Retention and Fouling during Nanoparticle Filtration: Implications for Membrane Purification of Biotherapeutics

Abstract

One major challenge in the development of nanoparticle-based therapeutics, including viral vectors for the delivery of gene therapies, is the development of cost-effective purification technologies. The objective of this study was to examine fouling and retention behaviors during the filtration of model nanoparticles through membranes of different pore sizes and the effect of solution conditions. Data were obtained with 30 nm fluorescently labeled polystyrene latex nanoparticles using both cellulosic and polyethersulfone membranes at a constant filtrate flux, and both pressure and nanoparticle transmission were evaluated as a function of cumulative filtrate volume. The addition of NaCl caused a delay in nanoparticle transmission and an increase in fouling. Nanoparticle transmission was also a function of particle hydrophobicity. These results provide important insights into the factors controlling transmission and fouling during nanoparticle filtration as well as a framework for the development of membrane processes for the purification of nanoparticle-based therapeutics.

Role of Microfiltration Membrane Morphology on Nanoparticle Purification to Enhance Downstream Purification of Viral Vectors

“…Their study established a clear connection between higher buffer concentrations and the hydrodynamic diameter of BSA, which, in turn, may be the driving force behind the more pronounced fouling behavior evident in our declining flux results. Moreover, this buffer-related impact on filtration mirrors the findings of Chu et al, who, while investigating a similar system involving viral vector-like nanoparticles, observed an elevation in transmembrane pressure with increasing buffer concentration . This observation suggests heightened fouling behavior with increasing buffer concentrations.…”

“…Moreover, this buffer-related impact on filtration mirrors the findings of Chu et al, who, while investigating a similar system involving viral vector-like nanoparticles, observed an elevation in transmembrane pressure with increasing buffer concentration. 28 This observation suggests heightened fouling behavior with increasing buffer concentrations. Our research underscores the critical role of buffer composition in membrane-based viral vector purification, given its substantial impact on filtration performance.…”

“…29,30 In earlier work, done by Chu et al, the retention of 30 nm polystyrene nanoparticle suspensions was investigated as a model for AAV3. 28 Moreover, a recent study investigating single pass tangential flow filtration of 100 nm nanoparticles indicated they are a good model for lentivirus. 23 Overall, the use of nanoparticles provides a controlled and reproducible model, facilitating insights into the dynamics of the purification process, specifically when employing size-based exclusion principles.…”

“…Synthetic nanoparticles have been increasingly utilized as model particles in process optimization studies. − This approach enables researchers to investigate and optimize various parameters, such as buffer and surfactant concentrations, for enhanced viral vector-like nanoparticle throughput . Several investigators have considered the use of model particles as contaminants in water treatment applications. , In earlier work, done by Chu et al, the retention of 30 nm polystyrene nanoparticle suspensions was investigated as a model for AAV3 . Moreover, a recent study investigating single pass tangential flow filtration of 100 nm nanoparticles indicated they are a good model for lentivirus .…”

Single-Pass Tangential Flow Filtration (SPTFF) of Nanoparticles: Achieving Sustainable Operation with Dilute Colloidal Suspensions for Gene Therapy Applications

“…Several previous studies have used nanoparticles as viral surrogates in membrane filtration. This includes the removal of virus-sized particles from water [29][30][31], as well as the use of polystyrene latex nanoparticles as models for rhabdovirus [32], liveattenuated virus [33], and adeno-associated viral vectors [34]. In addition to their use as a model virus, nanoparticles have also been explored as vehicles for targeted drug delivery [35], with ultrafiltration used to concentrate the product and standardize formulation properties [36][37][38][39].…”