which results in serious immunogenic and toxic effects in patients. Regina Bis (nee Hutchings), together with colleagues in Krishna Mallela’s laboratory, has recently determined the mechanism by which antimicrobial preservatives induce this reaction and that stabilizing the ’hot-spot’ reduces protein aggregation, and in turn has the potential to reduce adverse reactions. Recently published in the Journal of Pharmaceutical Sciences, her work was selected by the editors to be featured on the journal’s website and was cited for “original and most significant scientific findings.” Regina’s work is funded by the PhRMA Foundation and the National Institutes of Health Leadership Training Grant in Pharmaceutical Biotechnology. She has also been awarded a Biotechnology travel grant from the American Association of Pharmaceutical Scientists (AAPS) to present her groundbreaking results at its National Biotechnology Conference in San Diego. Read the full article at onlinelibrary.wiley. com/doi/10.1002/jps.23362/full. MENOPAUSE RESEARCH BEING PURSUED BY FACULTY Faculty member Laura Borgelt, PharmD, in partnership with the American Academy of Family Physicians (AAFP) National Research Network, was NA, siRNA and miRNA can reprogram cancer cells – that is, if these nucleic acids could cross through the cell membrane. A University of Colorado Cancer Center study published by CU Skaggs School of Pharmacy faculty member, Tom Anchordoquy, in the journal Therapeutic Delivery shows that cholesterol “rafts” can shepherd genetic payloads into cancer cells. “There are many promising therapeutic applications for nucleic acids, but because they can’t diffuse across cell membranes on their own, delivery to cancer cells has been a major challenge. Our method is a promising way to get these drugs inside cancer cells where they can do their work,” says Tom Anchordoquy, PhD, investigator at the CU Cancer Center and professor at the Skaggs School of Pharmacy and Pharmaceutical Sciences. The technology works by exploiting a relatively new understanding of what cell membranes look like. “It used to be that we thought about membrane proteins floating around in a disorganized twodimensional soup. Now we know that different functions are clustered into domains we call rafts,” Anchordoquy says. Imagine these rafts like continents of the Earth, each presenting its own plant species. Perhaps a raft with palm trees but not spruce unlocks passage into a cancer cell? Anchordoquy and colleagues aren’t the first to imagine particle-payload delivery systems, but when you engineer and introduce a non-rafted particle into the blood, it quickly becomes coated with all sorts of blood proteins that can cover the membrane proteins (“palm trees”) needed to unlock passage into cancer cells. However, blood proteins don’t bind to rafts and so particles with rafts continue to present the engineered bits rather than being silted over by the body’s proteins. Anchordoquy and colleagues make these rafts by boosting the concentration of cholesterol while forming particles for drug delivery. “See, rafts are made of 30-50 percent cholesterol, about five times the level in the surrounding lipid. We’d shown in earlier experiments that rafts create awarded $499,790 by Pfizer Medical Education to evaluate the management of menopausal symptoms by incorporating electronic tablets into clinical practice for improved data gathering and shared decision making. Approximately half of all women between the ages of 45 and SUMMER/FALL 2013 CHOLESTEROL RAFTS DELIVER DRUGS INSIDE CANCER CELLS more delivery of payload materials into cancer cells, but there was always the outside chance that the benefit was due simply to higher levels of cholesterol and not to the action of the rafts, themselves,” Anchordoquy says. The current study found an elegant fix: with longer tails on lipid molecules, particles will form rafts at lower cholesterol concentrations. The team used long-tailed lipids to form their particles, allowing them to keep cholesterol concentration low while showing the same benefit in delivering genes Rafts are made of 30-50 percent cholesterol, about five times the level in the surrounding lipid. We’d shown in earlier experiments that rafts create more delivery of payload materials into cancer cells, but there was always the outside chance that the benefit was due simply to higher levels of cholesterol and not to the action of the rafts, themselves.” - TOM ANCHORDOQUY into cancer cells. This demonstrates that it is indeed the raft that facilitates delivery. “We’ve used these synthetic rafts to deliver a gene inside these cells that makes the cells fluoresce,” Anchordoquy says. “That way we can see how much payload went in. But because we’re talking particles and not just individual molecules, in the future we can send other cargo like microRNA’s that can reprogram a cell’s gene expression.” Anchordoquy is working with colleagues at the CU Cancer Center to match his delivery system with a potent payload, and welcomes collaboration outside the center as well. 60 years of age experience at least one menopausal symptom or combination of symptoms – everything from hot flashes to weight gain – yet only a third of women talk about treatment options with their provider. And 45 percent of women say information about managing and treating symptoms of menopause is confusing. “Getting through menopause can be challenging, so our goal is to discover if a more patient-focused approach using computer technology and individualized treatment options can help,” says Borgelt. www.ucdenver.edu/pharmacy 5 http://www.onlinelibrary.wiley.com/doi/10.1002/jps.23362/full http://www.onlinelibrary.wiley.com/doi/10.1002/jps.23362/full http://www.ucdenver.edu/pharmacy

Table of Contents for the Digital Edition of Pharmacy Perspectives - Summer/Fall 2013

Pharmacy Perspectives - Summer/Fall 2013
Contents
School News Pharmacist Hunter
Research Collaborations Across Generations
Student News Habitat for Humanity
Graduation - In Depth Coverage
Alumni News Jack of All Trades

Pharmacy Perspectives - Summer/Fall 2013