Poly(lactic-co-glycolic acid), commonly known as PLGA, is a synthetic polymer widely used in biomedical science. This material is favored because it is both biocompatible and biodegradable, meaning it can safely interact with the body and then dissolve naturally over time. Having received approval from the U.S. Food and Drug Administration (FDA) for use in various therapeutic devices, PLGA is engineered for precise medical functions. Its ability to dissolve predictably allows it to deliver medication or act as a temporary scaffold for tissue repair, making it an important component in implantable and injectable medical technologies.
What is PLGA
PLGA is classified as a co-polymer, a large molecule formed by linking two different types of smaller, repeating units together. The two building blocks are Lactic Acid (LA) and Glycolic Acid (GA), which are simple organic molecules found naturally in the body as metabolic products. The synthesis of PLGA typically involves ring-opening polymerization, where the cyclic dimers of lactic acid (lactide) and glycolic acid (glycolide) are linked together. This chemical reaction creates long, linear chains where the LA and GA units are generally arranged randomly. These chains are connected by ester linkages, which determine the polymer’s eventual fate in an aqueous environment.
The Mechanism of Biodegradation
PLGA’s utility in medicine is defined by its controlled biodegradation, which occurs through hydrolysis. When a PLGA device is placed inside the body, water molecules from the surrounding biological fluid penetrate the polymer matrix. This water attacks and cleaves the ester bonds linking the Lactic Acid and Glycolic Acid units along the polymer backbone. This cleavage gradually breaks the long polymer chains into progressively smaller fragments, a phenomenon known as bulk erosion. The breakdown products are the original monomers, Lactic Acid and Glycolic Acid. Lactic acid is easily metabolized into carbon dioxide and water, while glycolic acid is similarly cleared through the kidneys.
Customizing PLGA Properties
Scientists use two primary elements to fine-tune PLGA’s behavior: the ratio of its constituent monomers and the overall length of the polymer chains. Manipulating the balance between Lactic Acid (LA) and Glycolic Acid (GA) directly influences the material’s hydrophilicity, or its affinity for water. Glycolic Acid units are more hydrophilic than Lactic Acid units, making them more water-repellent.
A PLGA copolymer composed of a 50:50 ratio of LA to GA exhibits the fastest degradation rate because it is the most hydrophilic composition and absorbs water quickly. Conversely, increasing the proportion of Lactic Acid, such as in a 75:25 or 85:15 ratio, makes the polymer more hydrophobic, delaying water penetration and slowing the degradation process. This ratio adjustment allows engineers to determine the polymer’s expected lifespan inside the body, which can range from a few weeks to over a year.
The second element is the polymer’s molecular weight, which refers to the total length of the polymer chains. Polymers with a higher molecular weight are composed of longer chains, resulting in greater mechanical strength and a slower degradation rate. Longer chains require more time for hydrolysis to break them down into fragments small enough to become soluble and diffuse away.
Core Applications in Medicine
PLGA’s combination of controlled biodegradability and tunable properties makes it a preferred material for advanced medical applications. One significant use is in controlled drug release systems, where the polymer acts as a microscopic reservoir for therapeutic agents. Drugs are encapsulated within PLGA microparticles or nanoparticles, which are then injected or implanted into the body.
The gradual hydrolysis of the PLGA matrix dictates the rate at which the drug is released, allowing for sustained dosing over extended periods. This sustained release eliminates the need for frequent injections, improving patient compliance and managing drug concentration levels more effectively. Examples include FDA-approved injectable microspheres, such as Lupron Depot, which delivers medication for prostate cancer over a prolonged duration.
PLGA is also widely used in tissue engineering to create temporary, three-dimensional scaffolds that promote tissue regeneration. These porous structures provide a framework for cells to attach, proliferate, and synthesize new tissue. As the body naturally rebuilds the damaged area, the PLGA scaffold safely degrades, transferring the mechanical load to the newly formed tissue without the need for surgical removal. Furthermore, the polymer is routinely employed in the fabrication of absorbable surgical sutures and orthopedic fixation devices, providing temporary structural support before dissolving.