PEGylation of drugs is the coupling of activated polyethylene glycol (PEG) to proteins, polypeptides, small molecule organic drugs and liposomes through chemical methods. As the excipient of traditional pharmaceutical preparations, PEG has been widely used in the field of anti-tumor drug delivery system due to its unique physical and biological characteristics.

The PEGylation research of anticancer drugs has a history of more than 40 years. These drugs include proteins, polypeptides, small molecule drugs, etc., and many of them have been approved for marketing or have entered clinical research. The PEGylated anti-tumor drug technology can prolong the half-life of the drug,Fmoc-OSu enhance the stability of the drug, reduce the immunogenicity and antigenicity, improve the pharmacokinetic and pharmacodynamic properties by changing the molecular structure of the drug, and increase the blood concentration at the action site. At the same time, compared with unmodified drugs, pegylated drugs show better tolerance, thus increasing the clinical application range and efficacy of injected drugs, which has become a hotspot in the field of anti-tumor drug research

The properties of PEG and the significance of PEG modified antitumor drugs

Peg is a safe, non-toxic and inactive polymer. It is a long-chain macromolecular polymer based on the repeated ethylene glycol oxide. It has two terminal hydroxyl groups. Its molecular structure can be linear (relative molecular weight: Fmoc-Pen(Acm)-OH 5000-30000) or branched (relative molecular weight: 40000-60000). The molecular weight varies according to the number of och2ch2. PEG modification refers to that one or several PEG molecules are adsorbed on biological macromolecules such as proteins and polypeptides or interact with small molecules through chemical bonds or chemical forces to improve their pharmacokinetics and pharmaceutical properties and achieve better clinical effects.

Due to the low reactivity of PEG terminal hydroxyl group, one terminal hydroxyl group of PEG is often activated to methoxy group in order to couple with protein at a high rate under mild conditions. The peg used for drug modification is actually monomethoxypolyethylene glycol (MPEG). The molecular formula of linear MPEG is CH3. (0.ch2-ch2). Oh. Therefore, PEGylation modification of drugs is a process of coupling activated peg to drugs by chemical methods.

It is generally believed that most anti-tumor drugs will undergo the following changes after PEG modification:

 ① the immunogenicity and antigenicity are decreased; 

② Improve the kinetic properties of the drug (the half-life is prolonged, the clearance rate is decreased, and the blood drug peak concentration is decreased); 

③ Increased solubility; 

④ The thermal stability is improved; 

⑤ Reduced toxicity; 

⑥ Resistant to protease hydrolysis; 

⑦ The frequency of medication was reduced; 

⑧ The bioavailability was improved; 

⑨ PEG modified liposomes have stronger passive targeting effect on tumor.