Protein/peptide drugs have the characteristics of high biological activity, strong specificity and solubility, and low toxicity, and play a key role in the treatment of cancer, metabolic disorders and autoimmune diseases.
Difficulties in Protein/Peptide Delivery
Compared with small molecule drugs, protein/peptide drugs have high specificity and superior biocompatibility. In addition, protein therapy can bypass the requirement to make permanent or random changes to a cell's genome and is a safer treatment than gene therapy. However, protein/polypeptide drugs cannot pass through the intestinal mucosal barrier because they are easily destroyed by gastric acid or degraded by digestive enzymes, so even if they reach the gastrointestinal tract, their bioavailability is still very low.
Major barriers to oral delivery of peptide/protein-based drugs. (Cao SJ, et al., 2019)
Protein/Peptide Delivery System
The development of new protein/peptide drug delivery systems is an effective way to improve drug bioavailability. Compared with the classical route, the new delivery system should be stable, can protect protein/peptide drugs from enzymatic degradation and inactivation, and be able to achieve targeted delivery and release the drug under appropriate kinetics and conditions.
Although the oral route is a disadvantage for protein/peptide drugs, most nanoparticle delivery systems can help them overcome the barriers of susceptibility to enzymatic degradation and poor membrane permeability. Protein and peptide drug-loading nanoparticles have four pathways (transmembrane transport, receptor-mediated transport, carrier-mediated transport, and M-cell transport) across the gastrointestinal membrane.
Schematic representation of the transport mechanisms. (Cao SJ, et al., 2019)
- Polymer Carrier
Polymer carriers include polymeric micelles, polymeric bodies, nanogels, and dendrimers, among others. Among them, polymeric micelles can encapsulate oppositely charged proteins through electrostatic interactions. Dendrimers are used for drug delivery due to their controllable structures and surface groups.
Dendrimer-based polymer and its features in intracellular protein delivery. (Liu X, et al., 2019)
- DNA Nanostructures
The unique programmability of DNA enables the design of uniform nanostructures with well-defined shapes and hybridizations for protein/peptide drug delivery. DNA nanostructures have excellent biocompatibility due to the degradability of DNA by DNase in tissues and can easily enter cells through endocytosis.
Virus-like particles (VLPs) are considered as efficient delivery systems that can deliver not only nucleic acids but also proteins/polypeptides. The delivery of the protein/polypeptide is achieved by linking to the VLP by genetic fusion or chemical conjugation. Specifically, there are four main methods for applying peptides.
VLP has a variety of methods to deliver proteins/peptides, but only when it is a nanomaterial can the delivery be achieved by electrostatic interactions or passive encapsulation of protein/peptide drugs.
How We can Help
As a global leader in the production and application of VLPs from VLPlantTM platform, CD BioSciences leverages its expertise to help our customers deliver protein/peptide. We are good at tailoring our services to the needs of our clients. Please contact us if you are interested.
Our capabilities include but are not limited to:
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- Cao SJ.; et al., Nanoparticles: Oral Delivery for Protein and Peptide Drugs. AAPS PharmSciTech. 2019, 20:190-200.
- Liu X.; et al., Recent Advances in Anti-cancer Protein/Peptide Delivery. Bioconjug Chem. 2019, 30:305-324.