{"id":736,"date":"2021-07-26T05:49:48","date_gmt":"2021-07-26T05:49:48","guid":{"rendered":"http:\/\/www.cd-bioparticles.net\/blog\/?p=736"},"modified":"2023-07-18T09:08:47","modified_gmt":"2023-07-18T09:08:47","slug":"lung-inhalation-nano-drug-delivery-system-dosage-form","status":"publish","type":"post","link":"https:\/\/www.cd-bioparticles.net\/blog\/lung-inhalation-nano-drug-delivery-system-dosage-form\/","title":{"rendered":"Lung Inhalation Nano Drug Delivery System Dosage Form"},"content":{"rendered":"

The existing pulmonary inhalation nano drug delivery system dosage forms are mainly divided into two types: liposomes and nanoparticles.<\/p>\n

\"\"
Figure 1. Illustration of respiratory drug delivery, absorption, and clearance.<\/figcaption><\/figure>\n

Liposomes<\/b><\/strong><\/p>\n

Among the various dosage forms for pulmonary administration, liposomes<\/a> have obvious advantages, such as being suitable for encapsulating lipophilic drugs, avoiding local irritation, enhancing curative effects, reducing toxic and side effects, and evenly distributing active drugs in the lungs. Lung-administered liposomes can also be used for gene therapy. Compared with viral vectors, liposomes are simple to prepare, have no damage to normal tissues, and have high safety.<\/p>\n

Liposome pulmonary drug delivery has the following characteristics: 1. The main component of alveoli is lipids, among which phospholipids account for 80% of the lipid components, and liposomes are also composed of phospholipids, which have good compatibility; 2. Drugs The absorption process in the lungs is mainly passive diffusion. The fat solubility of the drug affects the absorption, and the poorly fat-soluble drug encapsulated in liposomes can increase its bioavailability; 3. Reduce the systemic toxicity of anti-tumor drugs; 4. Long-acting slow Interpretation effect.<\/p>\n

The influencing factors of the efficacy and pharmacokinetic characteristics of liposome pulmonary administration include: 1.\u00a0The smaller the liposome particle size, the faster the absorption;\u00a02.\u00a0The higher the cholesterol content, the stronger the liposome rigidity and the slower the drug release.\u00a0The longer the residence time in the lung;\u00a03.\u00a0Saturated phospholipids such as hydrogenated phospholipids are more stable than unsaturated phospholipid liposomes, and have lower membrane permeability;\u00a04.\u00a0Negatively charged lipids accelerate the release of drugs in liposomes, which may be related to opsonins The result of the interaction;\u00a05.\u00a0Disease affects the inner diameter and reactivity of the respiratory tract, which in turn affects drug absorption and distribution.\u00a0As a carrier for pulmonary drug delivery, liposomes still have some problems, such as low drug loading.<\/p>\n

Stability of Liposomes for Pulmonary Delivery<\/p>\n

There is a mucociliary clearance mechanism in the respiratory tract. During tracheal instillation, a considerable part of the drug is cleared, and the drug cannot completely reach the alveoli and enter the systemic circulation. Therefore, liposomal pulmonary administration is mostly used for aerosol inhalation, but aerosol inhalation may affect the stability of drug liposomes. If the liposome leaks rapidly during the aerosolization process, its pulmonary administration is meaningless. The addition of cholesterol helps to improve the stability of liposomes and reduces the leakage rate of hydrophilic drugs from 15%-20% to 8%. The liposomes modified by phytohemagglutinin have good stability and adhesion, significantly increase the affinity of liposomes and cells, and are stable during the process of atomization.<\/p>\n

