{"id":749,"date":"2021-08-27T07:44:06","date_gmt":"2021-08-27T07:44:06","guid":{"rendered":"http:\/\/www.cd-bioparticles.net\/blog\/?p=749"},"modified":"2023-07-18T09:10:39","modified_gmt":"2023-07-18T09:10:39","slug":"protein-peptide-drug-lung-inhalation-nano-preparation","status":"publish","type":"post","link":"https:\/\/www.cd-bioparticles.net\/blog\/protein-peptide-drug-lung-inhalation-nano-preparation\/","title":{"rendered":"Protein Peptide Drug Lung Inhalation Nano Preparation"},"content":{"rendered":"

Pulmonary administration has great advantages as a non-invasive route of administration of protein and peptide drugs. The human respiratory tract has a large surface area, which can avoid the first pass effect of the liver. In addition, the viscosity of the epithelial cell barrier is low, and there is a large amount of potential vasculature, low proteolytic activity and low acidity. Compared with the gastrointestinal tract, there is a thinner mucus layer, so the lungs are suitable for local and systemic administration. However, the mucosa of the respiratory tract is very tight and complex, and it is difficult for macromolecular drugs to penetrate. In fact, a single macromolecule is difficult to cross the epithelial cells, is easily degraded by enzymes in the respiratory tract, and is easily cleared by macrophages or mucociliary hairs, so the bioavailability is very low. For example, the systemic bioavailability of insulin nasal administration is very low, only about 1%, and it is difficult to exert a therapeutic effect. The preparation of protein peptide drugs into nano preparations and then pulmonary administration is an effective method to improve the bioavailability of biotechnology drugs. At present, there are many kinds of protein peptide drugs in the lung inhalation nano-formulations that have proved to be effective.<\/p>\n

\"\"
Figure 1. Developing inhaled protein therapeutics for lung diseases.<\/figcaption><\/figure>\n

Insulin
\nInsulin liposomes<\/a> with average particle diameters of 1.91\u03bcm and 2.08\u03bcm were prepared by thin film ultrasonic dispersion method and reverse phase evaporation method.\u00a0After instillation into the rat trachea, the two liposomes had significant blood glucose lowering effects,\u00a0the minimum blood glucose concentration is less than 5%, the time to reach the lowest blood sugar level is about 180 minutes.\u00a0In comparison, intratracheal instillation of the same dose of insulin solution can also significantly reduce blood glucose levels.\u00a0The minimum blood glucose concentration is about 20%, and the time to reach the minimum blood glucose level is about 120 minutes.\u00a0Therefore, liposomes have the effect of promoting the absorption of the islet cord from the lungs.\u00a0The relative bioavailability of insulin liposome pulmonary administration and subcutaneous injection of insulin solution is 37%, while that of insulin solution pulmonary administration is 29%.\u00a0Insulin liposomes and physical suspensions of insulin and blank liposomes have no significant difference in promoting the pulmonary absorption of insulin, enhancing the hypoglycemic effect and prolonging the action time.\u00a0Therefore, the surface activity of liposomal phospholipids and the activation of alveolar surface macrophages are the main factors that promote the absorption of insulin in the lungs.<\/p>\n

Calcitonin
\nChitosan-modified nanoparticles<\/a> have the advantages of bioadhesiveness, slower clearance rate, and longer drug effect time.\u00a0Taking calcitonin as a model drug, PLGA nanoparticles are prepared by the emulsification-solvent diffusion method, and then modified with chitosan to obtain chitosan-modified calcitonin PLGA nanoparticles with a particle size of 650nm and a particle size of about 6.5 \u03bcm after atomization, the effective part deposition rate is 51.3%.\u00a0It has a significant effect on reducing the blood calcium concentration, reducing the blood calcium concentration to 80% of the total calcium content, and the pharmacological effect time can be extended to 24h, which has significant advantages compared with the nanoparticles that are not modified by chitosan.<\/p>\n

