Characterization of Cytokine-Encapsulated Controlled-Release Microsphere Adjuvants.

Controlled-release, injectable polymer microspheres provide a clinically feasible alternative to gene-modificationfor the local, sustained delivery of cytokines to tumors for cancer immunotherapy. Long-term releasekinetics, bioactivity profiles, and stability of interleukin-2 (IL-2), interleukin-12 (IL-12), and granulocyte-macrophage colony-stimulating factor (GM-CSF)-encapsulated microspheres prepared by phaseinversion nanoencapsulation (PIN) were evaluated. While all formulations released physiologically relevantquantities of cytokine for up to 30 days, the individual release kinetics were different. Recovery ofspecific activity after encapsulation was 40%, 60%, and 90%—that of pre-encapsulation levels for IL-2,GM-CSF and IL-12, respectively. Upon storage, the IL-12 microspheres rapidly lost activity, whereasIL-2 and GM-CSF microspheres remained stable for at least 9 weeks. These studies demonstrate that biochemicalproperties of microsphere formulations vary depending on the cytokine, and rigorous characterizationof formulations is a prerequisite to in vivo testing. [ABSTRACT FROM AUTHOR]