(62as) In Vitro Activation of Murine Dendritic Cells by Combinatorially and Conventionally Fabricated Polyanhydride Nanospheres

With the rapid evolution of many diseases, the need for a high throughput approach to the discovery and design of drug/vaccine delivery devices is evident. Combinatorial polymer synthesis and nanosphere fabrication methods provide a rapid means of testing multiple variables (i.e., polymer chemistry) in a single experiment that can lead to accelerated discovery and optimization of adjuvants and/or drug delivery devices. In this work, the combinatorial process was used to study the activation of C3H/HeOuJ dendritic cells (DCs) by varying polyanhydride chemistries. Biodegradable polyanhydrides have been studied for use in single dose vaccines. In particular, polyanhydride nanospheres composed of 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG) and 1,6-bis(p-carboxyphenoxy)hexane (CPH) have not only been shown to be promising candidates for drug delivery, but also as adjuvants. The CPTEG:CPH copolymer system has been shown to possess unique properties such as tailorable release kinetics and the ability to stabilize fragile proteins, making it an ideal candidate for vaccine delivery. The combinatorial evaluation of DC activation by CPTEG:CPH nanospheres was compared to conventional methods for validation of this novel, high throughput process. Specific cell surface markers and cytokine profiles were evaluated in order to compare the performance of nanospheres of varying chemistries and those made by the different processes. It was observed that nanospheres fabricated combinatorially affected the expression of cell surface markers and the production of cytokines in a similar manner to the conventionally fabricated nanospheres; this was demonstrated by an increase in cell surface marker expression and cytokine production as the molar ratio of CPTEG within the copolymer increased, making it less hydrophobic. These insights are valuable in the rational design of single dose vaccines based on nanospheres.