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

Abstract

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.

Sustained release of VEGF from PLGA nanoparticles embedded thermo-sensitive hydrogel in full-thickness porcine bladder acellular matrix

“…This ultimately leads to a sustained diffusion of protein from the particles. Another quality attribute of NPs is the entrapment efficiency which should be properly optimized to avoid the loss of drug during processing [ 22 ]. It is of the highest importance especially in case of drugs such as VEGF, with their cost being very high.…”

Development of Polysorbate 80/Phospholipid mixed micellar formation for docetaxel and assessment of its in vivo distribution in animal models

“…As well known, the single component micelles is composed of amphipathic micromolecules, so the particle size of the single component micelles with drug filled in is usually far smaller than most of the drug loaded carriers [ 17 ]. In our study, the mean diameter of DTX-loaded Polysorbate 80 micelles was only 7.89 ± 1.97 nm.…”

Optimized Preparation of Celastrol-Loaded Polymeric Nanomicelles Using Rotatable Central Composite Design and Response Surface Methodology

“…Carboxyl-terminated Pluronic P123 nanomicelles filled with celasrtol was prepared using the thin-film hydration method as described previously. [31][32][33] Briefly, celastrol and carboxyl-terminated Pluronic P123 were dissolved into dichloromethane. After complete dissolution, the organic solvent was evaporated under reduced pressure at 25 C to form a thin, dry film layer on the wall of flask.…”