An Optimization Zwitterionic LNP for Drug Delivery
Polyethylene glycol (PEG) is a polymer material widely used for the covalent modification of proteins and peptides. PEGylation is a drug technology that covalently binds PEG to a drug to improve its pharmacokinetic, pharmacodynamic, and immunological properties, enhancing its therapeutic effect. PEG has become one of the most commonly used polymer materials because of its non-toxic, non-immunogenic, non-antigenic, and good water solubility. PEG can change the physicochemical properties of the drug, which leads to the improvement of the retention time of the drug in the body and the prolongation of the half-life. In addition, PEG will also affect the binding affinity of the drug to the cell receptor and improve tumor targeting. The impact of PEG on drugs is more than that. After PEG modifies the drug, it can reduce the number of administrations, improve the efficacy, improve the tolerance, and reduce the severity and the incidence of adverse events. At the same time, PEG can also increase the solubility and stability of proteins, which is also beneficial to the production and storage of drugs. Therefore, PEG is often used as a drug delivery and modification technology, which can be directly coupled with drugs or attached to the drug surface and encapsulated in nanomaterials.
Fig.1 Main advantages of PEGylated protein
PEGylated drugs generally include PEG, coupled drugs and linkers (Linker), and other parts. PEGylation is the optimization of drug solubility, immunogenicity, and biological function through various conjugated chemistries and linkers (shown in Fig.2). However, PEG also shows some defects in drug treatment. Researchers have found that long-term administration will lead to the accumulation of PEG in tissues, resulting in adverse reactions and tissue toxicity; the metabolism of PEG can also lead to the formation of acid metabolites which may cause side effects. In addition, it has been reported in the literature that long-term administration can also cause the production of PEG antibodies, reducing the therapeutic effect. Therefore, evaluating the safety and pharmacokinetic characteristics of improving PEG is essential. Recently, researchers have developed a non-immunogenic zwitterionic polymer as a material for drug therapy. The polymer has no toxicity, and long-term administration does not cause polymer accumulation and tissue lesions. The zwitterionic polymers exhibited significantly improved pharmacokinetic and immunological properties compared to conventional PEG. Therefore, this polymer has excellent potential for drug delivery.
Fig.2 PEGylated drugs
The Advantages of this platform include:
- Non-immunogenic and non-toxic
- Improved pharmacokinetic and immunological
- Extend drug half-life
Potential Applications
- Drug delivery system
- Modification of proteins
- Development of polymer materials
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References
- Veronese FM, Pasut G. PEGylation, successful approach to drug delivery. Drug Discov Today. 2005 Nov 1;10(21):1451-8. DOI: 10.1016/S1359-6446(05)03575-0.
- Prajna Mishra, Bismita Nayak, R.K. Dey, PEGylation in anti-cancer therapy: An overview, Asian Journal of Pharmaceutical Sciences, 2016, 337-348, https://doi.org/10.1016/j.ajps.2015.08.011.