Poly(L-lactide) (PLLA) is a biodegradable polymer derived from lactic acid, a naturally occurring organic acid. Over recent decades, PLLA has garnered significant attention in the field of drug delivery due to its biocompatibility, biodegradability, and versatile physical properties. Its ability to break down into non-toxic byproducts that can be metabolized and excreted by the human body makes it an attractive material for various medical applications. The polymer's mechanical strength, thermal stability, and adjustable degradation rate further enhance its utility, allowing it to be tailored for specific therapeutic needs. In drug delivery, PLLA's primary advantage lies in its potential to improve the pharmacokinetics and biodistribution of therapeutic agents, ensuring a controlled and sustained release of drugs at the target site. This feature is particularly crucial for maintaining therapeutic efficacy while minimizing side effects, which is a common challenge in conventional drug delivery methods. One of the key benefits of using PLLA in drug delivery systems is its capacity to form various structures such as nanoparticles, microspheres, and implants, each offering unique advantages for different therapeutic contexts. Nanoparticles made from PLLA, for example, can encapsulate a wide range of drugs, including hydrophilic and hydrophobic molecules, proteins, and nucleic acids. These nanoparticles can enhance drug stability, reduce systemic toxicity, and improve targeting efficiency by modifying their surface with ligands or antibodies that recognize specific cell types or tissues. PLLA nanoparticles are particularly beneficial for cancer therapy, where targeted delivery of chemotherapeutic agents can significantly reduce the damage to healthy cells and improve the overall treatment outcome. Moreover, the small size of nanoparticles allows them to penetrate tissues more effectively, providing a more localized and potent therapeutic effect. PLLA microspheres, on the other hand, are often used for the sustained release of drugs, providing a steady therapeutic level over extended periods. This is particularly beneficial for chronic conditions requiring long-term medication, such as diabetes, where constant drug levels are essential to manage the disease effectively. The ability of PLLA to degrade slowly over time ensures that the drug is released gradually, maintaining its concentration within the therapeutic window and reducing the frequency of administration. This not only improves patient compliance but also enhances the overall quality of life for individuals with chronic illnesses. Additionally, PLLA-based implants can be designed to release drugs at a controlled rate directly at the site of action, which is advantageous for treating localized conditions like bone infections or cancerous tumors. These implants can be engineered to fit the specific anatomy and pathology of the patient, offering a personalized approach to treatment.
Figure 1. Nanoparticles based on poly-L-lactic acid (PLLA) and polyglycerol adipate (PGA) to encapsulate usnic acid (UA). (Brugnoli B, et al.; 2024)
The versatility of PLLA extends beyond its physical forms to its functional modifications. Through copolymerization or blending with other biodegradable polymers like poly(glycolic acid) (PGA) or poly(caprolactone) (PCL), the properties of PLLA can be fine-tuned to achieve desired degradation rates and mechanical characteristics. This adaptability allows researchers and medical practitioners to design drug delivery systems that can meet the specific requirements of different medical conditions. For instance, the incorporation of PEG (polyethylene glycol) into PLLA can enhance its hydrophilicity and biocompatibility, making it more suitable for injectable formulations. PEGylation not only improves the solubility and stability of the drug delivery system but also reduces the potential for immune recognition and clearance, thereby extending the circulation time of the therapeutic agents in the body. Furthermore, the surface modification of PLLA-based drug delivery systems with targeting moieties or stimuli-responsive elements can facilitate the development of advanced therapeutic strategies. Targeting moieties such as peptides, antibodies, or small molecules can be attached to the surface of PLLA nanoparticles or microspheres to direct them to specific cell types or tissues, thereby enhancing the precision and efficacy of drug delivery. For example, folate-conjugated PLLA nanoparticles can selectively target cancer cells that overexpress folate receptors, improving the uptake of chemotherapeutic agents and reducing off-target effects. Stimuli-responsive elements, on the other hand, can trigger drug release in response to specific physiological or external stimuli such as pH changes, temperature variations, or the presence of certain enzymes. This approach allows for the on-demand release of drugs, providing a more controlled and effective treatment regimen.
PLLA's potential in drug delivery is further exemplified by its application in gene therapy. The polymer can be used to encapsulate and protect genetic material, such as DNA or RNA, from degradation by nucleases in the body. PLLA-based nanoparticles or microspheres can facilitate the intracellular delivery of these genetic materials, enabling the expression of therapeutic genes or the silencing of disease-causing genes. This is particularly promising for treating genetic disorders, cancer, and infectious diseases, where conventional drug therapies may fall short. By providing a safe and efficient means of delivering genetic material, PLLA opens up new avenues for advanced therapeutic interventions. In addition to its role in drug delivery, PLLA has also been explored for its use in tissue engineering and regenerative medicine. PLLA scaffolds can provide a temporary structure for cell attachment and growth, promoting tissue regeneration in damaged or diseased areas. The biodegradability of PLLA ensures that the scaffold will gradually degrade as the new tissue forms, eliminating the need for surgical removal. This property makes PLLA an attractive material for applications such as bone and cartilage repair, where it can support the regeneration of healthy tissue while maintaining the structural integrity of the affected area. Furthermore, PLLA's compatibility with a wide range of bioactive molecules allows for the incorporation of growth factors, cytokines, and other therapeutic agents into the scaffold, enhancing the regenerative process.
Alternate Names:
Poly(L-lactide)
Poly(L-lactic acid)
L-lactide polymer
PLLA polymer
References:
1. Dai Y, et al.; Recent advances in PLLA-based biomaterial scaffolds for neural tissue engineering: Fabrication, modification, and applications. Front Bioeng Biotechnol. 2022, 10:1011783.
2. Brugnoli B, et al.; Nanostructured Poly-l-lactide and Polyglycerol Adipate Carriers for the Encapsulation of Usnic Acid: A Promising Approach for Hepatoprotection. Polymers (Basel) . 2024, 16(3):427.
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