How Does The Nano-Drug Delivery System Achieve Lymphatic Targeting
Physiological characteristics of lymph
The lymphatic system consists of lymphatic channels, lymphoid organs, and lymphoid tissues. Colorless and transparent lymph fluid flows in the lymph system. Lymphatic vessels include capillary lymphatic vessels, lymphatic vessels, and lymphatic ducts. Lymphatic organs include lymph nodes, thymus, and spleen. When blood flows through the capillaries, part of the liquid substance seeps into the interstitial space, forming interstitial fluid. Most are absorbed into the blood through the venous ends of the capillaries, and a small part of the water content and the interstitial fluid of macromolecules enter the capillary lymphatic vessels to become lymph. The lymph flows to the heart along the lymph vessels at all levels, and after filtering by several lymph nodes on the way, it finally flows into the vein, so the lymphatic system can be regarded as the auxiliary structure of the vein. The lymphatic system assists the venous return of body fluids, and the lymphoid organs and lymphoid tissues in the system have the functions of generating lymphocytes, filtering lymph fluid and participating in immune responses.
Clinical studies have shown that the lymphatic system is the site of many diseases, such as metastatic tuberculosis, cancer, and filariasis. Lymphatic metastasis is the most common metastatic pathway for malignant tumors, and is the main cause of postoperative recurrence and death. Systemic chemotherapy and radiotherapy have poor or no significant effect on lymphatic metastases in malignant tumors. Utilizing the characteristics of lymphocytes phagocytosing macromolecular and particulate materials, anticancer drugs and carrier materials are made into microparticles or macromolecules through physical and chemical methods. After local injection and administration, the drug is drained to the lymph node metastasis through lymphatic drainage to achieve the purpose of targeted and sustained release administration of the lymph node metastasis. Lymphoid tissue is indistinguishable from the adipose tissue that covers it in color and shape. Lymph node staining before surgery is also a target for lymphoid targeting. After intravenous administration, the particles in the colloidal range are mainly engulfed by the liver and kidney mononuclear macrophage system, and it is difficult to reach other parts. Therefore, to obtain lymphatic targeting, oral, eye or subcutaneous administration may be appropriate route of administration.
Lymphatic targeting nano–drug delivery system
1). Activated carbon
Activated carbon has a strong lymphatic tendency, and was originally used for local injection to blacken regional lymph nodes to guide lymph dissection during surgery. The activated activated carbon particles can absorb a variety of chemotherapeutic drugs due to the porous honeycomb structure. After local injection of activated carbon that physically adsorbs anticancer drugs, it has a strong affinity for cancer cells and lymphoid tissues. It adheres to the surface of metastatic cancer cells to form a fibrous network. The drug is slowly released according to the concentration gradient and maintains a dynamic balance with the surrounding free drug concentration for a long time. The dynamic balance can significantly reduce the toxic and side effects of chemotherapy drugs.
2). Emulsion
Mitomycin is made into an emulsion that can be preferentially transported through the lymph, which is administered intraperitoneally or intramuscularly. It is found that the drug could selectively accumulate in the local lymphatic system. The effect of O / W emulsion is better than W / O emulsion, both of which are superior to aqueous solutions.
3). Liposomes
Liposomes can be selectively transported into lymphatic tissue after intraperitoneal, intramuscular or subcutaneous injection. Physical properties such as liposome composition, size, surface charge, and route of administration may affect the uptake of the lymphatic system and the retention time of liposomes. Small particle size liposomes are more likely to pass through the lymph nodes, while larger liposomes may be retained by physical filtration. After entering the lymphatic system, liposomes will pass through a series of lymph channels and encounter lymph nodes. At this time, some liposomes are retained, and the main mechanism is phagocytosis by macrophages. In addition, modified liposomes can increase lymphoid targeting capabilities, such as immunoliposomes, PEGylated liposomes, and galactosylated liposomes.
4). Nanoparticle
Polyethyl cyanoacrylate, polyhexyl cyanoacrylate and other materials can be made into lymph targeting nano preparations. Polyhexyl cyanoacrylate nanoparticles can be transported via lymphatic pathway or peritoneal cavity after intraperitoneal administration, and can be used to treat tumors. Modification of nanoparticles may enhance uptake of lymphatic vessels and nodes. For example, moderately hydrophilic modification of the surface of the nanoparticle is beneficial for targeting lymphocytes, but “long-cycle” nanoparticles that are too hydrophilic or even invisible for modification may not be good for lymphoid targeting. In addition, solid lipid nanoparticles (SLN) can also be used for lymphatic targeting.
5). Nanocapsule
The surface of the nanocapsules is a polymer coating and the drug is encapsulated inside. Vegetable oils or semi-synthetic long-chain fatty acid triglycerides are preferred for nanocapsule cores. Biodegradable polymers such as polyalkylcyanoacrylates and polylactic acid compounds are often used as outer coatings. The PLGA nanocapsules of docetaxel are prepared by spray drying process. After oral administration, the absolute bioavailability is increased by 276% compared with the docetaxel solution. The fluorescence imaging system shows that the nanocapsules are aggregated in the lymphatic system.