Nanotechnology in Other Chest Diseases

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Nanotechnology In Other Chest Diseases BY Heba Hamed Eltrawy Ass. Lectural of chest diseases Faculty of medicine for Girls ALAzhar University

AIM OF USE OF NANOTECHNOLOGY IN TREARTMENT:

AIM OF USE OF NANOTECHNOLOGY IN TREARTMENT

INTRODUCTION:

INTRODUCTION Nanoparticles (NPs) are solid colloidal drug delivery systems that are submicron in size (1 to 1000 µm) and used to deliver drugs, genes or vaccines to specific tissue or cells by targeted delivery or systemic route. Besides systemic delivery, they also offer other non-invasive routes of administration, such as the nasal route.

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The nanoparticulate systems provide novel systems for selective delivery of both low and high molecular weight drugs to nasal epithelia and lungs. Many low molecular weight, non-polar drugs (<250D) in solution form are able to effortlessly infiltrate the nasal or lung epithelium for sub-epithelial delivery. The proposed mechanism of absorption of these low molecular weight drugs is via aqueous channels.

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Molecules higher than 250D, have trouble in absorption in the airway, similar to that in gastrointestinal-tract. The absorption through lung epithelium also requires bypassing through excessive mucus layer especially in obstructive airway disease conditions.

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Absorption enhancers are being used to enhance absorption of drug across the nasal and lung epithelia. In addition, coating of NPs with mucolytic agents or compounds to open epithelial tight junctions and increase membrane fluidity may help in sub-epithelial delivery.

Therapeutic Application of Nanoparticulate Gene and Drug Delivery in Pulmonary Diseases :

Therapeutic Application of Nanoparticulate Gene and Drug Delivery in Pulmonary Diseases

NANOTECHNOLOGY Application in Pneumonia and Chest infections :

NANOTECHNOLOGY Application in Pneumonia and Chest infections

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New Test Diagnoses Pneumonia in 10 Minutes By Deborah Mitchell 2010-12-20 04:24 A new test allows clinicians to identify a common type of pneumonia within 10 minutes rather than the days it can now take to make a diagnosis. Researchers at the University of Georgia developed the test with the help of nanotechnology.

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Krause and his colleagues expanded upon existing technology called surface-enhanced Raman spectroscopy by using nanorod arrays, which can detect the bacteria responsible for pneumonia in throat swab specimens Spectroscopy was originally the study of the interaction between radiation and matter as a function of wavelength (''λ''). In fact, historically, spectroscopy referred to the use of visible light dispersed according to its wavelength, e.g. by a prism.

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What is Raman Spectroscopy? Raman spectroscopy is an analytical tool concerned with radiation scattering from a sample such that the structure, properties and environment can be studied based on vibrational transitions within the material. This technique is based on the Raman effect (inelastic scattering of light) discovered in 1928 by Indian Physicist Chandrashekhara Venkata Raman.

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Raman found that sunlight interacted with molecules to produce a characteristic pattern when a small fraction of the incident radiation is scattered by the molecule and that it differed in wavelength from that of the incident beam. It was also noted that the shifts in the wavelength depended on the chemical structure of the molecules responsible for the scattering.

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Mechanism of Raman scattering The different vibrational modes associated with the groups of the structure will give different Raman shifts that can then be plotted to give a fingerprint of the material of interest and this is what we know as the Raman spectrum.

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' Nanotechnology' May Simplify Antibiotic Treatment A spray of antibiotics encapsulated in microscopic antimicrobial silver carbene complexes (SCCs) proved highly successful at just half the dosage of conventionally inhaled antibiotics in tests on mice infected with Pseudomona aeroginosa , a common bacteria that causes a pneumonia-like respiratory illness in people. "During a 72-hour period, all of the infected control mice died, whereas all of the mice that received just two doses of SCC22-loaded nanoparticles spaced 24 hours apart survived,“ investigator Dr. Carolyn L. Cannon, of the Washington University School of Medicine, said in a news release issued by the American Thoracic Society.

Nanotechnology vaccines against some micro organisms causing pneumonia:

Nanotechnology vaccines against some micro organisms causing pneumonia

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Scientists in the US have developed a novel vaccination method that uses tiny gold particles to mimic a virus and carry specific proteins to the body's specialist immune cells. The technique differs from the traditional approach of using dead or inactive viruses as a vaccine and was demonstrated in the lab using a specific protein that sits on the surface of the respiratory syncytial virus (RSV).

