PLGA is a biodegradable polymer formed by random polymerization of two monomers, lactic acid and glycolic acid. It has good biocompatibility, non-toxicity, and good encapsulation of nanoparticles, and is widely used in the fields of pharmaceuticals and medical engineering materials.
Figure 1. PLGA-based nanoparticles.(Danhier F, et al.; 2012)
Application of PLGA nanoparticles in tumor treatment
Existing studies have shown that PLGA nano-drug delivery technology has important applications in tumor treatment. Because researchers can improve the stability and bioavailability of anti-tumor drugs and reduce the side effects of drugs by encapsulating anti-tumor drugs in PLGA nanoparticles. After being taken up by tumor cells, PLGA nanoparticles can release drugs into tumor cells and improve the local efficacy of drugs. In addition, researchers can also achieve targeted drug delivery and increase drug accumulation in tumor tissues by changing the properties of PLGA nanoparticles.
Tumor-aggregating nanocarriers first work through the high permeability and retention effect (ERP) effect of solid tumors. The microvascular endothelial gaps in normal tissues are dense and structurally intact, and macromolecules and lipid particles cannot easily penetrate the blood vessel wall. However, solid tumor tissues have abundant blood vessels, wide blood vessel wall gaps, poor structural integrity, and lack of lymphatic return, resulting in macromolecule-type Substances and lipid particles have selective high permeability and retention. This phenomenon is called the tumor-enhanced permeability and retention effect, or the EPR effect for short. PLGA nanoparticles have the characteristics of good stability and long vascular circulation time, and are particularly suitable for passive targeted therapy of tumors. PLGA-coated chemotherapy drugs, such as doxorubicin, paclitaxel, cisplatin, curcumin, etc., all use this passive targeted therapy strategy to increase anti-tumor activity, prolong circulation time, and avoid contact between the drug and the blood to improve the drug stability. For example, the half-life of PEGylated PLAG nanoparticles loaded with doxorubicin was 3.7 times higher than that of the free drug. In passive drug targeting therapy, the phagocytosis effect will shorten the circulation time of the drug in the blood, while the PEGylated PLGA nanoparticles prevent the phagocytosis effect on the nanoparticles due to the concealment effect of PEG, thus prolonging the circulation time. In addition, wrapping anti-cancer drugs in biocompatible polymers and using passive targeted therapy can not only improve the anti-tumor effect, but also significantly reduce the side effects of the drugs.
Application of PLGA Nanodrug Carrier in Vaccine Delivery
PLGA nano drug delivery technology has important applications in vaccine delivery. By wrapping vaccine antigens in PLGA nanoparticles, the stability and immune effect of the vaccine can be improved. The vaccine can be stably wrapped to prevent degradation and inactivation of the vaccine. At the same time, the delivery efficiency and immune effect of the vaccine can be improved. By being taken up by immune cells, the vaccine antigen is released into the cells, activating immune cells and improving the immune effect of the vaccine. In addition, by changing the properties of PLGA nanoparticles, targeted delivery of vaccines can be achieved and the accumulation of vaccines in immune tissues can be improved.
The following introduces four practical applications of PLGA in vaccine delivery:
1. Wrap different types of vaccines in particles, such as virus-like particle vaccines, protein vaccines, etc. These nanoparticles can improve the stability of vaccines and extend their immune effects through controlled release.
2. Vaccine microspheres: PLGA microspheres can be used to prepare sustained-release vaccines. The researchers wrapped the vaccine in PLGA microspheres and achieved sustained release of the vaccine through slow degradation of the microspheres. This sustained-release vaccine can improve the stability of the vaccine and prolong the immune effect of the vaccine. Such as PLGA nanospheres with hepatitis B surface antigen (HBsAg) as the antigen. The biomimetic material dopamine is used for self-polymerization coating modification, and antigens and immune stimulants are successfully carried on the surface of nanospheres. Their size is similar to that of pathogens, and their structure and composition can also simulate pathogens well. Cytotoxicity experiments and preliminary safety evaluation show that the biocompatibility is good. The nanospheres can well simulate the infection process of pathogens, induce the production of inflammatory cytokines and chemokines at the injection site, induce a strong antigen-specific cellular immune response, and at the same time increase the secretion level of antigen-specific antibodies.
3. Scaffold-vaccine composite material: Researchers composited PLGA scaffolds with vaccines to prepare an implantable vaccine delivery system. This composite material can achieve long-term release of vaccines through the implantation of scaffolds and improve the immune effect of vaccines. For example, PLGA scaffolds combined with influenza vaccines can achieve vaccine release for several months.
4. Adhesive-vaccine complex: Researchers compounded PLGA with an adhesive to prepare a vaccine delivery system that can adhere to mucosal surfaces. This complex can increase the residence time of the vaccine on the mucosal surface and improve the immune effect of the vaccine. For example, PLGA is combined with gel to prepare a flu vaccine delivery system that can adhere to the nasal mucosa. And through five days of observation and control, the film doped with PLGA nanoparticles showed superior advantages in transport across the mucosal barrier, with higher drug bioavailability (approximately 3.5 times higher than that observed with oral administration) and oral administration. Therapeutic efficacy in mucositis model (approximately 6.0-fold improvement in wound closure).
The application of PLGA nano drug delivery technology in vaccine delivery can also achieve better immune effects through combined vaccines. By encapsulating different vaccine antigens in PLGA nanoparticles, the joint delivery of multiple vaccines can be achieved and the immune effect can be improved. In addition, PLGA nano-drug loading technology can also combine vaccines with immune adjuvants, photothermal therapy and other treatment methods to achieve multiple immune effects and improve the immune effect of vaccines.
Application of PLGA Nanodrug Loading in Bone Tissue Engineering
PLGA nanodrug loading technology has important applications in bone tissue engineering. By wrapping bone tissue engineering materials such as growth factors and cells in PLGA nanoparticles, the stability and biological activity of the materials can be improved. PLGA nanoparticles can be taken up by bone cells and release growth factors, cells, etc. into bone tissue to promote the growth and repair of bone tissue. In addition, PLGA nanodrug-carrying technology can also achieve targeted delivery of bone tissue engineering materials by changing the properties of PLGA nanoparticles, and achieve joint release of multiple materials, improve the growth and repair effect of bone tissue, and improve the accumulation effect of materials in bone tissue. It has significant effects in bone regeneration, bone defect repair, and fracture healing.
Depending on the type of polymeric biomaterial used and its intended application, cross-linking may be required to ensure the stability of the material under physiological conditions. The choice of cross-linking strategy also has a direct impact on the degradation behavior of the material, as some cross-links are cleaved by enzymatic or hydrolytic mechanisms, thereby promoting degradation and potentially reorganization of the structure. Cross-linkers or chemical initiators added to polymeric materials must themselves be biocompatible at specific doses or extractable prior to contact with living cells or tissues.
The application of PLGA nanodrug-carrying technology in bone tissue engineering can also achieve better results through combined treatment. In addition, combining it with bioceramics, bioactive substances, etc. can achieve multiple therapeutic effects and improve the comprehensive effect of bone tissue engineering.
References
- Danhier F, et al.; PLGA-based nanoparticles: an overview of biomedical applications. J Control Release. 2012, 161(2):505-22.
- Sadat Tabatabaei Mirakabad F, et al.; PLGA-based nanoparticles as cancer drug delivery systems. Asian Pac J Cancer Prev. 2014;15(2):517-35.
