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nano drugs in cystic fibrosis

Barbara Porsio, Emanuela Fabiola Craparo, Nicolò Mauro, Gaetano Giammona, Gennara Cavallaro
Here, mucus-penetrating nanoparticles (NPs) for pulmonary administration of ivacaftor in patients with cystic fibrosis (CF) were produced with the dual aim of enhancing ivacaftor delivery to the airway epithelial cells, by rapid diffusion through the mucus barrier, and at the same time, promoting ivacaftor lung cellular uptake. Pegylated and Tat-decorated fluorescent nanoparticles (FNPs) were produced by nanoprecipitation, starting from two synthetic copolymers, and showed nanometric sizes (∼70 nm), a slightly negative ζ potential, and high cytocompatibility toward human bronchial epithelium cells...
January 10, 2018: ACS Applied Materials & Interfaces
Barbara Porsio, Maria Grazia Cusimano, Domenico Schillaci, Emanuela Fabiola Craparo, Gaetano Giammona, Gennara Cavallaro
Here, nano into micro formulations (NiMs) of tobramycin for the treatment of Pseudomonas aeruginosa airway infections in cystic fibrosis (CF) are described. NiMs were produced by spray drying a solution containing polymers or sugars and a nanometric polyanion-tobramcyin complex (PTC), able to achieve a prolonged antibiotic release. NiMs properties were compared to TOBIPodhaler(Novartis), the only one commercially available dry powder inhalatory formulation based on porous microparticles. Produced NiMs showed adequate characteristics for pulmonary administration, as spherical shape, micrometric size, and high cytocompatibility toward human bronchial epithelial cells...
December 11, 2017: Biomacromolecules
Nazende Günday Türeli, Afra Torge, Jenny Juntke, Bianca C Schwarz, Nicole Schneider-Daum, Akif Emre Türeli, Claus-Michael Lehr, Marc Schneider
Current pulmonary treatments against Pseudomonasaeruginosa infections in cystic fibrosis (CF) lung suffer from deactivation of the drug and immobilization in thick and viscous biofilm/mucus blend, along with the general antibiotic resistance. Administration of nanoparticles (NPs) with high antibiotic load capable of penetrating the tight mesh of biofilm/mucus can be an advent to overcome the treatment bottlenecks. Biodegradable and biocompatible polymer nanoparticles efficiently loaded with ciprofloxacin complex offer a solution for emerging treatment strategies...
May 2, 2017: European Journal of Pharmaceutics and Biopharmaceutics
Ayca Yildiz-Pekoz, Yildiz Ozsoy
Heparin is well known for its anticoagulant and anti-inflammatory properties. Inhaled heparin regimens are increasingly being used to manage lung disease. It has been used to treat cystic fibrosis, thromboembolism, and pulmonary fibrosis, as well as bronchial asthma and asthma-induced airway hypersensitivity. Several preclinical studies attained some useful effects of heparin-administered, parenterally and through inhalation, treatment of lung disease. Besides, recent clinical trials suggest that inhaled heparin for lung diseases is beneficial and safe, but such data remain to be limited...
June 2017: Journal of Aerosol Medicine and Pulmonary Drug Delivery
Emanuela F Craparo, Barbara Porsio, Domenico Schillaci, Maria G Cusimano, Dario Spigolon, Gaetano Giammona, Gennara Cavallaro
AIM: Efficacy of antibiotics in cystic fibrosis (CF) is compromised by the poor penetration through mucus barrier. This work proposes a new 'nano-into-micro' approach, used to obtain a combinatorial effect: achieve a sustained delivery of tobramycin and overcome mucus barrier. METHODS: Mannitol microparticles (MPs) were loaded with a tobramycin polymeric nanocomplex and characterized in presence of CF artificial mucus. RESULTS & DISCUSSION: MPs are able to alter the rheological properties of CF artificial mucus, enhancing drug penetration into it and allowing a prolonged drug release...
January 2017: Nanomedicine
Neeraj Vij
ΔF508-CFTR (cystic fibrosis transmembrane conductance regulator) is a common CF-mutation that is known to induce oxidative-inflammatory stress through activation of reactive oxygen species (ROS), which induces autophagy-impairment resulting in accumulation of CFTR in aggresome-bodies. Cysteamine, the reduced form of cystamine, is a FDA-approved drug that has anti-oxidant, anti-bacterial, and mucolytic properties. This drug has been shown in a recent clinical trial to decrease lung inflammation and improve lung function in CF patients by potentially restoring autophagy and allowing CFTR to be trafficked to the cell membrane...