Liposome Pulmonary Pharmacokinetics<\/p>\n

The tissue distribution after liposome pulmonary administration is related to liposome materials, particle size, surface modification, drug properties and other factors, but almost all reports suggest that liposome pulmonary administration can reach the ideal concentration in the lungs .\u00a0After atomizing and inhaling the liposome of camptothecin dilauroylphosphatidylcholine to mice, the absorption was rapid.\u00a0After 30 minutes, the drug concentration in the lung was 310ng\/g, and it was quickly distributed in the liver (192ng\/g) and brain (61ng\/g), the concentration of the drug in other tissues is very low;\u00a0however, after intramuscular injection of camptothecin dimethyl sulfoxide solution, the absorption of the drug is very slow.\u00a0The drug is mainly distributed in the liver (136ng\/g), and only\u00a0dstribution of trace (24ng\/g) \u00a0in the lung, so the pulmonary administration of camptothecin liposomes has a good application prospect in the treatment of lung, liver, and brain tumors in the future.\u00a0Nebulized gas also has an impact on the pharmacokinetics of liposomes after pulmonary administration.\u00a0Using air containing 5% CO2 to inhale camptothecin liposomes and paclitaxel liposomes in mice is the highest in the lungs.\u00a0The drug concentration is 24 times that of normal air, and the drug concentration in the liver, spleen, kidney, brain and blood is also higher than the latter.<\/p>\n

Pharmacodynamics<\/p>\n

Lung administration of liposomes has obvious advantages in the treatment of local lung diseases (such as fungal infections and tumors).\u00a0Compare the curative effect of amphotericin B liposome and its deoxycholate atomized inhalation on severely immunosuppressed rats with pulmonary aspergillosis.\u00a0The liposome preparations can significantly prolong the survival time of rats at different concentrations and have an effect on alveolar surface activity.\u00a0The substance has no inhibitory effect, and the latter has a significant dose-effect relationship and inhibits alveolar surface active substances.\u00a0Lipopolysaccharide is a component of the cell wall of gram-negative bacteria, which can stimulate phagocytes to produce metabolites and play an important role in acute lung injury.\u00a0Dexamethasone liposomes can prevent acute lung injury caused by lipopolysaccharide.\u00a0Dexamethasone liposome and its free drug (800mg\/kg) were administered to the lungs of rats, and it was found that the efficacy of dexamethasone liposome in preventing lung inflammation and other injuries was significantly better than its free drug.<\/p>\n

Safety Evaluation<\/p>\n

The safety evaluation of liposome pulmonary administration has achieved satisfactory results in animal and human trials.\u00a0Cationic liposomes can induce dose-dependent toxicity and pulmonary inflammation, and multivalent cationic liposomes are more toxic than monovalent cationic liposomes, but neutral and negative ion liposomes have no pulmonary toxicity;\u00a0The release of reactive oxygen intermediates (ROI) caused by multivalent cationic liposomes is the main cause of its pulmonary toxicity.<\/p>\n

Nanoparticles<\/b><\/strong><\/p>\n

Nanoparticles<\/a> have a large specific surface area, an increased dissolution rate, and an increased saturation solubility of the particles.\u00a0They are often used to increase the bioavailability of poorly soluble hydrophobic drugs.\u00a0There are usually two methods for preparing drug-loaded nanoparticles for lung inhalation: 1. Depositing particles from solution (bottom-up), including spray drying, freeze drying, supercritical fluid extraction, microemulsion, electrospray, and solvent replacement Recrystallization;\u00a02.\u00a0Obtained from the crushing of large particles (from top to bottom), including wet grinding and high pressure homogenization.
\nCompared with traditional powder aerosol and liquid pulmonary drug delivery preparations, the advantages of the lung inhalation nano drug delivery system include: 1.\u00a0The surface area of nanoparticles is large, and the bioavailability of insoluble drugs is greatly improved;\u00a02.\u00a0The particles are easier to control than dry powder inhalants.\u00a0Appearance, low-density particles can be obtained, which is more conducive to reaching the deep lungs.\u00a0However, problems such as residual solvents, cytotoxicity, low drug loading and difficulty in large-scale production restrict the commercialization of nano-pulmonary drug delivery systems.<\/p>\n","protected":false},"excerpt":{"rendered":"

