Dextran-based Nanocarriers as Efficient Media Delivery Vehicles to Cell Production Bioreactors

Decreasing the volume of media required to maintain cell viability not only reduces contamination of bioreactors from the upstream process, but may contribute to cost-containment measures in the biopharmaceutical industry. Based on our recent finding that dextran-containing nanocarriers increased CHO cell density up to 20 fold compared to its cellulose-containing microcarrier counterpart (manuscript submitted), we then investigated the possibility of reducing media volume to maintain cell viability, by utilizing the same dextran-based nanocarrier prepared from a self assembling nanoemulsion (SANE) method, and an adherent Chinese hamster ovary (CHO) cell culture line to evaluate media volume requirements. At the same 60 mL volume of media, cell viability after day 3 was 6 fold greater in CHO cells exposed to dextran-containing nanocarriers compared to cellulose-based microcarriers. When CHO cells were exposed to 60 mL of media containing dextran-based nanocarriers compared to 100 mL of media for cellulose-microcarriers, at day 6, cell density was up to 7 fold greater. Similarly, cell lysate protein concentrations at day 6 was nearly 3 fold greater for CHO cells exposed to dextran-containing nanocarriers compared to the cellulose-based microcarriers. Furthermore, nanocarriers had 59% greater glucose concentration, used as a measure of the polymer dextran and cellulose content levels in the nanocarriers and microcarriers, respectively. In conclusion, nanocarriers with increased numbers of dextran molecules, developed in these studies may be useful to further optimize media volume requirements for maximum culture growth.