April 2017: Expert Opinion on Drug Delivery
Zahra Merchant, Graham Buckton, Kevin M G Taylor, Paul Stapleton, Imran Y Saleem, Mohammed G Zariwala, Satyanarayana Somavarapu
Pulmonary infections may be fatal especially in immunocompromised patients and patients with underlying pulmonary dysfunction, such as those with cystic fibrosis, chronic obstructive pulmonary disorder, etc. According to the WHO, lower respiratory tract infections ranked first amongst the leading causes of death in 2012, and tuberculosis was included in the top 10 causes of death in low income countries, placing a considerable strain on their economies and healthcare systems. Eradication of lower respiratory infections is arduous, leading to high healthcare costs and requiring higher doses of antibiotics to reach optimal concentrations at the site of pulmonary infection for protracted periods...
2016: Current Pharmaceutical Design
Ivana d'Angelo, Bruno Casciaro, Agnese Miro, Fabiana Quaglia, Maria Luisa Mangoni, Francesca Ungaro
Cationic antimicrobial peptides (CAMPs) are very promising in the treatment of multi-drug resistant Pseudomonas aeruginosa lung infections experienced by cystic fibrosis (CF) patients. Nevertheless, there is an urgent need of inhalable formulations able to deliver the intact CAMP in conductive airways and to shield its interactions with airway mucus/bacterial biofilm, thus enhancing CAMP/bacteria interactions. Along these lines, the aim of this work was the design and development of nano-embedded microparticles (NEM) for sustained delivery of CAMPs in the lung...
November 1, 2015: Colloids and Surfaces. B, Biointerfaces
Jill Deacon, Sharif M Abdelghany, Derek J Quinn, Daniela Schmid, Julianne Megaw, Ryan F Donnelly, David S Jones, Adrien Kissenpfennig, J Stuart Elborn, Brendan F Gilmore, Clifford C Taggart, Christopher J Scott
Inhaled antibiotics, such as tobramycin, for the treatment of Pseudomonas aeruginosa pulmonary infections are associated with the increase in life expectancy seen in cystic fibrosis (CF) patients over recent years. However, the effectiveness of this aminoglycoside is still limited by its inability to penetrate the thick DNA-rich mucus in the lungs of these patients, leading to low antibiotic exposure to resident bacteria. In this study, we created novel polymeric nanoparticle (NP) delivery vehicles for tobramycin...
January 28, 2015: Journal of Controlled Release: Official Journal of the Controlled Release Society
Noha Nafee, Ayman Husari, Christine K Maurer, Cenbin Lu, Chiara de Rossi, Anke Steinbach, Rolf W Hartmann, Claus-Michael Lehr, Marc Schneider
Cystic fibrosis (CF) is a genetic disease mainly manifested in the respiratory tract. Pseudomonas aeruginosa (P. aeruginosa) is the most common pathogen identified in cultures of the CF airways, however, its eradication with antibiotics remains challenging as it grows in biofilms that counterwork human immune response and dramatically decrease susceptibility to antibiotics. P. aeruginosa regulates pathogenicity via a cell-to-cell communication system known as quorum sensing (QS) involving the virulence factor (pyocyanin), thus representing an attractive target for coping with bacterial pathogenicity...
October 28, 2014: Journal of Controlled Release: Official Journal of the Controlled Release Society
Tony Le Gall, Mathieu Berchel, Sophie Le Hir, Aurore Fraix, Jean Yves Salaün, Claude Férec, Pierre Lehn, Paul-Alain Jaffrès, Tristan Montier
Gene therapy of diseases like cystic fibrosis (CF) would consist of delivering a gene medicine towards the lungs via the respiratory tract into the target epithelial cells. Accordingly, poly-functional nano-carriers are required in order to overcome the various successive barriers of such a complex environment, such as airway colonization with bacterial strains. In this work, the antibacterial effectiveness of a series of cationic lipids is investigated before evaluating its compatibility with gene transfer into human bronchial epithelial cells...
November 2013: Advanced Healthcare Materials
Neeraj Vij
Chronic airway inflammation is a hallmark of chronic obstructive airway diseases, including asthma, COPD (chronic obstructive pulmonary disease), and CF (cystic fibrosis). It is also a major challenge in delivery and therapeutic efficacy of nano-based delivery systems in these chronic airway conditions as nanoparticle (NP) need to bypass airways defense mechanisms as we recently discussed. NPs which are capable of overcoming airways defense mechanisms should allow targeted drug delivery to disease cells. Over the last decade there has been increasing interest in development of targeted NPs for cancer but relatively little effort on designing novel systems for treating chronic inflammatory and obstructive airway conditions...