Thymopentin
\nThe spray-drying technology is used to prepare lung inhalation microspheres composed of solid lipid nanoparticles loaded with thymopentin.\u00a0The surface of the microspheres is porous, with a particle size of 4.8 \u03bcm, a bulk density as low as 0.48 g\/cm3, and a solid density of 0.71 g\/cm3.\u00a0The microspheres have good inhalation characteristics, the emptying rate is 85.0%, the effective site deposition rate is 61.6%, and they can be effectively distributed into the alveoli.\u00a0Nanoparticles and thymopentin can maintain good stability during the preparation process.\u00a0This new type of microsphere has suitable inhalation characteristics and is a pulmonary drug delivery system with good application prospects.
\nInterleukin
\nInterleukin 2 is a commonly used immunopotentiator for adjuvant treatment of tumors and immunodeficiency diseases.\u00a0It is usually administered by subcutaneous injection, but it is easy to cause swelling at the injection site.\u00a0Aerosolized IL-2 liposomes and blank liposomes with a particle size of 1.1 \u03bcm to immunodeficiency patients and hepatitis patients.\u00a0After 12 weeks of continuous administration, no changes in the patient\u2019s lung function were observed.\u00a0The chest X-ray examination was also No abnormalities were seen.\u00a0Nine lung cancer patients were inhaled with different doses of IL-2 liposomes 3 times a day for 20 minutes each time, and no obvious toxic reaction was observed.\u00a0Therefore, the patients were considered to be able to tolerate the inhalation of IL-2 liposomes.<\/p>\n

Bovine serum albumin
\nWith bovine serum albumin (BSA) as a model drug, low-density porous particles (PM) were prepared by the W\/O\/W double-emulsification method.\u00a0The sulfobutyl ether-\u03b2 cyclodextrin is used as a protein stabilizer, sodium hyaluronate is used as a base material, and sucrose ethyl acetate (SAIB) is added to obtain the sustained release effect of protein.\u00a0In vitro studies have shown that due to the high viscosity of SAIB added, BSA can be continuously released from PM for 7 days.\u00a0PM has a small aerodynamic particle size, which can reach the deep lung;\u00a0meanwhile, the density of PM is small, and the geometric particle size is greater than 5 pm.\u00a0Because of the large particle size, macrophages are prevented from phagocytosis, so PM can be used as a protein and peptide drug for the lungs.\u00a0Therefore, PM can be used as a long-acting dosage form for pulmonary administration of protein and peptide drugs.
\nImmune antigen
\nIn the early stage of pulmonary tuberculosis infection, EAST-6 secreted by Mycobacterium tuberculosis is an important antigen for T lymphocyte-mediated immunity.\u00a0Polylactic acid (PLA) particles encapsulating EAST-6 can induce an immune response mediated by lymph node cells in the lungs and mediastinum after being sucked into the lungs.\u00a0The PLA particles have a smooth surface, good roundness, and an average particle size of 1.179\u03bcm.\u00a0D10,\u00a0D50 and D90 are 0.82pm, 1.17\u03bcm and 2.10\u03bcm, respectively.\u00a0The encapsulation rate of EAST-6 is 0.8%.\u00a0Intranasal instillation of the microparticle preparation in mice resulted in a strong immune response in the lungs, indicating that the microparticles have a good application prospect as a carrier of lung infection antigens.<\/p>\n

Plasmid DNA
\nBiological macromolecules, such as biologically active peptides, plasmid DNA and small interfering RNA (siRNA) are usually freeze-dried to prepare nano-sized particles, but they tend to aggregate.\u00a0The spray-drying method is used to prepare PLGA cationic nanospheres as a gene delivery carrier, which can reduce aggregation and improve transfection efficiency.\u00a0Dissolve PLGA and cationic materials in a mixed solvent of acetone\/methanol and add them to stirred water to obtain nanoemulsion.\u00a0Add mannitol and spray dry to obtain mannitol particles containing PLGA nanospheres.\u00a0The particle size is 100~250nm, which is better than the freeze-drying method.\u00a0The obtained PLGA particles have a much smaller particle size.\u00a0Using cationic PLGA\/PEI nanospheres as a carrier of plasmid DNA can avoid damage by nuclease.\u00a0Taking COS-7 cells as a model in vitro, luciferase has obvious expression.\u00a0In vivo experiments in mice showed that cationic PLGA\/PEI nanospheres, as plasmid DNA carriers, interact with serum proteins in vivo and are easily captured by the pulmonary capillary bed, so the luciferase activity is highest in the lungs.\u00a0The luciferase activity of the PLGA\/PEI nanospheres as a carrier is higher than that of the PLGA\/PEI microsphere software, indicating that the particle size affects the efficiency of gene transfection in vivo<\/em>.<\/p>\n","protected":false},"excerpt":{"rendered":"

