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

Liang-Kai Chu,S Ranil Wickramasinghe,Andrew L Zydney,Xianghong Qian

doi:10.3390/membranes12030299

Liang-Kai Chu, S Ranil Wickramasinghe + Show 2 more

Open Access

https://doi.org/10.3390/membranes12030299

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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.

Highlights

Recent advances in gene therapy have created renewed interest in the development of biological and synthetic nanoparticle systems for the delivery of RNA and DNA therapeutics
One challenge in the development of nanoparticle-based therapeutics is the development of effective purification schemes
Our results provide important insights into the factors controlling nanoparticle filtration, providing a framework for future studies of membrane systems for the purification of nanoparticle-based biotherapeutics

Summary

Introduction

Recent advances in gene therapy have created renewed interest in the development of biological and synthetic nanoparticle systems for the delivery of RNA and DNA therapeutics. Liposomes and lipid nanoparticles protect nucleic acids from degradation and improve pharmacokinetics [1], forming the basis for mRNA vaccines against COVID-19. Recombinant viral vectors, including both lentivirus [2] and adeno-associated virus (AAV) [3], provide high transfection levels to effectively deliver mRNA and DNA to specific target organs [4]. Nanoparticles can be used to treat solid tumors, e.g., through the generation of hydroxyl radicals that inhibit tumor growth [5]. One challenge in the development of nanoparticle-based therapeutics is the development of effective purification schemes. This includes ensuring sterility of the final product. There is a need to separate empty from full (DNA- and RNAcontaining) capsids [8–10], which have similar physical characteristics

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