Pdf chemotherapeutic drug targeting to lungs by way of. Jun 18, 2015 amphiphilic polyn isopropylacrylamideblockpoly. After intravenous injection they normally distribute into the organs of the reticuloendothelial system liver, spleen, lungs, bone marrow. Targeted drug delivery systems for lung macrophages. Different system used to target lungs methods used to identify the deposition of inhaled products ex. Targeting redox heterogeneity to counteract drug tolerance. Since there is high concentration on the patch and low concentration in the blood, the drug will keep diffusing into the blood for a long period of time, maintaining the constant concentration of drug in the blood flow. In case of brochodialating drugs, this is advantageous as drug will deliver directly to region where its action is required so that the drug effect will be faster and low dose of drug can be administered through this delivery system and. Nonetheless, there have been situations when developers have deemed it faster and more costeffective to reach a phase i clinical study with a nebulized dosage form, even when the final product is expected to be. The pulmonary route of drug delivery has been targeted for both the systemic. However, their body distribution can be altered by coating with surfactants or with physiological components such as serum complement factors. The dual drug delivery system described herein aims to overcome these two challenges by selectively targeting the lung to deliver anticancer drugs and inhibit the formation of metastases. Targeting redox heterogeneity to counteract drug tolerance in.
The delivery device plays a major role in the efficiency of pulmonary delivery, and great strides have been. Nov, 2019 phagosomal ph and redox heterogeneity in mycobacterium tuberculosis mtb can promote tolerance of the bacterium to antibiotics. Targeted drug delivery, sometimes called smart drug delivery, is a method of delivering medication to a patient in a manner that increases the concentration of the medication in some parts of the body relative to others. Antiangiogenesis therapies for the treatment of cancers hold the promise of high efficacy and low toxicity. Pulmonary drug delivery for remote targeting has received less attention than local delivery to treat lung. In contrast to oral delivery, where a drug can be heavily metabolized and altered by the enzymes of the gut and liver, the lungs have only a small fraction of the drugmetabolizing and efflux transporter activity of the gut and liver 35. The surface morphology was found to be shriveled to nearly spherical, with an average size of 6. Adaptive nebulizers were designed for the administration of drugs at a specific time during inspiration, depending on the intended target drugtargeting nebulization. As a result of release, the retention decreases gradually to 5% after 30 s, the point where 95% of the area under the dye curve is reached, the first. On systemic administration, long circulating immunoliposomes are able to recognize and bind to target cells with greater specificity 15.
Components for drug targeting target specific organ or a cell or group of cells, which in chronic or acute condition need treatment. The obtained plga nps have excellent cytocompatibility. Since the drug is delivered directly to its required site, only a small quantity is needed for an adequate therapeutic response, and consequently there. Effect of drugtargeting nebulization on lung delivery. Alveolar macrophages, drug delivery systems, ligands, macrophages receptors, mannose receptors, targeting. Aerosol drug delivery to the lungs generally facilitates uptake to the systemic circulation. Researchers in the department of chemical and biological engineering, princeton university and in the department of pharmaceutics, rutgers university have developed a targeted lungspecific delivery system which employs both passive and active targeting to intravenously deliver anticancer drugs to tumor cells as well as to reduce the. The physiology of lungs makes it possible to target them via two different routes through the circulation and through the respiratory. For example, ephidrine for nasal decongestion, beta2 agonists for bronchodilatation, and inhaled steroids to suppress the inflammation seen in asthmatic airways. The rate of drug deposition in the lungs during the inhalational technique. Although our understanding of these diseases has improved significantly over the past decades, diagnostic and therapeutic options for treating lung diseases, such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and lung cancer, remain limited.
