Inventory of polyethylene glycol applications in the medical field

Polyethylene Glycol (PEG)  is a pH-neutral, non-toxic, highly water-soluble hydrophilic polymer with a linear or branched chain structure. PEG is the polymer with the lowest protein and cell absorption level among all known polymers to date. Due to its non-toxicity and good biocompatibility, PEG has been approved by the FDA as a polymer for in vivo injection.

Application in pharmacy

Polyethylene glycol has been widely used in the field of pharmacy. Due to its different degree of polymerization, the molecular weight of polyethylene glycol is usually between 200-35000, and its chemical formula is HO(CH2CH2O)nH. In pharmacy, polyethylene glycol can be mainly used as a drug solvent, drug additive or excipient, plasticizer and pore-forming agent, drug carrier, modified material and penetration enhancer, etc.

Polyethylene Glycol (PEG) as a drug solvent

1. Injection

PEG200-600 aqueous solutions of different concentrations are good solvents that can improve the solubility of poorly soluble drugs and have a stabilizing effect on water-unstable drugs, so they can be used as injection solvents.

2. Eye drops

Using PEG400 as a solvent, indomethacin eye drops can be made, and the PEG400 prescription is better than the Span80 prescription. In addition, PEG can be used as a thickener in eye drops to increase viscosity and prolong the drug's residence time in the eye, thereby increasing the efficacy and reducing irritation.

Polyethylene glycol as an additive or excipient

1. Co-solvent

Polyethylene glycol can form a co-solvent with water in liquid additives to improve the solubility of poorly soluble drugs.

2. Binders and lubricants

PEG4000 and PEG6000 are commonly used water-soluble binders and lubricants in tablets. The granules made with polyethylene glycol as a binder have good formability and the tablets do not harden, which is suitable for granulation of water-soluble or water-insoluble materials.

3. Stabilizers

For example, polyethylene glycol can be added to liquid dosage forms of protein drugs to change the properties of the protein to increase its stability. High concentrations of PEG are often used as cryoprotectants and precipitants/crystallizers for proteins, and they can interact with the hydrophobic chains of proteins. Studies have shown that PEGs of different molecular weights have different effects. For example, PEG300 at a concentration of 0.5% or 2% can inhibit the aggregation of recombinant human keratinocyte growth factor; PEG200, 400, 600 and 1000 can stabilize BSA and lysozyme.

Polyethylene glycol as a drug carrier

1. Matrix

Appropriate PEG mixtures (such as equal amounts of PEG300 and PEG500) have a certain paste consistency, which makes them have good solubility in water and good drug compatibility, and can be used as a water-soluble matrix for ointments. Its advantages are: PEG will not cause skin allergies, and it is stable and does not deteriorate. Soft PEG applied on the skin surface does not affect human sweating. Since PEG is not electrolyzed, its pH value can be adjusted to any required value to meet human needs.

2. Solid dispersion materials

Because PEG has good water solubility and can be dissolved in a variety of organic solvents, it can disperse certain drugs in a molecular state, thereby preventing drug aggregation. Therefore, in solid dispersion materials, PEG can be used as a water-soluble carrier material to increase the dissolution rate of drugs. PEG can also be used as a carrier material for sustained-release solid dispersions. For example, by using the melting method, the drug is dissolved in the molten PEG, and the drug solution is loaded into a hard capsule. The drug solution solidifies at room temperature and the drug is slowly released according to the dissolution mechanism, so it has a sustained-release effect. In addition, different PEG contents will also form different types of solid dispersions.

3. Polymeric nano-micelles

Polymer micelles are mostly studied as homopolymer and copolymer micelles. For example, polyethylene glycol can be used to form the hydrophilic region of amphiphilic block copolymers, and the hydrophobic materials in the hydrophobic region together with PEG form various diblock or triblock amphiphilic polymers, which can form various micelles and expand the drug loading range.

For example, after copolymerization of PCL and polyethylene glycol, the hydrophilicity of PCL particles can be increased to form amphiphilic copolymers, which changes the polymer sphering properties. The amphiphilic copolymer is loaded with drugs to form nano-micelles. The hydrophobic groups of the copolymer improve the system's loading performance for oil-soluble drugs such as paclitaxel, while the hydrophilic groups improve the water solubility of paclitaxel.

4. Modified materials

When polyethylene glycol is used as a modified material, it can be used to modify drugs to change the properties of the drug's action, and it can also be used to modify drug carriers to improve the performance of the original carriers. Structural modification using PEG can improve the following properties of drugs:

(1) Increase stability and reduce enzyme degradation;

(2) Improve pharmacokinetic properties, such as prolonging plasma half-life, reducing maximum blood drug concentration, and reducing blood drug concentration fluctuations;

(3) Reduce immunogenicity and antigenicity;

(4) Reduce toxicity and improve in vivo activity;

(5) Improve drug distribution in the body and enhance targeting;

(6) Reduce the frequency of medication and improve patient compliance.

1. Modified protein drugs

Polyethylene glycol can be chemically modified by covalently linking to proteins. Protein PEG modification can change the biochemical properties of proteins, including molecular size, hydrophobicity and charge, thereby increasing the water solubility and stability of proteins. In addition, it can also reduce the immunogenicity of proteins, improve drug efficacy and safety, etc. PEG modification of proteins can be performed on amino, thiol or carboxyl groups of proteins.

2. Modified drug carriers

Preparation and in vitro drug release study of polyethylene glycol-modified polyamide-amine (PAMAM)-methotrexate (MTX) molecular complexes. Functionalized PEG is connected to the amino group on the surface of PAMAM through an amide bond. The hemolytic toxicity of PEGylated PAMAM is investigated, and PAMAM-PEG/MXT complexes are prepared. The maximum complex amount is determined, and the in vitro drug release behavior of the complexes in different buffer solutions and plasma and the stability under different storage conditions are investigated. Finally, according to the experimental results, it was found that compared with PAMAM, the hemolytic toxicity of PAMAM-PEG was significantly reduced, and it had a certain sustained release effect, which is expected to become a new drug delivery carrier material.

3. Modification of small molecule drugs

In addition to being used to modify proteins, carriers and other macromolecular substances, many organic small molecule drugs are also gradually using PEG modification technology. For example, some small molecule drugs are modified with polyethylene glycol. Dichlorothionyl is used as a coupling agent. After the small molecule drug is chloroformylated, it is bonded to polyethylene glycol with a degradable lipid bond. The results show that this method improves the yield of the target modified product, and the water solubility of PEG-modified nicotinic acid is improved.