Supercritical fluid technology: A game-changer for biomacromolecular nanomedicine preparation and biomedical application

Biomacromolecules are attractive in biomedical applications as therapeutic agents and potential drug carriers due to their natural active components, good biocompatibility, and high targeting. However, their large relative molecular weight, complex structure, susceptibility to degradation, and poor stability limit their usefulness. Nanotechnology can address these issues by improving the therapeutic value, bioavailability, permeability, and absorption of biomacromolecules while regulating their retention time in the body. Especially, compelling evidence has been reported that supercritical fluid (SCF) technology has emerged as an alternative that maintains the integrity of biomacromolecules and reduces environmental contamination. In this review, we highlight a set of unique nanosizing strategies based on SCF technology for biomacromolecular nanomedicine, and extensively discuss their characteristics and mechanisms. In particular, the protein-based, nucleic acid-based, and polysaccharide-based nanomedicine preparations via SCF technology and their biomedical applications are summarized, and the potential for industrial production of biomacromolecular drugs is also considered. We further provide perspectives on the opportunities and challenges in this excellent field of biomacromolecular drugs nanotechnology.