The most desirable approach is that a drug development program can be started using the dosage form that is intended to be marketed. If you dont treat them, they can get worse and lead to infections. Targeted drug delivery via caveolaeassociated protein pv1. Sep 30, 2004 the lungs are even more permeable to small molecules than the gastrointestinal gi tract. New drug delivery systems such as liposomes, nanospheres and microspheres can result in higher concentrations of amb in the liver and spleen, but lower concentrations in kidney and lungs, so decreasing its toxicity. Dec 20, 2014 combination targeting these targeting systems are equipped with carriers, polymers and homing devices of molecular specificity that could provide a direct approach to target site.
The respiratory system is becoming a more popular drug delivery avenue to combat various diseases. Targeted drug delivery for the lungs technion technology. Recent advances in aerosolised drug delivery sciencedirect. Targeted delivery of inhalation medicine using magnetic particles targeted delivery of drugs in the respiratory pathway can be the key for effective treatment of various lung diseases e. Us20190038574a1 nanoparticle targeted drug delivery to the. The drug carrying capacity, release rate and deposition of liposome in the lungs is dependent upon lipid composition, size, and charge and druglipid ratio. Pulmonary drug delivery wiley online books wiley online library. Pulmonary drug delivery provides a noninvasive, alternative method to subcutaneous injection, and also intravenous injection. Although many nanomaterials including graphene oxide go and molybdenum disulfide mos2 have been. Pdf targeting drug delivery to the lungs by inhalation. What are the side effects of targeted therapy for non.
Inhalation drug products have a multitude of benefits when delivering treatment to the lungs, including a faster onset because of direct delivery to the area requiring therapeutic treatment and reduced occurrence of adverse effects. Testisderived rat sertoli cells were preloaded with chitosan nanoparticles coupled with or without the drug curcumin, prelabeled with a fluorescent cell. Pulmonary drug delivery is a developing technology in which medication is inhaled through the lungs and enters the bloodstream through the alveolar epithelium. Targeting the upper bronchial region is not possible. The lungs as a portal of entry for systemic drug delivery.
Intratracheal administration is commonly used as a first approach in lung drug delivery in vivo. Given the passive lung targeting ability, low immunogenicity and tissue repairpromoting of msc and the extensive preclinical and clinical research basis for application of msc, msc may also be useful in lung targeted drug delivery for chronic pneumonia treatment and other lung related diseases, in addition to being used as a drug carrier for. A targeting efficiency of 25% is the maximum efficiency achievable for that region. Respiration triggered magnetic drug targeting in the lungs. Technology targeted dual drug delivery system for nonsmall. If there is a lack ofclinical response to an aerosolized drug, it is important to question whether the drug has failed or whether delivery to the site of action is inadequate. Lungs give giant extent about 100m2 and high biological process that chopchop distribute the molecules. There has been significant progress on the understanding of drug therapy via inhalation products. Request pdf respiration triggered magnetic drug targeting in the lungs lung cancer kills per year 1. Portrazza necitumumab cancer often finds a way around targeted therapies and they stop working see drug resistance information on page 16. Selective and effective localization of the pharmacologicallyactive moiety at prei. Locoregional cancer treatment with magnetic drug targeting. Respiratory diseases are an increasing burden for the ageing population. In this respect, the large surface area of approximately.
Based on this approach, drug conjugates can be prepared with fortified activity profile against the viral replication. The critical micelle concentration increased from 1. Molybdenum disulfidegraphene oxide nanocomposites show. To deliver therapeutic agents by inhalation to the lower respiratory tract, inhaled drug particles must have appropriate aerodynamic characteristics. Airway geometry, humidity, mucociliary clearance and alveolar macrophages play a vital role in maintaining the sterility of the lung and consequently are barriers. Pulmonary drug delivery an overview sciencedirect topics. Technology targeted dual drug delivery system for non. Special areas of interest include the design and characterization of carrier systems for both vitro and in vivo applications. Full text chemotherapeutic drug targeting to lungs by. On systemic administration, long circulating immunoliposomes are able to recognize and bind to. Most drugs targeted to the respiratory tract are used for their local action.