Pulmonary administration has great advantages as a non-invasive route of administration of protein and peptide drugs. The human respiratory tract has a large surface area, which can avoid the first pass effect of the liver. In addition, the viscosity of the epithelial cell barrier is low, and there is a large amount of potential vasculature, low proteolytic activity and low acidity. Compared with the gastrointestinal tract, there is a thinner mucus layer, so the lungs are suitable for local and systemic administration. However, the mucosa of the respiratory tract is very tight and complex, and it is difficult for macromolecular drugs to penetrate. In fact, a single macromolecule is difficult to cross the epithelial cells, is easily degraded by enzymes in the respiratory tract, and is easily cleared by macrophages or mucociliary hairs, so the bioavailability is very low. For example, the systemic bioavailability of insulin nasal administration is very low, only about 1%, and it is difficult to exert a therapeutic effect. The preparation of protein peptide drugs into nano preparations and then pulmonary administration is an effective method to improve the bioavailability of biotechnology drugs. At present, there are many kinds of protein peptide drugs in the lung inhalation nano-formulations that have proved to be effective. Insulin Insulin liposomes with average particle diameters of 1.91\u03bcm and 2.08\u03bcm were prepared by thin film ultrasonic dispersion method and reverse phase evaporation method.\u00a0After instillation into the rat trachea, the two liposomes had significant blood glucose lowering effects,\u00a0the minimum blood glucose concentration is less than 5%, the time to reach the lowest blood sugar level is about 180 minutes.\u00a0In comparison, intratracheal instillation of the same dose of insulin solution can also significantly reduce blood glucose levels.\u00a0The minimum blood glucose concentration is about 20%, and the time to reach the minimum blood glucose level is about 120 minutes.\u00a0Therefore, liposomes have the effect of promoting the absorption of the islet cord from the lungs.\u00a0The relative bioavailability of insulin liposome pulmonary administration and subcutaneous injection of insulin solution is 37%, while that of insulin solution pulmonary administration is 29%.\u00a0Insulin liposomes and physical suspensions of insulin and blank liposomes have no significant difference in promoting the pulmonary absorption of insulin, enhancing the hypoglycemic effect and prolonging the action time.\u00a0Therefore, the surface activity of liposomal phospholipids and the activation of alveolar surface macrophages are the main factors that promote the absorption of insulin in the lungs. Calcitonin Chitosan-modified nanoparticles have the advantages of bioadhesiveness, slower clearance rate, and longer drug effect time.\u00a0Taking calcitonin as a model drug, PLGA nanoparticles are prepared by the emulsification-solvent diffusion method, and then modified with chitosan to obtain chitosan-modified calcitonin PLGA nanoparticles with a particle size of 650nm and a particle size of about 6.5 \u03bcm after atomization, the effective part deposition rate is 51.3%.\u00a0It has a significant effect on reducing the blood calcium concentration, reducing the blood calcium concentration to 80% of the total calcium content, and the pharmacological effect time can be extended to 24h, which has significant advantages compared with the nanoparticles that are not modified by chitosan. Thymopentin The spray-drying technology is used to prepare lung inhalation microspheres composed of solid lipid nanoparticles loaded with thymopentin.\u00a0The surface of the microspheres is porous, with a particle size of 4.8 \u03bcm, a bulk density as low as 0.48 g\/cm3, and a solid density of 0.71 g\/cm3.\u00a0The microspheres have good inhalation characteristics, the emptying rate is 85.0%, the effective site deposition rate is 61.6%, and they can be effectively distributed into the alveoli.\u00a0Nanoparticles and thymopentin can maintain good stability during the preparation process.\u00a0This new type of microsphere has suitable inhalation characteristics and is a pulmonary drug delivery system with good application prospects. Interleukin Interleukin 2 is a commonly used immunopotentiator for adjuvant treatment of tumors and immunodeficiency diseases.\u00a0It is usually administered by subcutaneous injection, but it is easy to cause swelling at the injection site.\u00a0Aerosolized IL-2 liposomes and blank liposomes with a particle size of 1.1 \u03bcm to immunodeficiency patients and hepatitis patients.\u00a0After 12 weeks of continuous administration, no changes in the patient\u2019s lung function were observed.