Formulation of a Nanoparticle Drug Delivery System for Camptothecin Prodrugs

Abstract

Drug delivery systems targeting cancer have come into focus in recent years as a potential way of directing known therapeutics to specific sites in order to minimize harm to healthy cells and maximize the chemo-toxic potency against cancer cells. Nanoparticle drug delivery via composite gels has been shown by Pinkerton et al. to be a viable way to deliver drugs directly to lung tissue. This study analyzes PLA-b-PEG nanoparticles with camptothecin prodrugs in the core as a potential means of drug delivery to reduce small cell lung cancer tumors. Both 1-decanol and α-tocopherol were tested as lipid anchors for the camptothecin prodrug. The α-tocopherol prodrug created the highest quality nanoparticles based on size and narrow polydispersity, encapsulated most efficiently, and was most compatible with co-core lipids. While the prodrug performed its expected funtions and followed a predictable, numerically derived reaction rate during bulk hydrolysis in Milli-Q® water, there was limited prodrug hydrolysis when encapsulated in nanoparticles. Initial experiments indicate that using a formulation with a high prodrug mass to co-core POPC lipid ratio of 7:1 (producing a peak size of 70 nm) is the most promising for future exploration into nanoparticle-based drug delivery for the campothecin prodrug based on the potential for the zwitterionic lipid to induce water partitioning into the nanoparticle.