Since the drug is delivered directly to its required site, only a small quantity is needed for an adequate therapeutic response, and consequently there is. Targeted drug delivery of antitumour malignant neoplasm metastatic tumor drug on tumor web site in lungs improves the therapeutic impact as a result of it decreases the general exposure of drug. What is drug targeting the therapeutic response of a drug depends upon the interaction of drug molecules with cell on cell membrane related biological events at receptor sites in concentration dependent manner. Drug targeting is defined as the ability of a drug molecule to accumulate in the target organ or tissue selectively such that the concentration of the drug at the disease site is high, while its concentration in nontarget organs and tissues is low, preferably, below certain minimal level so as to prevent any toxic effect. A medlineindexed journal dedicated to all aspects of drug delivery and targeting for molecular and macromolecular drugs. Us10272053b2 nanoparticle targeted drug delivery to the. Pharmatutorart1700 introduction the delivery of the drug through the respiratory tract is called pulmonary drug delivery. The lungs are even more permeable to small molecules than the gastrointestinal gi tract. Carbopol microspheres of methotrexate mxtcm, a drug used in the treatment of lung cancer, were prepared using a buchi b90 nano spray dryer. Drug concentrations are initially less than the dye concentrations, indicating lung uptake, and later are greater than dye concentrations, indicating release of the drug from the lungs. Amphotericin b formulations and drug targeting torrado. The high efficiency of lung targeting of mscs was validated in different animals, and this system efficiently inhibited primary lung tumor growth with lower dose of anticancer drug. Novel drying technology of microsphere and its evaluation for.
Another drug, portrazza works by targeting egfr and is approved in combination with chemotherapy only in squamous cell lung cancer. The delivery device plays a major role in the efficiency of pulmonary. In order to get both local and systemic effects, lungs as the main part of the respiratory system offer an interesting route to noninvasive drug administration. The pharmacokinetics, toxicity and activity are clearly dependent on the type of amphotericin b formulation. Lung macrophages present an effective role in innate and immune response through specific and nonspecific mechanisms, namely phagocytosis, antigen processing and presentation through major histocompatibility complex. The design of the human lung affords unique targeting options.
Delivery of a larger fraction of the drug to the desired diseased site, reducing the drugs exposure to normal tissues can be achieved by site specific targeting. Inflammationtargeting polymeric nanoparticles deliver. One approach, developed in the past to address this problem, is the i. Selective targeting plus optimal biocompatibility is still a big challenge in nanomedicine. Cancer metastasis is the main cause for the high mortality in breast cancer patients. Drug therapy via inhalation route is at the cutting edge of modern drug delivery research. Fundamentals of pulmonary drug delivery respiratory medicine. Tagrisso is a different egfr therapy that targets a specific change. Responsive wormlike micelles with sequential metastasis targeting inhibit lung metastasis of breast cancer. However, there are still problems associated with their formulation design, including the interaction between the active pharmaceutical ingredients apis, excipients and devices. Novel drying technology of microsphere and its evaluation. Most liposomal carrierdrug systems have been investigated in aqueous systems using nebulisation. Nanoparticle targeted drug delivery to the lungs using extratesticular sertoli cells download pdf info publication number us20190038574a1.
Effect of drug targeting nebulization on lung deposition. Chemotherapeutic drug targeting to lungs by way of. Nanoparticles for drug delivery to the lungs jean c. Edwards2 1harvard school of engineering and applied sciences, 40 oxford street, esl 406, cambridge, ma 028, usa 2harvard school of engineering and applied sciences, 322 pierce hall, 29 oxford street, cambridge, ma 028, usa the lungs are an attractive route for noninvasive drug. Pv1 antibodies homed to both healthy and fibrotic lungs, we next sought to determine whether this tissue targeting could be utilized to shuttle drugs to fibrotic lungs.
