Polycaprolactone (PCL), also known as polyε-caprolactone, is an organic polymer with the chemical formula (C6H10O2)n. It is synthesized by ε-caprolactone monomer under the catalysis of a metal anion complex catalyst. High-molecular organic polymers formed by cyclopolymerization can obtain different molecular weights by controlling polymerization conditions. Its appearance is an opaque white solid powder, non-toxic, with certain rigidity and strength. It shows typical resin characteristics, is insoluble in water, and is easily soluble in various polar organic solvents such as toluene, tetrahydrofuran, ethyl acetate and dichloromethane. PCL has good biocompatibility, good compatibility with organic polymers, and good biodegradability. It can be used as a cell growth support material and is compatible with a variety of conventional plastics. It can be completely degraded within 6-12 month in the natural environment. In addition, because PCL has five non-polar methylene groups and one polar ester group on its structural repeating units, it has good flexibility and processability, and the products have shape memory. It is widely used in the production and processing fields of drug carriers, degradable plastics, nanofiber spinning, etc.
Figure 1. PEG-PCL-based nanomedicines.(Grossen P, et al. 2017)
PCL is used in several medical fields due to its unique properties, including tissue regeneration and drug delivery. PCL can be used as a biological scaffold material. Tissue engineering technology focuses on the extracellular matrix that supports cell growth, proliferation, differentiation, and function. In the human body, the extracellular matrix (ECM) is similar to a scaffold, consisting of 3D nanofibrous structures made of collagen and other biopolymers. Therefore, if made from nanofibers, 3D scaffolds can provide biomimetic structures similar to ECM. The nanoscale features of nanofibrous scaffolds have a high surface area to volume ratio, which enhances cell adhesion and cell migration and helps deliver nutrients to cells more efficiently. Scaffolds used in tissue engineering are often made from natural and synthetic polymeric materials. PCL is excellently biocompatible, non-toxic, has excellent mechanical properties, and can be hydrolyzed or degraded by enzymes in the body, making it an ideal polymer for scaffolds. PCL is a linear hydrophobic synthetic polymer with high mechanical strength and good biocompatibility, and the PCL nanofiber scaffold structurally mimics the ECM in living tissue. However, because PCL is hydrophobic and has no cell activity, it is necessary to combine gelatin with PCL to make a composite scaffold that can effectively improve cell adhesion and proliferation properties, and has stability and flexibility.
In addition to the above-mentioned applications in the field of tissue engineering, PCL is also very attractive in the field of new drug delivery systems. The synthetic biodegradable material PCL has good biocompatibility, blood compatibility, and drug permeability, and has been approved by the FDA for use in humans. However, PCL is highly hydrophobic, which limits its application in the medical field. If nano-preparations are directly made from PCL, they will be quickly blocked by the liver and spleen organs and tissues after intravenous injection, and then be recognized and engulfed by the monocyte-macrophage system, resulting in a shortened half-life in the blood. In order to meet the application in the medical field, hydrophilic segments are usually introduced into the molecular chain, such as polyethylene glycol (PEG) and PCL are copolymerized to obtain amphiphilic PEG-PCL diblock copolymers, which can be used to prepare Preparations such as nanoparticles, micelles, nanogels, polymersomes, and dendrimers. In the nanodrug-carrying system prepared with PEG-PCL as a carrier, the hydrophobic PCL is located inside the drug-carrying system, and the hydrophilic block PEG is covered on the surface. Due to the protection of the PEG hydrophilic layer, the drug-loaded system can avoid recognition and phagocytosis by the monocyte-macrophage system, thus greatly increasing the half-life of the drug in the blood and extending the drug circulation time. In addition, PEG has a hydroxyl group that can be modified, and different functional groups are connected to the hydroxyl group, such as amino group, carboxyl group, maleimide group, etc. Through different functional groups, the surface of the PEG-PCL drug delivery system can be connected to different ligands, such as peptides, antibodies, carbohydrates, nucleic acid aptamers and small molecules, etc., for specific targeted delivery of drugs, targeted drug delivery systems It can significantly improve the accumulation of drugs in specific areas, enhance bioavailability and therapeutic effects, and reduce side effects. PEG-PCL as a drug carrier is one of the important directions for achieving targeted drug delivery.
