Methoxy Poly(ethylene glycol)-b-Poly(caprolactone)

In the case of advised drug delivery, the need for biocompatible and effective carriers to bring medicines to points of action have led to a variety of nanomaterials. One of the best candidates for such applications is the block copolymer mPEG-PCL, which fuses the best of polyethylene glycol (PEG) and polycaprolactone (PCL). mPEG-PCL is a block copolymer that is a hydrophilic PEG and hydrophobic PCL, each of which has its own special properties for better encapsulating and delivering drugs. This bicomponent structure allows mPEG-PCL to create micelles, nanoparticles and other nanostructures to optimize the pharmacokinetics, bioavailability and therapeutic properties of numerous drugs. mPEG-PCL's popularity in the delivery of drugs has to do with its multifunctionality, such as increasing drug solubility, blood time in circulation, and minimizing unwanted cross-linking with healthy tissues. Biocompatibility and biodegradability of components are among the many strengths of mPEG-PCL. The best known PEG is how it makes nanoparticles "stealthy" so the immune response doesn't catch up and the circulation time in the blood increases. This property is essential for long-term drug release and the therapeutic efficacy. Then there's polycaprolactone (PCL), a biodegradable polyester that not only structurally reinforces the composition, but it also slowly degrades in vivo without producing toxicity. By combining the two, mPEG-PCL-based systems could bypass some of the major shortcomings of older carrier drugs such as early clearance, low target targeting and rapid degradation. mPEG-PCL's properties of hydrophobic drug delivery in a stable state and controlled release render it an attractive option for highly toxic or poorly soluble drugs such as anticancer agents, immunotherapies and vaccines. This adaptability is in mPEG-PCL's capability to be used for both passive and active drug delivery. Passive targeting: The mPEG coating permits the nanoparticles to slip past the immune system and collect in tumor tissue or inflammation due to the EPR property. This can happen in solid tumours too, as the tumour's dysfunctional vasculature means nanoparticles tend to settle faster than those in healthy tissue. Active targeting is where functional groups or ligands can be added to the mPEG-PCL nanoparticles and targeted receptors overexpressed on the surface of the target cell can then bind. This makes it possible to give the drug much more precisely, with fewer side effects and greater therapeutic success. And even the surface modification of mPEG-PCL can be adjusted to improve cellular uptake, giving more precise control over delivery. This unique set of targeting methods makes mPEG-PCL an all-purpose toolkit for next-generation drug delivery systems.

Figure 1. Schematic synthesis route of mPEG-PCL copolymer. (Danafar H, et al.; 2014)

It is this ability of mPEG-PCL to self-assemble into micelles, nanoparticles and vesicles – among other nanostructures – that makes it stand out from the rest of the drug delivery class, according to PEG:PCL ratio and other formulation variables. The hydrophilic PEG chains will normally be used to make the surface shell of the polymer and the hydrophobic PCL molecules are the inner part that can contain a drug or other bioactive material. This self-assembler also depends heavily on temperature, concentration, and solvent, and so the shape, stability and release profile of the delivery system can be tailored. The particle size of the mPEG-PCL nanoparticles is also can be controlled within a narrow range that helps in drug delivery and target selection. In addition, the drug release characteristics of mPEG-PCL are also variable to support both burst and sustained release profiles, depending on the chemical profile of the drug and the clinical situation of the therapeutic intervention. Degradation rate of mPEG-PCL is another unique feature of mPEG-PCL for drug delivery. PCL hydrolyses in physiologic conditions, where it is reduced to non-toxic compounds easily excreted from the body. Degradation speed can be manipulated depending on the PCL's molecular weight, polymer chain length and formulation. This is how scientists can tweak the degradation rate to the desired release profile of the drug, by changing these parameters. For instance, for cancer drug delivery, the agent is being delivered it is generally preferable to allow for slow degradation in order to allow for sustained drug delivery. Such control over degradation process adds accuracy to the delivery mechanism so that the therapeutic agent is given at the right speed and concentration over time. A key feature of mPEG-PCL is the load of all sorts of hydrophobic drugs, that are hard to inject with traditional systems. Hydrophobic drugs like paclitaxel, curcumin and other chemotherapy drugs are not much solubilised in water that they are no longer bioavailable and effective. mPEG-PCL nanoparticles can then insulate these drugs within their hydrophobic centre, preventing them from being damaged early and making them more easily soluble in living systems. Such encapsulation not only enhances bioavailability of the drug, but also avoids degrade due to exposure to light, oxygen and enzymatic reactions. Furthermore, the drug release kinetics of mPEG-PCL nanoparticles can be tuned by changing the polymer composition and therefore rate of release can be adjusted to suit specific therapeutic demands.

Because mPEG-PCL can carry hydrophilic and hydrophobic drugs, is biocompatible and biodegradable, it is the perfect carrier for various therapeutic applications. For cancer treatment, for instance, mPEG-PCL nanoparticles have been studied as delivery system for chemotherapeutics directly to tumour cells to boost therapeutic index without off-target effects.Traditional chemotherapy has severe side effects since the drugs also go to healthy tissue but, with mPEG-PCL carriers, they can be engineered to release drugs only into the tumor microenvironment and have higher efficacy and lower toxicity. In addition, because you can change the surface of mPEG-PCL nanoparticles to include targeting ligands like antibodies or peptides, it is possible to create very targeted delivery systems that can target cancer cells or any other diseased cell preferentially. This targeted method could transform cancers, autoimmune conditions and even some viral infections, where targeted delivery of therapy is the key to best effect. Besides cancer treatment, mPEG-PCL has also been considered for other uses such as in the administration of vaccines, gene therapies and anti-inflammatory drugs. mPEG-PCL nanoparticles in vaccines have been deployed to capture antigens and adjuvants, which gives the formulation more stability and a more potent immune response. The nanoparticles could also be made to secrete the antigen gradually, which would lengthen and intensify the immune response. So, too, has mPEG-PCL demonstrated activity as a gene therapy device that delivers plasmids, siRNAs or CRISPR/Cas9 to cells. Since mPEG-PCL can shield these delicate genetic elements from degradation and ensure that they're efficiently absorbed by cells, it is a useful agent for gene therapies. mPEG-PCL nanoparticles will be able to bind anti-inflammatory medications and take them to inflammation points, alleviating systemic side effects and increasing therapy effectiveness. The other promising use for mPEG-PCL is in the eye where it has been tested for the delivery of drugs to the eye. The eye has its own drug-delivery challenges: the corneal epithelium, for instance, and the blood-retinal barrier. Such barriers could potentially be broken by mPEG-PCL nanoparticles and treated to improve vision disorders like age-related macular degeneration, diabetic retinopathy and glaucoma. This control of ocular tissue release could have transformative effects on patient outcomes by offering targeted and long-lasting delivery without the need for frequent dosing.

Alternate Names:
mPEG-PCL Block Copolymer
Methoxy Poly(ethylene glycol)-Poly(caprolactone) Copolymer
mPEG-b-PCL
Methoxy-PEG-b-PCL
PEG-b-PCL
PEG–Caprolactone Block Copolymer
Methoxy-Polyethylene Glycol-Polycaprolactone (mPEG–PCL) System
Poly(ethylene glycol)-b-Poly(caprolactone) with Methoxy End Group

References:
1. Danafar H, et al.; Biodegradable m-PEG/PCL Core-Shell Micelles: Preparation and Characterization as a Sustained Release Formulation for Curcumin. Adv Pharm Bull. 2014, 4(Suppl 2):501-10.

Q & A

Ask a Question

Customer Reviews