Drug targeting to lungs by way of microspheres springerlink. Chemotherapeutic drug targeting to lungs by way of microspheres after intravenous administration article pdf available in drug design, development and therapy volume 12. Glome found to release the drug to a maximum extent in the target tissue, lungs. Content anatomy of lungs receptors present in lungs advantages and disadvantages optimal site of deposition for treatment of lung diseases barriers to macromolecule to absorbed mechanisms of particle deposition in the airways. Pv1 antibodies homed to both healthy and fibrotic lungs, we next sought to determine whether this tissue targeting could be utilized to. In vivo phage display was used to identify peptides specifically targeting tumor blood vessels. Us20190038574a1 nanoparticle targeted drug delivery to. A new method to target delivery of very small volumes of drugs into the lungs may one day provide much more effective treatment for a variety of lung diseases, according to a new study the approach uses microliters of liquid that contain a drug instilled into the lung and distributed as a thin film in the predetermined region of the lung airway, where it is absorbed locally. Medical nanoparticles for next generation drug delivery to. This means of delivery is largely founded on nanomedicine, which plans to employ nanoparticlemediated drug delivery in order to combat the downfalls of. Key targeting approaches for pharmaceutical drug delivery. Drug targeting nebulization delivered a large amount of drug into the peripheral part of the lung independent of the modality outertoinner deposition ratio of 1.
A method of delivering a compound of interest to the lungs of a subject by the intravenous injection of sertoli cells loaded with a plurality of chitosan nanoparticles coupled with the compound of interest is provided. It is the most fatal cancer type as far as men are concerned and. Full text chemotherapeutic drug targeting to lungs by way. Peptidemediated targeting to tumor blood vessels of lung. Dual targeting this classical approach of drug targeting employs carrier molecules, which have their own intrinsic antiviral effect thus synergies the antiviral effect of the loaded active drug. The selected drug was indicated for multiresistant tuberculosis, and administration through inhalation allows both local delivery of the drug to the lungs and systemic therapy. Treatment of lung cancer by targeted drug delivery systems. The peptide sp552 recognized tumor neovasculature but not normal blood vessels in severe combined immunodeficiency mice bearing human tumors. Targeting inhaled therapy beyond the lungs fulltext respiration. Different system used to target lungs methods used to identify the deposition of inhaled products ex vivo models of drug absorption across the. Moreover, these technologies can be applied to diagnose fibrosis progression in different diseases and tumor. Targeting the lower bronchial region is also rather ineffective. Targeting drug delivery to the lungs by inhalation.
In this study, mscs were used as lung targeted delivery vehicles by loading nanoparticles that carrying anticancer drug. Targeted drug delivery systems, lung cancer, nanocarrier introdution lung cancer is the most chronic disease among the all other airways and lung disease and one. In case of brochodialating drugs, this is advantageous as drug will deliver directly to region where its action is required so that the drug effect will be faster and low dose of drug can be administered through this delivery system and so the side effects. The specific delivery of chemotherapeutic agents to their desired targets with a minimum of systemic side effects is an important, ongoing challenge of chemotherapy. View enhanced pdf access article on wiley online library html view download pdf for offline viewing. Proceedings of the american thoracic society ats journals. Chemotherapeutic drug targeting to lungs by way of microspheres after intravenous administration sibghatullah sangi,1 nagaraja sreeharsha,2 abdulhakim bawadekji,3 mouhanad al ali4 1department of clinical pharmacy, faculty of pharmacy, northern border university, rafha, saudi arabia. Given the passive lung targeting ability, low immunogenicity and tissue repairpromoting of msc and the extensive preclinical and clinical research basis for application of msc, msc may also be useful in lungtargeted drug delivery for chronic pneumonia treatment and other lung related diseases, in addition to being used as a drug carrier for. Passive targeting of thermosensitive diblock copolymer. Yet, existing inhalation devices lack the ability to target a specific pulmonary region e. Lung anatomy and physiology and their implications for pulmonary drug. It has been difficult to develop more effective nebulizers for the improved delivery of drugs directly to the lungs.