Purpose: The ERK1/2 signaling pathway is upregulated following heart failure events, and PD98059 has been identified as drug to reduce ERK1/2 signaling. Administering PD98059 shortly after a heart failure event is effective at reducing long-term effects, however, delivering the drug at the necessary concentration for a sustained period of time is difficult.
Methods: We have developed nanoparticles, microparticles, and pellets from poly(lactic-co-glycolic acid) (PLGA) loaded with PD98059 with the objective of obtaining rapid, sustained release profiles. Loading and release were assessed using high performance liquid chromatography (HPLC). Optimization of formulations that provide early, but long-term sustained release was informed by experimental results.
Results: PLGA particles, both with and without drug, were developed on the nanoscale (200 – 400 nm) and the microscale (20-30 um). The lower limit of detection for drug release measured with HPLC was in the 50-100 ng/mL range. Release from particles began as early as a couple of days, whereas pellet formulations had later initial release and longer sustained release.
Conclusion: In developing various formulations, we were able to assess advantages and disadvantages of each as it pertains to clinical translation. The current treatment option requires that the patient remain in a hospital setting to receive a continuous infusion of soluble drug. However, the formulation presented here offers the potential for out-patient treatment therefore improving the quality of life.
Youssef Naguib– University of Iowa
Khanidtha Chitphet– PhD student, University of Iowa
Supreeda Tambunlertchai– Graduate Student, University of Iowa, Iowa City, Iowa
Aliasger Salem– Professor, College of Pharmacy, University of Iowa, Iowa City, Iowa