Introduction
The poly(D-lactide) (PDLA) is a critical biodegradable polymer for delivery systems. PDLA is biocompatible and biodegradable, and thus a perfect candidate for drug delivery. It can be hydrolyzed into lactic acid by the body and then, finally, metabolised to carbon dioxide and water by the human body without causing any poison. PDLA has modulable drug release activity on drug delivery systems. It can be adjusted in terms of molecular weight, copolymer composition and shape so that the release pattern can be controlled for better controlled release. Not only can PDLA be used as a drug carrier, but it can also be copolymerized with other polymers like polyethylene glycol (PEG) to create a polymer composite material with better drug stability and biocompatibility. PDLA can also be used to engineer novel drug delivery vehicles including microparticles and nanoparticles to enhance drug's cell endocytosis and cross-biological barrier capacity. PDLA is also a biodegradable material, which makes it very important for reducing medical waste and conserving the planet. Its decomposition products are harmless and easily digested by the body — the requirements of green chemistry and sustainable development. For this high performance, PDLA has been validated in many clinical environments, such as tissue engineering scaffolds, sustained-release drug delivery systems and implantable drug delivery systems. Such uses illustrate the promise of PDLA in contemporary medicine. Thus, research on the use of PDLA as a carrier for drugs is not only beneficial to the creation of novel drug delivery systems, but also of major scientific interest in terms of enhancing drug treatment, minimizing side effects, and fostering sustainability.
Figure 1. Polylactic acid-based microparticles for drug delivery. (Vlachopoulos A, et al.; 2022)
Structural Characteristics of Poly (D-lactide)
Poly (D-lactide) is linear D-lactide monomer polymerisation. It is a cyclic lactone derived from dehydration condensation of two D-lactide molecules. D-lactide is a lactide isomer, its molecular formula is C6H8O4, it forms transparent streaks or needle crystals, has a melting point between 93 and 95°C, and usually is 99.5% pure. Polymerization of poly (D-lactide) can change the molecular weight and molecular weight distribution of the polymer by changing the polymerisation reaction conditions. For example, it could perform the polymerisation reaction at lower reduced pressure to get a higher molecular weight poly (D-lactide) with viscosity-average molecular weight of up to 1.43X105.
The poly(D-lactide) fabrication is done mainly by ring-opening polymerization process which keeps the molecular weight and molecular weight distribution of the polymer unchanged to cater to various applications. You can, for example, manipulate the mix of D-lactide to diol monomers being introduced to modify the product weight. In addition, the ring-opening polymerisation reaction of D-lactide is usually catalysed with a catalyst such as stannous octoate to make the polymerisation more effective. Poly(D-lactide) easily solubilised and crystallised, glass transition temperature 65-75°C, melting point 95-95°C. Since poly(D-lactide) is a unique molecular type and the rate at which it can be degraded varies with pH, temperature and humidity, biomedical use of this material is potentially very wide.
Advantages of Drug Delivery
Poly(D-lactide) (PDLA) has many benefits in the area of drug delivery systems, which are much in demand in biomedicine. Here are its main advantages:
- Biodegradability and Biocompatibility
Poly(D-lactide) is biocompatible and biodegradable. It can be broken down into harmless molecules in the body like lactic acid by hydrolysis process, so that it cannot accumulate and be toxic long term. This feature makes PDLA a safe drug carrier material, especially in treatments that require drug release over a long period of time.
- Controllable Drug Release Characteristics
The drug-release profile of PDLA is manipulated by altering its molecular weight and structure (grafting, copolymerisation). For instance, by changing the molecular weight and structure of the polymer, a prolonged or controlled release of the drug is possible, thus extending the life of the drug. This property is useful for applications where prolonged drug delivery is needed to sustain therapeutic effects.
- Good Drug Loading Capacity and Biofilm Penetration Ability
PDLA loads small molecules, proteins and nucleic acids. Additionally, if they can be modified in terms of surface conditions (eg, hydrophilicity or hydrophobicity), the drug's cross-biological-membrane behavior can be optimised, making it a more efficient delivery system. This feature makes PDLA broadly usable for targeted drug delivery.
Poly(D-lactide) can be used both internally and externally for a stable drug delivery and less prone to drug degradation. This helps the drug remain stable and active during administration, which increases therapeutic effectiveness.
Application of Poly(D-lactide) in Drug Delivery
The applications of Poly(D-lactide) include drug delivery (mainly for anticancer), protein/gene, and local delivery).
Poly(D-lactide) is commonly used in controlled release systems for anticancer agents, as it is biocompatible and degradable. Drugs like doxorubicin (DOX) could be packaged in microspheres or nanoparticles made with poly(D-lactide) to be released over the long term and targeted at the target of the drug's delivery, minimizing drug side effects and increasing efficacy. So poly(D-lactide)-based drug-loaded microspheres and nanoparticles, for instance, have been clinically shown to treat tumours. With control of the release rate, action time of the drug in the body can be successfully increased and toxic burdens on normal tissues minimized.
- Protein and Gene Drug Delivery
It is also employed to carry biomacromolecule drugs like vaccines, antibodies and nucleic acid drugs (ie siRNA, mRNA, etc.). Because it is biocompatible and stable, poly (D-lactide) can be added to a carrier to package these biomacromolecules for enhanced stability and targeting in the body. By combining with nucleic acid drugs, for instance, PLGA-PEG-MAL nanoparticles could do the work of gene therapy without the side effects of drugs.
Poly (D-lactide) works well in local therapy, too. It can increase therapeutic effect by slow local release of medications, for example, during healing of wounds and bone fractures. This local delivery technology is more effective for less systemic side effects and better local therapeutics.
Poly (D-lactide) also has promise in the delivery of eye drugs and vaccines. Poly (D-lactide) can be made to produce retinal protection nanoparticles, for instance, for the purposes of drug permeability and stability in ophthalmic care. Furthermore, it is also used in vaccine delivery systems to boost immunity and prolong the life of vaccines by capturing antigens.
As a biodegradable polymer, poly (D-lactide) has broad promise in drug delivery, particularly in increasing drug efficacy, decreasing side effects and achieving targeted delivery.
Reference
- Vlachopoulos A, et al.; Poly(Lactic Acid)-Based Microparticles for Drug Delivery Applications: An Overview of Recent Advances. Pharmaceutics. 2022, 14(2):359.
