Poly(lactic-co-glycolic acid), or PLGA, is a polymer that is a copolymer, meaning it is composed of two different monomer units: lactic acid and glycolic acid. This material is both biocompatible and biodegradable, which signifies it can be safely used within the human body and will break down over time into harmless substances. Because of these characteristics, PLGA has been approved by regulatory bodies like the U.S. Food and Drug Administration (FDA) for use in a variety of therapeutic devices.
Core Properties and Synthesis
PLGA is valued for its biocompatibility, meaning it does not provoke a significant immune or inflammatory reaction when introduced into the body. A defining feature of PLGA is its biodegradability; it is designed to break down and be absorbed by the body, eliminating the need for surgical removal of devices made from it. The mechanical strength and flexibility of PLGA are not fixed, but can be adjusted, making it a versatile material for a range of medical needs.
The synthesis of PLGA is most efficiently achieved through a process called ring-opening copolymerization. This chemical reaction starts with the cyclic dimer forms of lactic acid (called lactide) and glycolic acid (called glycolide). These ring-shaped molecules are opened up and linked together to form the long polymer chains of PLGA. This method allows for the creation of high-molecular-weight polymers, which are necessary for medical devices that require durability.
Biomedical Applications
PLGA’s properties make it suitable for a wide array of biomedical applications, particularly in the field of controlled drug delivery. The polymer can be formed into microparticles or nanoparticles that encapsulate a drug. This allows for the slow and sustained release of medication over weeks or even months from a single injection. This approach improves patient adherence to treatment regimens for conditions like hormonal disorders or certain psychiatric illnesses. The polymer protects the encapsulated drug from premature degradation in the body.
In the domain of tissue engineering, PLGA is used as a temporary scaffold to support the regeneration of tissues such as bone and cartilage. These scaffolds are porous structures that can be seeded with a patient’s own cells in a lab. Once implanted, the scaffold provides the necessary physical support for the new tissue to grow and organize. As the new tissue matures and fills in the damaged area, the PLGA scaffold gradually degrades and is naturally eliminated by the body.
The material is also used to manufacture medical devices and implants that are designed to be resorbed by the body. This includes surgical sutures that dissolve on their own, as well as screws and plates used to fix bone fractures.
The Degradation Process
The breakdown of PLGA within the body occurs through a chemical process known as hydrolysis. This process is initiated when water molecules present in bodily fluids attack and break the ester bonds that link the lactic and glycolic acid units in the polymer chain. This is a non-enzymatic process, meaning it does not rely on specific enzymes in the body to proceed. The degradation occurs in phases, starting with random chain scission that reduces the polymer’s molecular weight.
As hydrolysis continues, the PLGA polymer is broken down into its original, harmless building blocks: lactic acid and glycolic acid. These two substances are natural products that are already present in the human body. The body is well-equipped to handle them without causing toxic effects.
Once released, both lactic acid and glycolic acid are processed through normal metabolic pathways. Lactic acid, for instance, is a common byproduct of muscle metabolism and is readily used in the Krebs cycle to produce energy. Ultimately, these components are converted into carbon dioxide and water, which are then easily eliminated from the body.
Controlling PLGA Behavior
Scientists and engineers can precisely adjust the behavior of PLGA to meet the specific requirements of a medical application. The primary method for controlling its properties is by altering the ratio of lactic acid (LA) to glycolic acid (GA) in the polymer chain. This LA:GA ratio directly influences how quickly the polymer degrades.
Lactic acid is more hydrophobic (water-repelling) than glycolic acid due to its methyl group. Consequently, a PLGA formulation with a higher percentage of lactic acid will absorb water more slowly and, as a result, degrade over a longer period. Conversely, increasing the glycolic acid content makes the polymer more hydrophilic (water-attracting), leading to faster water penetration and more rapid degradation. A 50:50 ratio of the two monomers typically results in the fastest degradation rate.
The molecular weight of the polymer chains also plays a part in its behavior. A higher molecular weight, corresponding to longer polymer chains, produces a stronger material that takes more time to break down. For example, a drug delivery system requiring a quick release of medication might use a low-molecular-weight PLGA with a high glycolic acid content. In contrast, a bone screw that needs to provide structural support for several months would be made from a high-molecular-weight PLGA rich in lactic acid.