The biodegradable, biocompatible polymer Poly(D-lactide) is part of the poly(lactic acid) (PLA) family and is very popular in drug delivery systems. It's also biodegradable, like corn or sugarcane, and thus green compared to polymers that are artificial, which is great for pharma and biomedical use. Because of its specificity — it is degraded into lactic acid, an endogenous metabolite, and it can be a microparticle or nanoparticle — it provides a perfect substrate for the controlled dispensing of a diverse therapeutic spectrum. Poly(D-lactide) has also been extremely biocompatible and biodegradable so it has been extensively employed for controlled release drug delivery, tissue engineering and injections. This polymer's nexus of drug delivery technologies has made it a key ingredient in the evolution of sustained-release delivery, particularly for poorly soluble drugs and proteins. The main strength of Poly(D-lactide) for delivering drugs is that it is controlled in degradation. When released into the body, Poly(D-lactide) slowly hydrolyses to lactic acid which is then converted by natural process in the body. This regulated rate of degradation permits the long-term dissolution of encapsulated drugs (up to several days or months, depending on formulation and therapeutic efficacy). In cancer treatment, for example, Poly(D-lactide) can be used to make drug-loaded nanoparticles or microspheres that hold chemotherapy drugs inside them, slowly and over time releasing the drug so that therapeutic levels can be maintained at the site of action. This controlled release decreases the frequency of dose and side effects and a more efficient and convenient regimen for patients. This freedom to change the degradation rate of Poly(D-lactide) also makes it possible to develop customised drug delivery systems in which the release profile could be modified to meet the requirements of individual patients or diseases. Poly(D-lactide) isn't just used for controlled release applications, but also for targeted delivery of drugs. Modifying the surface of the polymer or affixing targeting ligands, including peptides, antibodies or small molecules, allow Poly(D-lactide) to be targeted to tissues or cells to boost drug efficacy without the occurrence of systemic side effects. It's especially true in diseases such as cancer, where the drug has to be targeted only to the tumour tissue without damage to healthy cells. Poly(D-lactide)'s biocompatibility and biodegradability further expand its potential for these specific drug delivery strategies since the polymer itself doesn't lead to toxic reactions or linger in the body after the release of the drug. Such properties make Poly(D-lactide) ideal for designing advanced drug delivery systems including nanoparticles, micelles and microspheres that deliver targeted therapy and controlled release in one compound.
Figure 1. Crystal structures of different Poly(D-lactide). (Hideto Tsuji, et al.; 2023)
The Poly(D-lactide) uses in drug delivery aren't limited to the oral or intravenous drug delivery. Use in nanoparticles, microparticles and other highly efficient drug delivery systems has created new possibilities to enhance drug bioavailability and targeting. Nanoparticles made from poly(D-lactide) can hold a wide variety off therapeutic substances: small molecules, proteins, peptides, nucleic acids, and even vaccines. When added to Poly(D-lactide) nanoparticles, not only do these agents prevent them from oxidation in the short term, but their release can be monitored over time. This is especially useful for medications that are unstable in the blood or need a longer release time to be therapeutically effective. Poly(D-lactide) products, for instance, can be used to dispense anticancer medications, antiviral drugs and growth factors that would otherwise need frequent administration if they were available in the form of a tablet. Poly(D-lactide) can be employed for drug encapsulation as well as in micelles for hydrophobic drugs with low aqueous solubility. Its amphiphilic properties allow the Poly(D-lactide) to be used to create micelles in water and the micelle's hydrophobic interior is designed to encapsulate insoluble medications so they become more soluble and bioavailable. Poly(D-lactide) micelles are especially advantageous for lipophilic drugs, which are difficult to give via standard route. Moreover, the surface of Poly(D-lactide) micelles can be targeted with targeting ligands or modified to maximise the capacity of drug-loading, hence improving the drug's therapeutic performance. The micellar systems have become increasingly popular in delivering chemotherapy, antimicrobial agents and other bioactive compounds, and provide a cost-effective solution to make drugs that would otherwise be hard to deliver solubilise and deliver them. Poly(D-lactide) also becomes a major part of tissue-engineering scaffolds and regenerative medicine. The polymer itself breaks down into lactic acid, which the body can process by itself, and so is a great candidate for scaffolds that aid in the regeneration of tissues. Poly(D-lactide) can be incorporated with other biomaterials like collagen or growth factors to create scaffolds not only for structural support of the tissue growth, but for delivery of living molecules that enhance regeneration. This can be especially useful in areas like repair of bone and cartilage where Poly(D-lactide) scaffolds can act as an anti-inflammatory temporary matrix that will support cell and tissue growth and also deliver therapeutics for wound healing. Because these agents are selectively released over time and because the polymer breaks down without toxic side effects, Poly(D-lactide) scaffolds are a wonderful choice for a multitude of tissue engineering uses.
But even with all its therapeutic upsides, Poly(D-lactide) has some kinks to iron out before it goes mainstream in the clinic. While Poly(D-lactide) is biodegradable, degradation can be affected by polymer molecular weight, drug delivery formulation and body environment. Poly(D-lactide) nanoparticles, for example, break down slower – a plus for long-term absorption, but also potentially preventing absorption of the drug, sometimes with poor dosing. Degradation of Poly(D-lactide) must be observed and prepared for. In polymer chemistry innovations like copolymers or polymer-polymer combination (e.g., poly(ethylene glycol) (PEG) or poly(lactic-co-glycolic acid) (PLGA)) are being used to control the degradation rate and release characteristics of Poly(D-lactide) based delivery systems. The second issue with Poly(D-lactide) is its relatively low drug-loading capacity. While the polymer is capable of containing many different therapeutic molecules, because Poly(D-lactide) is so hydrophobic, it's not recommended to carry much hydrophilic drugs or biomolecules. This limitation has pushed the research on new formulations and methods for maximizing drug-loading efficiency. The combination of Poly(D-lactide), for instance, with surfactants, co-polymers, or carriers like lipids or proteins will increase the encapsulation and release of the drug. Further, surface modification methods like adding hydrophilic segments or targeting ligands can enhance the polymer's drug-delivery performance and enable it to be applied to more therapeutics. Going forward, Poly(D-lactide) drug delivery platforms will become an even bigger part of personalized medicine. Having better understanding of the molecular and cellular process that drives disease, it's become more appealing to build targeted drug delivery systems for particular disease states or specific patient requirements. The programmability of Poly(D-lactide) – via changes to the molecular weight of the polymer, targeting moieties, or hybrid delivery systems – means it is ideally suited for precision therapies. The creation of pH, temperature or enzyme-responsive drug delivery systems that would release drugs depending on changes in pH, temperature or even enzyme levels is another area where Poly(D-lactide) has a great deal of promise. These advances will further improve Poly(D-lactide) delivery of drugs for better treatment outcomes and reduced patient side effects.
Alternate Names:
Poly(DL-lactide)
Poly(D-lactic acid)
Poly(DL-lactic acid)
D-Lactide Polymer
D-PLA (Poly-D-lactic acid)
D-Lactide-Based Polymer
References:
1. Hideto Tsuji, et al.; Comparative study on the effects of incorporating poly(d,l-lactide) and solvent on stereocomplex crystallization and homocrystallization in unconstrained and constrained poly(l-lactide)/poly(d-lactide) systems. Polymer Journal. 2023, volume 55, pages75–84.
Datasheet
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