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Review
. 2020 Feb 14:8:89.
doi: 10.3389/fbioe.2020.00089. eCollection 2020.

Nanosized Delivery Systems for Therapeutic Proteins: Clinically Validated Technologies and Advanced Development Strategies

Filippo Moncalvo  1 , Maria Isabel Martinez Espinoza  1 , Francesco Cellesi  1
Affiliations
Review

Nanosized Delivery Systems for Therapeutic Proteins: Clinically Validated Technologies and Advanced Development Strategies

Filippo Moncalvo et al. Front Bioeng Biotechnol. .

Abstract

The impact of protein therapeutics in healthcare is steadily increasing, due to advancements in the field of biotechnology and a deeper understanding of several pathologies. However, their safety and efficacy are often limited by instability, short half-life and immunogenicity. Nanodelivery systems are currently being investigated for overcoming these limitations and include covalent attachment of biocompatible polymers (PEG and other synthetic or naturally derived macromolecules) as well as protein nanoencapsulation in colloidal systems (liposomes and other lipid or polymeric nanocarriers). Such strategies have the potential to develop next-generation protein therapeutics. Herein, we review recent research progresses on these nanodelivery approaches, as well as future directions and challenges.

Keywords: PEGylation; liposomes; nanocarriers; polymer conjugates; protein delivery; therapeutic proteins.

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Figures

FIGURE 1
FIGURE 1
Different conjugation strategies used for protein PEGylation.
FIGURE 2
FIGURE 2
The ‘grafting to’ and ‘grafting from’ conjugation strategies. In a ‘grafting to’ method, end-functionalised polymers are firstly synthesized and then attached to the protein via a conjugation reaction. In a ‘grafting from’ method, a low molecular weight initiator is firstly attached to the protein and then the polymerization is initiated directly from the protein.
FIGURE 3
FIGURE 3
Liposome designed for therapeutic protein delivery. Protein is generally entrapped within the liposome core (of tunable diameter d), and its encapsulation may also involve hydrophilic/hydrophobic interactions with the lipid bilayer. Liposomes can be PEGylated to prolong circulation in vivo, and may be conjugated with active ligands to provide active targeting.
FIGURE 4
FIGURE 4
Main steps involved with the preparation of protein-loaded liposomes, including typical tasks and drawbacks (MLV: Multilamellar Vesicles, LUV: Large unilamellar vesicles, SUV: small unilamellar vesicles).
FIGURE 5
FIGURE 5
Different types of nanosized systems for protein delivery, including lipid-based, and polymer-based nanocarriers.
See this image and copyright information in PMC

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