Alternate Names:
Poly(ε-caprolactone)
Poly(ε-caprolactone) (PCL)
Poly(ε-CL)
ε-Polycaprolactone
Poly(1,4-dioxane-2-one)
PCL polyester
References:
1. Grossen P, et al. PEG-PCL-based nanomedicines: A biodegradable drug delivery system and its application. J Control Release. 2017, 260:46-60.
Dual-drug delivery of Ag-chitosan nanoparticles and phenytoin via core-shell PVA/PCL electrospun nanofibers
Carbohydr Polym.
Authors: Mohamady Hussein MA, Guler E, Rayaman E, Cam ME, Sahin A, Grinholc M, Sezgin Mansuroglu D, Sahin YM, Gunduz O, Muhammed M, El-Sherbiny IM, Megahed M.
Abstract
Dual-drug delivery systems were constructed through coaxial techniques, which were convenient for the model drugs used the present work. This study aimed to fabricate core-shell electrospun nanofibrous membranes displaying simultaneous cell proliferation and antibacterial activity. For that purpose, phenytoin (Ph), a well-known proliferative agent, was loaded into a polycaprolactone (PCL) shell membrane, and as-prepared silver-chitosan nanoparticles (Ag-CS NPs), as biocidal agents, were embedded in a polyvinyl alcohol (PVA) core layer. The morphology, chemical composition, mechanical and thermal properties of the nanofibrous membranes were characterized by FESEM/STEM, FTIR and DSC. The coaxial PVA-Ag CS NPs/PCL-Ph nanofibers (NFs) showed more controlled Ph release than PVA/PCL-Ph NFs. There was notable improvement in the morphology, thermal, mechanical, antibacterial properties and cytobiocompatibility of the fibers upon incorporation of Ph and Ag-CS NPs. The proposed core-shell PVA/PCL NFs represent promising scaffolds for tissue regeneration and wound healing by the effective dual delivery of phenytoin and Ag-CS NPs.
PEG-PCL-based nanomedicines: A biodegradable drug delivery system and its application
J Control Release
Authors: Grossen P, Witzigmann D, Sieber S, Huwyler J.
Abstract
The lack of efficient therapeutic options for many severe disorders including cancer spurs demand for improved drug delivery technologies. Nanoscale drug delivery systems based on poly(ethylene glycol)-poly(ε-caprolactone) copolymers (PEG-PCL) represent a strategy to implement therapies with enhanced drug accumulation at the site of action and decreased off-target effects. In this review, we discuss state-of-the-art nanomedicines based on PEG-PCL that have been investigated in a preclinical setting. We summarize the various synthesis routes and different preparation methods used for the production of PEG-PCL nanoparticles. Additionally, we review physico-chemical properties including biodegradability, biocompatibility, and drug loading. Finally, we highlight recent therapeutic applications investigated in vitro and in vivo using advanced systems such as triggered release, multi-component therapies, theranostics, or gene delivery systems.
Polymeric modification and its implication in drug delivery: poly-ε-caprolactone (PCL) as a model polymer
Mol Pharm.
Authors: Dash TK, Konkimalla VB.
Abstract
Biodegradable polymers provided the opportunity to explore beyond conventional drug delivery and turned out to be the focus of current drug delivery. In spite of availability of diverse class of polymers, several of these polymers lack important physicochemical and biological properties, limiting their widespread application in pharmaceutical drug delivery. However, most polymers in the form of blends, copolymers and functionally modified polymers have exhibited their applicability to overcome specific limitations and to produce novel and/or functionalized formulations for drug delivery as well as tissue engineering. This review aims to provide the need of polymeric modification, approaches adopted to modify and their scope. Special emphasis has been given to synthetic polyester PCL, as it is widely demonstrated in its modified form to overcome its problem of hydrophobicity and much slower degradation over the past decade. Past studies show a significantly higher utility of modified form of PCL in comparison to its native form. From the statistical analysis of these modifications and the formulations prepared, we present a basic understanding of the impact of selective modifications on the formulation design. In conclusion, we remark that a thorough understanding of the polymer and its modification has a huge potential to be the future trend for drug delivery and tissue engineering applications.
Datasheet
