Fabrication and Characterization of Drug Delivery Methods for Resiquimod (2016)

Undergraduates: Kaylyn Pogson, Matthew Gallovic Dr. Kristy Ainslie

Faculty Advisor: Kristy Ainslie
Department: Biology

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There are currently three FDA-approved adjuvants for vaccines, and there is a need to develop more potent adjuvants to formulate more effective vaccines. We used the 7/8 TLR agonist resiquimod (R-848), as it causes a potent cytokine response. Using polymeric and lipid based drug delivery systems (DDS), we sought to determine the most promising by which R-848 may be delivered to the body to develop its use as an adjuvant. R-848 was encapsulated at 3% loading by weight within the following DDS: poly (lactic-co-glycolic acid) microparticles (MPs) by emulsion and solvent evaporation (EM), acetalated dextran (Ace-DEX) MPs by EM, Ace-DEX MPs by electrohydrodynamic spraying, and thin-film hydration liposomes. Each DDS was evaluated for endotoxin content and determined to be within the FDA¿¿¿s endotoxin guidelines for water for injection. The DDS were found to have predictable morphology, encapsulation efficiency, and drug release in pH 5.0 (phagosomal pH) and pH 7.4 conditions. The cellular viability, proliferation, and lack of apoptosis established high cytocompatibilities for the various DDS. Nitrous oxide and pro-inflammatory cytokine production by RAW 264.7 macrophages demonstrated the successful delivery of R-848 to proper intracellular receptors. The Ace-DEX MPs formulated by EM were particularly effective in maintaining cytocompatibility while releasing the drug in a pH-sensitive manner. Overall, we illustrate the potential for delivering R-848 adjuvant using Ace-DEX DDS.