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RSV is the leading viral cause of peumonia and lower RTI, causing several hundred thousand deaths and an estimated 65 million infections a year, mainly in children and the elderly. The deterimental effects of RSV come, in part, from a specific protein, called the F protein, which coats the surface of the virus. The protein enables the virus to enter into the cytoplasm of cells and also causes cells to stick together, making the virus harder to eliminate.

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The body's natural defence to RSV is therefore directed at the F protein; however, up until now, researchers have had difficulty creating a vaccine that delivers the F protein to the specialised immune cells in the body. If successful, the F protein could trigger an immune response which the body could 'remember' if a subject became infected with the real virus.

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In this study the researchers created exceptionally small gold nanorods, just 21 nanometres wide and 57 nanometres long, which were almost exactly the same shape and size as the virus itself. The gold nanorods were successfully coated with the RSV F proteins and were bonded strongly thanks to the unique physical and chemical properties of the nanorods themselves.

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The researchers then tested the ability of the gold nanorods to deliver the F protein to specific immune cells, known as dendritic cells, which were taken from adult blood samples. Dendritic cells function as processing cells in the immune system, taking the important information from a virus, such as the F protein, and presenting it to cells that can perform an action against them—the T cells are just one example of a cell that can take action. Once the F protein-coated nanorods were added to a sample of dendritic cells, the researchers analysed the proliferation of T cells as a proxy for an immune response

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They found that the protein-coated nanorods caused the T cells to proliferate significantly more compared to non-coated nanorods and just the F protein alone. Not only did this prove that the coated- nanorods were capable of mimicking the virus and stimulating an immune response, it also showed that they were not toxic to human cells, offering significant safety advantages and increasing their potential as a real-life human vaccine. Lead author of the study, Professor James Crowe, said: "A vaccine for RSV, which is the major cause of viral pneumonia in children, is sorely needed.

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This platform could be used to develop experimental vaccines for virtually any virus, and in fact other larger microbes such as bacteria and fungi .

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2. Cystic Fibrosis (CF) CF is a consequence of mutation(s) in the CFTR gene, resulting in imbalanced ion and water movement in the airway epithelium. This leads to accumulation of mucus, bacterial infection and chronic inflammation in the lungs . The most common mutation, ΔF508-CFTR, is a temperature-sensitive, trafficking mutant with reduced chloride transport and exaggerated immune response .

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Since CF is a monogenic disease, gene therapy of CF is an extremely promising avenue that aims to reverse this disease by introducing exogeneous CFTR gene in the airway epithelial cells via the pulmonary route. A number of CF clinical trials involving nanoparticulate gene transfer have been conducted using a variety of cationic lipids, either by aerosolized delivery or direct instillation in the nose .

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Although no toxic side effects could be observed, the trials resulted in little or no functional correction of CF. Some encouraging results were obtained upon nebulized delivery of the lipid-gene complex directly into the lungs, whereby about 25 % of restoration of chloride conductance towards normal values were demonstrated

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A critical factor responsible for the poor CF nanoparticulate gene transfer is the large size (several hundred nanometers) of the vector-DNA complex, which precludes their entry into the nucleus of the virtually non-dividing airway epithelial cells. In order to circumvent this problem, Copernicus Therapeutics have recently developed ultra small nanoparticulate DNA complexes (size less than 25 nanometers), which can passively enter the nucleus through the NPC and transfect post-mitotic cells

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Copernicus showed that the methods used to produce DNA nanoparticles were also very effective when applied to siRNA. Both DNA nanoparticles as well as nanoparticles made with siRNA are highly resistant to degradative processes that would destroy the therapeutic benefit of the nanoparticles. These findings are significant because siRNAs can be designed to block the expression of specific genes and have the potential to treat numerous human diseases, including viral infections . A 2006 Nobel Prize was awarded to the scientists that discovered siRNA.

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Recently, a clinical trial was conducted using a single CFTR plasmid molecule compacted with PEG substituted polylysine (overall size less than 25 nanometers) by intranasal administration . Some evidence of functional correction of CF could be observed in 7 out of 12 patients with no signs of toxic side effects.

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In addition to gene therapy, other therapeutic applications of nano-delivery in CF include selective and sustained delivery of small molecules. As an example, we recently proposed the therapeutic application of extremely potent, stable, reversible, and selective proteasome inhibitor drug, bortezomib (Velcade or PS-341) for treatment of conformational and inflammatory pathophysiology in CF .

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The recent approval of bortezomib as a drug for refractory multiple myeloma has initiated the examination of protein catabolism for potential therapeutic intervention in various conformational protein disorders. Proteasome modulators were also recently shown to have dual therapeutic importance in pharmaco -gene therapy of CF airway . A major concern in considering the proteasome as a therapeutic target is the theoretical risk that multiple processes may be affected by proteasome inhibitors.

