Monthly Publication Highlights Insights into Liposomal Drug Delivery
Mar 17, 2014
A research article that advances our understanding of how drug therapy for cancer treatment may be optimized is the UK College of Pharmacy Research Publication Highlight for March 2014.
The article was published in The Journal of Controlled Release and is entitled, “The role of pH and ring-opening hydrolysis kinetics on liposomal release of topotecan.”
Kyle Fugit, a graduate student in the laboratory of Dr. Brad Anderson, the H.B. Kostenbauder Professor in Pharmaceutical Sciences at the College, served as first author on the publication with his mentor.
Liposomal drug delivery systems have been extensively investigated and have shown great potential for cancer therapy; however, they have yet to realize their full clinical potential. A greater mechanistic understanding is needed to optimize and design liposomal drug delivery systems which are capable of controllable release of therapeutic agent tailored to tumor type and patient. The authors addressed this gap in our knowledge by developing and experimentally validating a mathematical model for the liposomal release kinetics of the anti-cancer agent topotecan, a topoisomerase I inhibitor that undergoes reversible, pH-sensitive ring-opening hydrolysis. The studies determined the pH-sensitivity of topotecan release from unilamellar liposomes and developed a mechanism-based mathematical model to account for observed transport rates, including topotecan speciation via ionization, membrane-binding equilibria, drug species' permeability coefficients, and the kinetics and pH-dependence of topotecan lactone ring-opening interconversion.
“The parametric approach in this publication serves as a paradigm for the future design and optimization of liposomal formulations of drugs, particularly those with low solubility, and increases our understanding of factors governing liposomal-based product performance,” said Linda Dwoskin, Associate Dean for Research. “The overall goal is to design delivery systems with optimal therapeutic efficacy and minimal toxicity to patients, thereby facilitating "bench-to-bedside" drug development.”