The existing pulmonary inhalation nano drug delivery system dosage forms are mainly divided into two types: liposomes and nanoparticles. Liposomes Among the various dosage forms for pulmonary administration, liposomes have obvious advantages, such as being suitable for encapsulating lipophilic drugs, avoiding local irritation, enhancing curative effects, reducing toxic and side effects, and evenly distributing active drugs in the lungs. Lung-administered liposomes can also be used for gene therapy. Compared with viral vectors, liposomes are simple to prepare, have no damage to normal tissues, and have high safety. Liposome pulmonary drug delivery has the following characteristics: 1. The main component of alveoli is lipids, among which phospholipids account for 80% of the lipid components, and liposomes are also composed of phospholipids, which have good compatibility; 2. Drugs The absorption process in the lungs is mainly passive diffusion. The fat solubility of the drug affects the absorption, and the poorly fat-soluble drug encapsulated in liposomes can increase its bioavailability; 3. Reduce the systemic toxicity of anti-tumor drugs; 4. Long-acting slow Interpretation effect. The influencing factors of the efficacy and pharmacokinetic characteristics of liposome pulmonary administration include: 1.\u00a0The smaller the liposome particle size, the faster the absorption;\u00a02.\u00a0The higher the cholesterol content, the stronger the liposome rigidity and the slower the drug release.\u00a0The longer the residence time in the lung;\u00a03.\u00a0Saturated phospholipids such as hydrogenated phospholipids are more stable than unsaturated phospholipid liposomes, and have lower membrane permeability;\u00a04.\u00a0Negatively charged lipids accelerate the release of drugs in liposomes, which may be related to opsonins The result of the interaction;\u00a05.\u00a0Disease affects the inner diameter and reactivity of the respiratory tract, which in turn affects drug absorption and distribution.\u00a0As a carrier for pulmonary drug delivery, liposomes still have some problems, such as low drug loading. Stability of Liposomes for Pulmonary Delivery There is a mucociliary clearance mechanism in the respiratory tract. During tracheal instillation, a considerable part of the drug is cleared, and the drug cannot completely reach the alveoli and enter the systemic circulation. Therefore, liposomal pulmonary administration is mostly used for aerosol inhalation, but aerosol inhalation may affect the stability of drug liposomes. If the liposome leaks rapidly during the aerosolization process, its pulmonary administration is meaningless. The addition of cholesterol helps to improve the stability of liposomes and reduces the leakage rate of hydrophilic drugs from 15%-20% to 8%. The liposomes modified by phytohemagglutinin have good stability and adhesion, significantly increase the affinity of liposomes and cells, and are stable during the process of atomization. Liposome Pulmonary Pharmacokinetics The tissue distribution after liposome pulmonary administration is related to liposome materials, particle size, surface modification, drug properties and other factors, but almost all reports suggest that liposome pulmonary administration can reach the ideal concentration in the lungs .\u00a0After atomizing and inhaling the liposome of camptothecin dilauroylphosphatidylcholine to mice, the absorption was rapid.\u00a0After 30 minutes, the drug concentration in the lung was 310ng\/g, and it was quickly distributed in the liver (192ng\/g) and brain (61ng\/g), the concentration of the drug in other tissues is very low;\u00a0however, after intramuscular injection of camptothecin dimethyl sulfoxide solution, the absorption of the drug is very slow.\u00a0The drug is mainly distributed in the liver (136ng\/g), and only\u00a0dstribution of trace (24ng\/g) \u00a0in the lung, so the pulmonary administration of camptothecin liposomes has a good application prospect in the treatment of lung, liver, and brain tumors in the future.\u00a0Nebulized gas also has an impact on the pharmacokinetics of liposomes after pulmonary administration.\u00a0Using air containing 5% CO2 to inhale camptothecin liposomes and paclitaxel liposomes in mice is the highest in the lungs.