Poly(Lactide-co-glycolide)-b-Poly(ethylene glycol)-Dibenzocycolctyne

PLA (polylactic acid) is a biodegradable polymer formed by polycondensation of lactic acid monomers, but its degradation products are acidic, poorly hydrophilic, and difficult to control the degradation cycle, which limits its application. Polylactic-co-glycolic acid (PLGA), formed by co-condensation of lactic acid and glycolic acid, has good biocompatibility and biodegradability. Its application in the medical field has been recognized by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), and is currently the most attractive polymer carrier. Polyethylene glycol (PEG) is a water-soluble polyether obtained by the stepwise addition polymerization of water or ethylene glycol and ethylene oxide. It has good biocompatibility and immunogenicity. In recent years, there have been many studies on the introduction of PEG as a hydrophilic component into polymer carriers, mainly through block or grafting methods. The more commonly used one is to combine hydrophobic (PLGA) and hydrophilic (PEG) to form a PEGPLGA block copolymer, which can effectively improve drug water solubility, increase drug stability and reduce immunogenicity.

Figure 1. The gelation mechanism of PLGA-PEG-PLGA (A) and PEG- PLGA-PEG (B) hydrogels.(Gong C, et al. 2013)

As a drug sustained-release and controlled-release carrier, PLGA has greatly promoted the development of pharmaceutical preparations, but its hydrophobicity makes the drug easily cleared by mononuclear macrophages (MPS) in the human body and absorbed in the liver and spleen. PEG has good solubility in water and many organic solvents. After it is connected to a hydrophobic polymer, it can improve its water solubility, so it is often used as the hydrophilic end of block copolymers. The PEG terminal has a primary alcohol hydroxyl group, which can undergo amination, esterification, and etherification reactions to combine with PLGA. Nanoparticles are a type of solid colloidal particles composed of polymer substances with a particle size between 1 and 1000 nm. They can be dispersed in water to form a near-colloidal solution and are highly targeted. PEG-PLGA diblock copolymers and PEG-PLGA-PEG and PLGA-PEG-PLGA triblock copolymers are commonly used PEG-PLGA block copolymers. Typically in copolymers, the polylactic acid portion forms the hydrophobic core of the nanoparticle, which can encapsulate the drug, while the polyethylene glycol portion forms the hydrophilic corona. Further structural examination using nuclear magnetic resonance spectroscopy revealed that in PEG-PLG, the lactide and glycolide chains form a rigid core, with the PEG chains attached to the ends of the core to form a corona structure. The length of the hydrophilic end and hydrophobic end affects the aggregation/assembly behavior of PEG-PLGA, thereby forming nanoparticles with different sizes and structures. PEG－PLGA together with dibenzocycloalkyne (DBCO) to form PLGA-PEG-DBCO is a linear heterobifunctional PEGylated polymer. The polymer has DBCO, which allows it to perform click chemistry without any metal catalyst through copper-free click chemistry reaction of DBCO with the azide to form a stable triazole bond. The DBCO reagent can be used to spontaneously label azide-modified biomolecules without the need for toxic copper catalysts. PEGylation without the involvement of toxic catalysts increases solubility and stability and reduces the immunogenicity of peptides and proteins. It also inhibits non-specific binding of charged molecules to modified surfaces.

The main advantages of PEG-PLGA carrier are: 1. Improve drug bioavailability; although researchers strive to find new drugs to treat Parkinson's disease, the bioavailability of most drugs is reduced due to the effect of the blood-brain barrier (BBB). Candidates fail in preclinical and clinical trials. The surface of PLGA can be modified with enzymes or other polymers to increase its efficiency in reaching its target site. Compared with the traditional carrier PLGA, PEG-modified PLGA changes the release rate of the drug, increases the drug's action time in the body, and improves the stability and targeting of nanoparticles. In addition, PEG can also increase the anti-stickiness of nanoparticles. In mucosal drug delivery systems, drugs often reduce their bioavailability due to adhesion to mucus. PEG-modified PLGA can increase its anti-stickiness and reduce the adsorption of PLGA by mucus or the possibility of clearance, quickly passing through the mucus barrier to reach mucosal epithelial cells, promoting the body's absorption of drugs. 2. Achieve sustained release of drugs; experimental studies have shown that PEG-PLGA can produce sustained release of drugs. Rapamycin (RAPA) has pharmacological effects in treating atherosclerosis, but its water solubility is poor. RAPA-PEG-PLGA-NPs were prepared using PEG-PLGA as a carrier. In vitro release experiments showed that after preparing RAPA into nanoparticles, The sustained release lasts for 5 days, and the cumulative release amount reaches more than 70%.

Alternate Names:
PLGA-PEG copolymer
PLGA-PEG block copolymer
Poly(lactic-co-glycolic acid)-polyethylene glycol
PLGA-PEG conjugate
PLGA-PEG hybrid
PLGA-PEG polymer
PEGylated PLGA

References:
1. Gong C, et al. Thermosensitive polymeric hydrogels as drug delivery systems. Curr Med Chem. 2013, 20(1):79-94.

Q & A

Q: What are the storage conditions for the product?

A: The product should be stored under nitrogen or argon at low temperature (-20℃). This product should be kept away from light.

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