2012: Methods in Molecular Biology
Krzysztof J Reszka, Ye Xiong, Larry Sallans, Rajamouli Pasula, Oyebode Olakanmi, Daniel J Hassett, Bradley E Britigan
Pyocyanin (1-hydroxy-N-methylphenazine, PCN) is a cytotoxic pigment and virulence factor secreted by the human bacterial pathogen, Pseudomonas aeruginosa. Here, we report that exposure of PCN to airway peroxidases, hydrogen peroxide (H(2)O(2)), and NaNO(2) generates unique mononitrated PCN metabolites (N-PCN) as revealed by HPLC/mass spectrometry analyses. N-PCN, in contrast to PCN, was devoid of antibiotic activity and failed to kill Escherichia coli and Staphylococcus aureus. Furthermore, in contrast to PCN, intratracheal instillation of N-PCN into murine lungs failed to induce a significant inflammatory response...
May 15, 2012: American Journal of Physiology. Lung Cellular and Molecular Physiology
Neeraj Vij
The major challenges in the delivery and therapeutic efficacy of nano-delivery systems in chronic obstructive airway conditions are airway defense, severe inflammation and mucous hypersecretion. Chronic airway inflammation and mucous hypersecretion are hallmarks of chronic obstructive airway diseases, including asthma, COPD (chronic obstructive pulmonary disease) and CF (cystic fibrosis). Distinct etiologies drive inflammation and mucous hypersecretion in these diseases, which are further induced by infection or components of cigarette smoke...
September 2011: Expert Opinion on Drug Delivery
Neeraj Vij, Taehong Min, Rhul Marasigan, Christopher N Belcher, Steven Mazur, Hong Ding, Ken-Tye Yong, Indrajit Roy
BACKGROUND: The mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene results in CF. The most common mutation, ΔF508-CFTR, is a temperature-sensitive, trafficking mutant with reduced chloride transport and exaggerated immune response. The ΔF508-CFTR is misfolded, ubiquitinated, and prematurely degraded by proteasome mediated- degradation. We recently demonstrated that selective inhibition of proteasomal pathway by the FDA approved drug PS-341 (pyrazylcarbonyl-Phe-Leuboronate, a...
September 24, 2010: Journal of Nanobiotechnology
Peter L Pedersen
Transport ATPases can be lumped into four distinct types, P, F, V, and ABC, with the first three designated 20 years ago (Pedersen, P.L. and Carafoli, E., Trends Biochem. Sci. 12, 146-150, 1987) and the ABC type included more recently. The mini-reviews (>20) that comprise this volume of the Journal of Bioenergetics and Biomembranes describe work presented at the 2007 FASEB Conference (6th) on Transport ATPases (Kathleen Sweadner, Chair; Rajini Rao, Co-Chair). Since these conferences began in 1997, the "transport ATPase field" has seen tremendous progress...
December 2007: Journal of Bioenergetics and Biomembranes
Jon Dobson
Most research in the area of micro- and nano-particles as applied to respiratory disease has been on potential toxic effects. Particulate emissions from industrial processes, coal burning and diesel exhaust have been shown to cause a variety of adverse effects both in vitro and in vivo. However, the vast majority of these studies has focused on larger, micron-sized particles. It is only within the last few years that the emphasis has shifted to nanoparticles as nanotechnology research and its applications have increased...
March 2007: Paediatric Respiratory Reviews
Mahavir Bhupal Chougule, Bijay Kumar Padhi, Ambikanandan Misra
The purpose of this study was to encapsulate Amiloride Hydrochloride into nano-liposomes, incorporate it into dry powder inhaler, and to provide prolonged effective concentration in airways to enhance mucociliary clearance and prevent secondary infection in cystic fibrosis. Liposomes were prepared by thin film hydration technique and then dispersion was passed through high pressure homogenizer to achieve size of nanometer range. Nano-liposomes were separated by centrifugation and were characterized. They were dispersed in phosphate buffer saline pH 7...
September 2006: Journal of Nanoscience and Nanotechnology
E Kleemann, M Neu, N Jekel, L Fink, T Schmehl, T Gessler, W Seeger, T Kissel
Gene therapy aimed at the respiratory epithelium holds therapeutic potential for diseases such as cystic fibrosis and lung cancer. Polyethylenimine (PEI) has been utilized for gene delivery to the airways. In this study, we describe a new modification of PEI, in which an oligopeptide related to the protein transduction domain of HIV-1 TAT was covalently coupled to 25 kDa PEI (PEI) through a heterobifunctional polyethylenglycol (PEG) spacer resulting in a TAT-PEG-PEI conjugate. Improved DNA reporter gene complexation and protection was observed for small (approximately 90 nm) polyplexes as well as significantly improved stability against polyanions, Alveofact, bronchial alveolar lining fluid and DNase...
December 5, 2005: Journal of Controlled Release: Official Journal of the Controlled Release Society
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