Alpha-1-antitrypsin (AAT) deficiency (ATD), COPD, Emphysema :

Alpha-1-antitrypsin (AAT) deficiency (ATD), COPD, Emphysema

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Therapeutic applications of nano-delivery in airway diseases involve targeted delivery of DNA, siRNA, drugs or peptides to hematopoietic progenitor cells and pulmonary epithelium to control chronic pathophysiology of obstructive and conformational disorders. The major challenges of nano-delivery involve physiological barriers like mucus and alveolar fluid for intranasal and reticuloendothelial (RES) system for systemic delivery.

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ATD is another monogenic lung disease amenable to treatment with the synthetic vectors and is characterized by low levels of AAT, the principal antiprotease present in the human plasma, leading to enhanced susceptibility of the lungs to COPD and emphysema . Cationic lipids, with their ability to transfect the lung parenchyma, can be used for localized delivery of the AAT gene in the lung. Alternately, the liver can also be transduced to produce AAT which can reach the lung through systemic circulation

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A single clinical trial was conducted with intranasal delivery of the AAT gene in the form of a lipoplex. Although only transient enhancement of the AAT levels was observed, that too peaking to only about one third of the normal level, some anti-inflammatory effect was observed as evidenced by the decreased IL-8 levels in the nasal fluid .

NANO- TECHNOLGY :

NANO- TECHNOLGY In Bronchial Asthma

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Nanotechnology opens a wide door on future medicine and it is hoped to solve many unsolved medical problems . Development of biodegradable nanoparticles encouraged research on respiratory diseases .

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Itraconazol nanoparticles given by inhalation effectively controlled growth of Aspergillus than oral route in allergic aspergellosis

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Chitosan ( a cationic natural biopolymer produced by the alkaline N - deacetylation of chitin) nanoparticles are used as Gene vector with efficient transfer of IF- ϒ cloned DNA to respiratory epith . with marked attenuation of allergic inflammation in mice. SiRNA (short interfering) against specific viral antigens carried by chitosan nanoparticles and given intra-nasally protected against RSV.

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Theophylline given coated on chitosan nanoparticles intra nasally has effective broncho dilatation and anti inflammatory effect with low serum levels.

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Science, specially medicine, is continuously changing with new ideas, thoughts and applications every day So, we hope in future that some of such ideas or applications aid in solving the problem of bronchial asthma

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Nanotechnology Approach for Treatment of Pulmonary (Lung) Fibrosis

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Idiopathic Pulmonary Fibrosis (IPF), the spontaneous development of scar tissue within the lungs, is a progressive fibrotic disease which impairs the lung’s ability to get oxygen. To date, its pathogenesis remains elusive. Pirfenidon e , is an orally active, small molecule drug that was licensed for the treatment of adults with mild to moderate IPF in the EU in 2011 and has been available in Japan since 2008. It has been granted Orphan Drug and Fast Track designation by the FDA in the USA . It inhibits the synthesis of TGF-beta, a chemical mediator that plays a key role in fibrosis, and inhibits the synthesis of TNF-alpha, a cytokine with an active role in inflammation .

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Pirfenidone nanoparticles has well-established antifibrotic and anti-inflammatory properties in various in vitro systems and animal models of fibrosis . A number of cell-based studies have shown that pirfenidone reduces fibroblast proliferation, inhibits TGF-β stimulated collagen production and reduces the production of fibrogenic mediators such as TGF-β.Pirfenidone has also been shown to reduce production of inflammatory mediators such as TNF-α and IL-1β in both cultured cells and isolated human peripheral blood mononuclear cells . These activities are consistent with the broader antifibrotic and anti-inflammatory activities observed in animal models of fibrosis

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Researchers have designed novel delivery mechanisms for PGE2- and nucleic acid-containing nanoparticles for treatment of IPF. These researchers have demonstrated that in comparison to conventional treatments, this delivery system enhanced therapeutic efficacy, restricted lung tissue damage and completely prevented animal mortality.

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In addition, genetic analysis revealed that the inhalation of liposomal PGE2 prevented disturbances in expression of genes linked to development of IPF, inflammation and fibrotic injury

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Though such results are not sufficient for drawing much clinical attention, a better future of the synthetic carriers against this disease can be expected, with modifications similar to that required for CF gene therapy. The similar nano-based gene and drug delivery systems are also studied for therapeutic application in other airways diseases like asthma THANK YOU