PCL Background As an aliphatic polyester material, poly ε-caprolactone (PCL) has excellent biodegradability and biocompatibility. Since PCL was first synthesized in the 1980s, it is still widely used in tissue engineering and drug delivery systems, such as bone self-repair, skin, smooth muscle cells, surgical sutures, heart valves, etc. From the perspective of crystallization properties, PCL has semi-crystalline characteristics, with a crystallinity of approximately 45%. Compared with other types of aliphatic polyester polymer materials, PCL has some unique characteristics due to its molecular structure and composition, such as extremely low glass transition temperature (Tg) (approximately -65°C) , relatively low melting point (about 65°C). Therefore, at room temperature, the appearance of PCL is rubbery and has a certain toughness. Compared with other aliphatic polyester materials, PCL has better drug permeability due to its lower glass transition temperature. However, unlike other types of aliphatic polyester materials that begin to decompose at 250°C, PCL will only decompose under higher temperature conditions (decomposition temperature is 350°C), so PCL has good thermal stability.
Figure 1. 5 Properties of polycaprolactone.(Mallesh Kurakula, et al.; 2021)
In the early 1970s, PCL nanoparticle carriers were first proposed and prepared to achieve controlled and sustained release of drugs. At the same time, the drug permeability and biodegradability of PCL as a drug carrier were systematically studied. With the deepening of research, various properties of PCL nanoparticle carriers have been gradually explored and improved. For example, when the relative molecular weight of the drug loaded on PCL nanoparticles is small, it shows excellent drug permeability. When the relative molecular weight of the drug is the same, the permeability of PCL nanoparticle carriers to the drug is significantly better than that of nanoparticle carriers prepared from other aliphatic polyester materials. When the nanoparticles are loaded with progesterone drugs, the permeability of the PCL nanoparticle carrier to the drug is 105 times that of the PLA nanoparticle carrier. It can be seen that PCL nanoparticle carriers have excellent performance in drug permeability and biodegradability. Therefore, PCL is widely used in the research of controlled-release and sustained-release carriers. In addition, PCL is also used to prepare biodegradable long-acting anti-fertility preparations, which can be prepared in different shapes to meet various needs.
In Vivo Degradation of PCL
Researchers have found that PCL can be degraded due to hydrolysis reactions in the presence of water molecules in the physiological environment of animals, and can also be degraded due to the action of certain lipases in the physiological environment. 6-Hydroxycaproic acid (C6H12O3) is its preliminary degradation product and can be completely metabolized and excreted from the body by the citric acid cycle. Other molecular segments produced during the initial degradation process can be engulfed by phagocytes in physiological environments due to their lower relative molecular mass, and complete the degradation process within the cell. The process of PCL being metabolized and circulated in the body until it is completely degraded and excreted is basically the same as the in vivo degradation process of PGA and PLA. However, the longer methylene chain segment on the PCL molecular chain hinders the hydrolysis reaction of PCL to a certain extent, so the hydrolysis process of PCL is extremely long. It takes at least 2 years for PCL to be degraded in the physiological environment of the body through metabolic circulation and finally excreted from the body. Moreover, the time for complete hydrolysis and excretion from the body is closely related to the relative molecular weight of PCL. When the molecular weight of PCL in the body is about 100,000, the time for complete absorption and excretion from the body takes about 3 years.
PCL Block Copolymer
Block polymer refers to a linear polymer copolymer in which molecular segments with different molecular structures and molecular components are alternately grafted into the same main chain through chemical methods and other means. By copolymerizing different single polymers into block polymers, its own properties can be effectively improved. The resulting block copolymer can have the advantages of its individual components, while the defects can be improved. Block copolymers can freely adjust their molecular weight and the proportions of each component by controlling the original input. Experimental conditions can be changed to obtain block polymers with narrow molecular weight distributions. The molecular structure and components can change the selected raw materials. The molecular structure of the block copolymer is obtained. Therefore, the study of block copolymers is of great significance.
How to design and obtain block copolymers that meet people's needs is a hot research topic today. Block copolymers can have the advantages of each of its components at the same time, and have broader application prospects. Block copolymers can be divided into: diblock copolymers, triblock copolymers, etc. according to the number of chain segments; whether there is regularity in the alternating polymerization of different molecular segments can be divided into: regular block copolymers, random block polymers.
Because of its excellent performance, PCL has been widely used in fields such as tissue engineering and environmental engineering. However, compared with other synthetic degradable polymer materials, it is still slightly insufficient in some aspects. For example, the molecular structure of PCL results in low hydrophilicity and slow degradation rate, which does not meet the requirements for rapid absorption and metabolism. Therefore, PCL needs to be modified to a certain extent so that it can meet the expected needs. Among them, the most reported modification method is to graft hydrophilic groups on the PCL segment, so that under certain humidity conditions, the degradation rate can be accelerated due to the influence of the hydrophilic groups. For example, the copolymerization of PCL and natural polymers (cellulose, lignin, chitosan, etc.), the copolymerization of PCL and other cyclic esters (LLA, DTC, etc.), or the copolymerization of PCL and polyethers (PEG).
PCL-PEG
PCL-PEG is an amphiphilic block copolymer copolymerized by PCL and PEG. Because PCL has poor hydrophilicity, PEG with stronger hydrophilicity is usually used to improve the hydrophilic properties of PCL. There are many ways to prepare PEG. It can be prepared by polymerizing polyoxyethylene with water or ethylene glycol. It can also use ethylene oxide as a monomer and use a catalyst to polymerize it into PEG. PEG not only has good biocompatibility and outstanding hydrophilic properties, but also has the advantages of low immunogenicity and no toxic side effects. Therefore, PEG has been approved by the US FDA for use in pharmaceutical, medical, cosmetics and food industries. After PEG is copolymerized with other polymers, the resulting block copolymer can not only retain the original physical and chemical properties of PEG itself, but also improve or enhance the performance of the copolymer. When PEG is used as raw material to prepare nanoparticles, the PEG chain segments on the surface of the nanoparticles can not only improve the hydrophilic properties and anti-protein adhesion properties of the nanoparticles, but also effectively prevent the nanoparticles from being recognized by the body's phagocytic system.
References
- Bhadran A, et al.; Recent Advances in Polycaprolactones for Anticancer Drug Delivery. Pharmaceutics. 2023, 15(7):1977.
- Sousa-Batista AJ, et al.; Polycaprolactone Antimony Nanoparticles as Drug Delivery System for Leishmaniasis. Am J Ther. 2019, 26(1): e12-e17.
- Mallesh Kurakula, et al.; Fabrication and characterization of polycaprolactone-based green materials for drug delivery. Applications of Advanced Green Materials. 2021, pp.395-423.
