The Development of PEG Modified Small Molecule Drugs

Among all of the PEG (polyethylene glycol) modified small molecules, the anti-tumor drugs, focusing on paclitaxel and hetotaxine, are the most frequently studied. Although these small molecules are generally with high toxicity, the large dosage is required to achieve the effective treatment. Pegylation has the ability to settle the defects in the physicochemical properties and pharmacokinetics of small molecule drugs. The effects of PEG on small molecule drugs are enhancing solubility, reducing toxicity, increasing half-life and delaying release.

Due to the good water solubility of PEG derivatives, the drugs formed by conjugating PEG with small molecules can be quickly dissolved in water by searching for the terminal groups that can bind to specific small molecule drugs, so the drugs are made into injections to be absorbed by the human body.

In addition, the relative molecular weight of small molecule drugs is generally not so large, and it is easily filtered out of the human body by the kidney. The drug effect is not obvious if the small molecule drug concentration in human body is low, while it will have strong side effects on the human body if the concentration is too high. Therefore, only when within a certain concentration range, the small molecules can work stably. As the relative molecular weight of small molecule drugs modified by PEG increases, it avoids them being quickly filtered out of the body, and an effective drug concentration in the human body can be maintained with a single injection. As a result, the lesion site can maintain an effective drug concentration continuously during the administration to increase the half-life of the drug effect and reduce the frequency of medication for patients.

Generally, small molecule drugs contain a large amount of effective compounds, but there are certain defects in their physicochemical properties and pharmacokinetics. Theoretically, these small molecule drugs can be optimized and upgraded by PEG.

There are only a small quantity of PEG-modified small molecule drugs approved for market in the world. With the increasingly sophisticated PEG technology, they will be extended to more small molecule drugs. It is expected that the future market scale of the PEG-modified small molecule drugs are capable of exceeding that of PEG-modified protein peptide drugs.

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