\u00a0The chest X-ray examination was also No abnormalities were seen.\u00a0Nine lung cancer patients were inhaled with different doses of IL-2 liposomes 3 times a day for 20 minutes each time, and no obvious toxic reaction was observed.\u00a0Therefore, the patients were considered to be able to tolerate the inhalation of IL-2 liposomes. Bovine serum albumin With bovine serum albumin (BSA) as a model drug, low-density porous particles (PM) were prepared by the W\/O\/W double-emulsification method.\u00a0The sulfobutyl ether-\u03b2 cyclodextrin is used as a protein stabilizer, sodium hyaluronate is used as a base material, and sucrose ethyl acetate (SAIB) is added to obtain the sustained release effect of protein.\u00a0In vitro studies have shown that due to the high viscosity of SAIB added, BSA can be continuously released from PM for 7 days.\u00a0PM has a small aerodynamic particle size, which can reach the deep lung;\u00a0meanwhile, the density of PM is small, and the geometric particle size is greater than 5 pm.\u00a0Because of the large particle size, macrophages are prevented from phagocytosis, so PM can be used as a protein and peptide drug for the lungs.\u00a0Therefore, PM can be used as a long-acting dosage form for pulmonary administration of protein and peptide drugs. Immune antigen In the early stage of pulmonary tuberculosis infection, EAST-6 secreted by Mycobacterium tuberculosis is an important antigen for T lymphocyte-mediated immunity.\u00a0Polylactic acid (PLA) particles encapsulating EAST-6 can induce an immune response mediated by lymph node cells in the lungs and mediastinum after being sucked into the lungs.\u00a0The PLA particles have a smooth surface, good roundness, and an average particle size of 1.179\u03bcm.\u00a0D10,\u00a0D50 and D90 are 0.82pm, 1.17\u03bcm and 2.10\u03bcm, respectively.\u00a0The encapsulation rate of EAST-6 is 0.8%.\u00a0Intranasal instillation of the microparticle preparation in mice resulted in a strong immune response in the lungs, indicating that the microparticles have a good application prospect as a carrier of lung infection antigens. Plasmid DNA Biological macromolecules, such as biologically active peptides, plasmid DNA and small interfering RNA (siRNA) are usually freeze-dried to prepare nano-sized particles, but they tend to aggregate.\u00a0The spray-drying method is used to prepare PLGA cationic nanospheres as a gene delivery carrier, which can reduce aggregation and improve transfection efficiency.\u00a0Dissolve PLGA and cationic materials in a mixed solvent of acetone\/methanol and add them to stirred water to obtain nanoemulsion.\u00a0Add mannitol and spray dry to obtain mannitol particles containing PLGA nanospheres.\u00a0The particle size is 100~250nm, which is better than the freeze-drying method.\u00a0The obtained PLGA particles have a much smaller particle size.\u00a0Using cationic PLGA\/PEI nanospheres as a carrier of plasmid DNA can avoid damage by nuclease.\u00a0Taking COS-7 cells as a model in vitro, luciferase has obvious expression.\u00a0In vivo experiments in mice showed that cationic PLGA\/PEI nanospheres, as plasmid DNA carriers, interact with serum proteins in vivo and are easily captured by the pulmonary capillary bed, so the luciferase activity is highest in the lungs.\u00a0The luciferase activity of the PLGA\/PEI nanospheres as a carrier is higher than that of the PLGA\/PEI microsphere software, indicating that the particle size affects the efficiency of gene transfection in vivo.<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[6],"tags":[23],"class_list":["post-749","post","type-post","status-publish","format-standard","hentry","category-application","tag-introduction"],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/www.cd-bioparticles.net\/blog\/wp-json\/wp\/v2\/posts\/749"}],"collection":[{"href":"https:\/\/www.cd-bioparticles.net\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.cd-bioparticles.net\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.cd-bioparticles.net\/blog\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.cd-bioparticles.net\/blog\/wp-json\/wp\/v2\/comments?post=749"}],"version-history":[{"count":2,"href":"https:\/\/www.cd-bioparticles.net\/blog\/wp-json\/wp\/v2\/posts\/749\/revisions"}],"predecessor-version":[{"id":927,"href":"https:\/\/www.cd-bioparticles.net\/blog\/wp-json\/wp\/v2\/posts\/749\/revisions\/927"}],"wp:attachment":[{"href":"https:\/\/www.cd-bioparticles.net\/blog\/wp-json\/wp\/v2\/media?parent=749"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.cd-bioparticles.net\/blog\/wp-json\/wp\/v2\/categories?post=749"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.cd-bioparticles.net\/blog\/wp-json\/wp\/v2\/tags?post=749"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}