Thiol-PEG-Amine is a specialized chemical which is becoming increasingly popular in drug delivery for its special nature and versatility. It consists of a polyethylene glycol (PEG) structure, a thiol group (-SH) at one side and an amine group (-NH2) at the other side to make a functionalized polymer with biomedical uses. PEG is an effective drug delivery material because it is hydrophilic, solubilizing and less immunogenic. The thiol atom offers reactive sites for recombination with other molecules and the amine atom gives it more functionalization and interactions with biological systems. All these attributes combined make Thiol-PEG-Amine an exciting candidate for drug solubility, stability and targeting efficiency in pharmaceutical products. Enhanced pharmacokinetics of encapsulated drugs is one of Thiol-PEG-Amine's most important drug delivery properties. Thiol-PEG-Amine PEG ingredient has "stealth" activity to protect the drug from immune system degradation and elimination before the end of the period of time. This longer circulatory window in the blood makes them efficient to accumulate at the point of action (as in targeted delivery systems). Further, the thiol group also allows stable conjugates with any biomolecule, be it peptide, protein or small-molecule drug, to be covalently bound to the polymer. This covalent attachment gives the drug stability and may even avert premature absorption or loss of therapeutic effect. In addition, the amine unit can bind to several different receptors in cells to promote cellular uptake and enhance the overall therapeutic index of the drug. Thiol-PEG-Amine's flexibility also extends to the application of targeted and controlled drug delivery systems. Through a change in the structure of the PEG polymer or by clinging on to the thiol group specific targeting ligands, you can target drug delivery to tissue, cell or even intracellular space. Such targeted targeting is especially important in the treatment of cancers, where chemotherapeutic agents are hoped to enter tumor cells with as little damage to healthy tissues as possible. Also, because PEG can contain degradable linkers between the PEG and the drug molecules, controlled release systems can be engineered. These mechanisms can dispense the drug in response to specific environmental conditions, such as pH or the activity of certain enzymes, so that they can precisely time and dosage the drug. This controlled release process improves the therapeutic potential of the drug with less side effects.
Figure 1. Structure of thiol-PEG-modified AuNPs (PEGylated AuNPs). (Wang W, et al.; 2013)
Thiol-PEG-Amine has several distinct features that distinguish it as a drug delivery technology. The best thing about it is that it forms active covalent bonds with other biomolecules. This is because the thiol group at one end of the polymer is very reactive and can easily disulfide bond to cysteine residues on proteins or peptides. This property will be of great benefit in the design of targeted delivery systems in which a therapeutic protein or peptide can be fused to the polymer backbone for a more stable and effective carrier for biologics. These disulfide bindings also make sure that the drug will release under certain reducing conditions, such as inside the target cells (particularly useful for intracellular delivery of drugs). This sort of release is ideal for selectively transporting proteins, nucleic acids or other massive biomolecules that would otherwise be uncooperative or poorly absorbed by cells. There is a second important application of Thiol-PEG-Amine in nanomedicine as it is a promising candidate for drug-packed nanoparticles preparation due to its properties. The thiol group can bind to nanoparticles small molecules, proteins or other therapeutic agents; the PEG is used to stabilize the particles and make them bio-available. These nanoparticles can be engineered to attack cells or tissues by adding targeting moieties to the PEG chain. Furthermore, the amine group can be added for additional modification and functionalization with customizable functions for gene delivery, immune suppression or anti-inflammatory drugs. Utilized together with nanocarriers such as liposomes, SLNs or micelles, Thiol-PEG-Amine can revolutionize drug delivery systems through the accurate and efficient delivery of hydrophilic and hydrophobic drugs. Thiol-PEG-Amine application in stimulation-sensitive drug delivery systems is a further research hotbed. If you add pH-sensitive linkers or enzyme-cleavable bonds to the polymer structure, Thiol-PEG-Amine can be made to release its drug payload upon a stimulus. In the case of cancer therapy, for instance, the polymer could release its active ingredient only when it comes into contact with an acidic environment in a tumour or with particular proteases. This sort of drug release is likely to transform drug therapeutics in ways that are dramatically less toxic to healthy tissue. Additionally, the thiol group can be used to synthesize hydrogels that respond to temperature, ionic strength or pH change, which could be used to engineer injectable drug delivery devices that gel at the site of injection and release the drug over time. This kind of mastery of the drug release profile is vital in most therapeutic areas — especially for chronic diseases or long-term treatments.
Thiol-PEG-Amine is a promising candidate in the delivery of drugs, but there are still several issues to overcome before it can be clinically implemented. The primary issue is off-target effects from nonspecific attachment of the polymer to a site that was not intended. Despite the reduction of immunogenicity and improved circulation time achieved by PEGylation, there is still a chance that the drug will latch on to unwanted proteins or tissues and cause undesirable effects. For this reason, scientists are developing more advanced methods of binding to particular cells or tissues with ligands or antibodies attached to the polymer. This strategy can ensure the drug gets to its target of action and therefore becomes safer and more effective. The other problem is the chance that the polymer can build up in the body, gradually. PEGylation may lessen clearance, but in the long term, PEG accumulation will be added as prolonged exposure to PEG may cause immune response or other complications. To counter this, scientists are looking into biodegradable PEG derivatives that can be safely metabolised and cleared from the body following administration of a drug. As for the future, there are many possibilities for Thiol-PEG-Amine in the area of drug delivery and research continues on overcoming these hurdles and expanding the potential applications. The fact that it's chemically novel, functionalised, and can be used to deliver many different drugs makes it a promising area for development. Until we learn more about how it interacts with biology, Thiol-PEG-Amine will probably be more central to personalized and precision medicine. As nanotechnology, biotechnology and materials science progress, Thiol-PEG-Amine might be the foundation of next-generation drug delivery systems with more targeted, controlled and efficacious therapies for a variety of diseases.
Alternate Names:
PEG-SH-Amine
Amine-PEG-SH
Amine-terminated thiol-PEG
PEGylated thiol amine
Thiol-terminated PEG amine
PEG thiol amine
Thiol-modified PEG amine
(Polyethylene glycol)-thiol amine
References:
1. Wang W, et al.; Role of thiol-containing polyethylene glycol (thiol-PEG) in the modification process of gold nanoparticles (AuNPs): stabilizer or coagulant? J Colloid Interface Sci. 2013, 404:223-9.
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