Programming and switching the pharmacokinetics of nanoscale delivery vehicles in vivo

M.-P. Chien, N.C. Gianneschi
University of California, San Diego, US

Keywords: pharmacokinetics, drug delivery

Summary:

It has been shown that the morphology of nanomaterials greatly impacts the pharmacokinetic profile of the material, with larger micronscale fibril-like objects having longer circulation times while smaller nanomaterials show a greater rate of internalization into cells. We have developed two nanoparticle systems (DNA- and peptide-polymer micellar systems) that combine these properties and allow us to program pharmacokinetics and ADMET properties in vivo by virtue of morphology switches via endogenous or exogenous stimuli. We show, the circulation half-life of DNA containing polymeric micelles in blood in vivo can be modulated via a programmed morphology switch (long circulating fiber structures switched to short circulating spherical structures) triggered by an exogenously injected DNA stimulus. The second system utilizes peptide polymer amphiphilic nanoparticles where the outer shell is composed of a peptide that is responsive to specific cancer-associated MMP enzymes. We have shown that these materials undergo a morphology switch from small sphere to large aggregate upon reaction with MMPs in tumor tissue resulting in the accumulation of the materials in the diseased tissue. These two systems have broad implications for the design of nanoscale-materials in drug delivery and diagnostics applications where tunable pharmacokinetics can play a role in enhanced targeting and clearance.