\u00a0The drug concentration is 24 times that of normal air, and the drug concentration in the liver, spleen, kidney, brain and blood is also higher than the latter. Pharmacodynamics Lung administration of liposomes has obvious advantages in the treatment of local lung diseases (such as fungal infections and tumors).\u00a0Compare the curative effect of amphotericin B liposome and its deoxycholate atomized inhalation on severely immunosuppressed rats with pulmonary aspergillosis.\u00a0The liposome preparations can significantly prolong the survival time of rats at different concentrations and have an effect on alveolar surface activity.\u00a0The substance has no inhibitory effect, and the latter has a significant dose-effect relationship and inhibits alveolar surface active substances.\u00a0Lipopolysaccharide is a component of the cell wall of gram-negative bacteria, which can stimulate phagocytes to produce metabolites and play an important role in acute lung injury.\u00a0Dexamethasone liposomes can prevent acute lung injury caused by lipopolysaccharide.\u00a0Dexamethasone liposome and its free drug (800mg\/kg) were administered to the lungs of rats, and it was found that the efficacy of dexamethasone liposome in preventing lung inflammation and other injuries was significantly better than its free drug. Safety Evaluation The safety evaluation of liposome pulmonary administration has achieved satisfactory results in animal and human trials.\u00a0Cationic liposomes can induce dose-dependent toxicity and pulmonary inflammation, and multivalent cationic liposomes are more toxic than monovalent cationic liposomes, but neutral and negative ion liposomes have no pulmonary toxicity;\u00a0The release of reactive oxygen intermediates (ROI) caused by multivalent cationic liposomes is the main cause of its pulmonary toxicity. Nanoparticles Nanoparticles have a large specific surface area, an increased dissolution rate, and an increased saturation solubility of the particles.\u00a0They are often used to increase the bioavailability of poorly soluble hydrophobic drugs.\u00a0There are usually two methods for preparing drug-loaded nanoparticles for lung inhalation: 1. Depositing particles from solution (bottom-up), including spray drying, freeze drying, supercritical fluid extraction, microemulsion, electrospray, and solvent replacement Recrystallization;\u00a02.\u00a0Obtained from the crushing of large particles (from top to bottom), including wet grinding and high pressure homogenization. Compared with traditional powder aerosol and liquid pulmonary drug delivery preparations, the advantages of the lung inhalation nano drug delivery system include: 1.\u00a0The surface area of nanoparticles is large, and the bioavailability of insoluble drugs is greatly improved;\u00a02.\u00a0The particles are easier to control than dry powder inhalants.\u00a0Appearance, low-density particles can be obtained, which is more conducive to reaching the deep lungs.\u00a0However, problems such as residual solvents, cytotoxicity, low drug loading and difficulty in large-scale production restrict the commercialization of nano-pulmonary drug delivery systems.<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[16],"tags":[23],"class_list":["post-736","post","type-post","status-publish","format-standard","hentry","category-delivery-method","tag-introduction"],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/www.cd-bioparticles.net\/blog\/wp-json\/wp\/v2\/posts\/736"}],"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=736"}],"version-history":[{"count":1,"href":"https:\/\/www.cd-bioparticles.net\/blog\/wp-json\/wp\/v2\/posts\/736\/revisions"}],"predecessor-version":[{"id":738,"href":"https:\/\/www.cd-bioparticles.net\/blog\/wp-json\/wp\/v2\/posts\/736\/revisions\/738"}],"wp:attachment":[{"href":"https:\/\/www.cd-bioparticles.net\/blog\/wp-json\/wp\/v2\/media?parent=736"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.cd-bioparticles.net\/blog\/wp-json\/wp\/v2\/categories?post=736"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.cd-bioparticles.net\/blog\/wp-json\/wp\/v2\/tags?post=736"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}