scholarly journals Uniformity and Efficacy of Dry Powders Delivered to the Lungs of a Mycobacterial-Surrogate Rat Model of Tuberculosis

Author(s):  
Keiji Hirota ◽  
Yutaka Hirai ◽  
Takehisa Nakajima ◽  
Satoru Goto ◽  
Kimiko Makino ◽  
...  

Abstract Purpose Pulmonary administration of dry drug powder is a considered promising strategy in the treatment of various lung diseases such as tuberculosis and is more effective than systemic medication. However, in the pre-clinical study phase, there is a lack of devices for effective delivery of dry powders to the lungs of small rodents. In this study, an administration device which utilizes Venturi effect to deliver dry powders to the lungs homogeneously was developed. Methods A Venturi-effect administration device which synchronizes with breathes by use of a ventilator and aerosolizes the dry powders was created. Pulmonary distribution of inhalable dry powders prepared by spray-drying poly(lactic-co-glycolic) acid and an antituberculosis agent rifampicin and anti-tuberculosis effect of the powders on mycobacteria infected rats by administration with the Venturi-effect administration device and a conventional insufflation device were evaluated. Results Homogeneous distribution of the dry powders in the lung was achieved by the Venturi-effect administration device due to efficient and recurring aerosolization of loaded dry powders while synchronizing with breathes. Amount of rifampicin delivered to the lungs by the Venturi-effect administration device was three times higher than that by a conventional insufflation device, demonstrating three times greater antimycobacterial activity. Conclusions The Venturi-effect administration device aerosolized inhalable antituberculosis dry powders efficiently, achieved uniform pulmonary distribution, and aided the dry powders to exert antituberculosis activity on lung-residing mycobacteria.

2017 ◽  
Vol 10 (7) ◽  
pp. 545-552 ◽  
Author(s):  
Silvia Nardelli ◽  
Laura Francesca Pisani ◽  
Gian Eugenio Tontini ◽  
Maurizio Vecchi ◽  
Luca Pastorelli

The Multimatrix® (MMX®) preparation MMX® is a recently obtained drug formulation developed to facilitate release of high concentrations of active drugs into the colon, with a homogeneous distribution along all colonic segments, particularly the most distal ones; the distal colonic tracts, indeed, are the most difficult to reach in significant amounts when a drug is given orally. The MMX® formulation is characterized by a lipophilic matrix dispersed in a hydrophilic structure. Indeed, in the last few years, MMX® technology has been widely used in the development of various drugs for the treatment of inflammatory and infectious gastrointestinal diseases localized in the colon. In particular, MMX® mesalamine, budesonide and parnaparin formulations have been investigated in patients with ulcerative colitis, and the first two have reached worldwide registration for the treatment of this disease. Moreover, MMX®-rifamycin is being positively tested in the treatment of colonic bacterial infections, including traveler’s diarrhea. MMX® technology is, thus, proving to be a very effective formulation for the treatment of various colonic diseases. This effectiveness has been related not only to specific colonic delivery, but also to its ability to act in a once-daily dosage, thus favouring patients’ adherence to prescribed schedules of treatment. The effective delivery of the active molecule to the site of need in the colon is also associated with very low systemic absorption and very low rates of adverse events (AEs). In this paper, we have reviewed all clinical trials performed with an MMX®-bound drug and all possible real-life reports, in order to give an overall evaluation of MMX®.


2021 ◽  
Vol 2021 ◽  
pp. 1-21
Author(s):  
Tian-Liang Ma ◽  
Yong Zhou ◽  
Ci Wang ◽  
Lu Wang ◽  
Jing-Xian Chen ◽  
...  

Ferroptosis is an iron-dependent regulated necrosis characterized by the peroxidation damage of lipid molecular containing unsaturated fatty acid long chain on the cell membrane or organelle membrane after cellular deactivation restitution system, resulting in the cell membrane rupture. Ferroptosis is biochemically and morphologically distinct and disparate from other forms of regulated cell death. Recently, mounting studies have investigated the mechanism of ferroptosis, and numerous proteins play vital roles in regulating ferroptosis. With detailed studies, emerging evidence indicates that ferroptosis is found in multiple lung diseases, demonstrating that ferroptosis appears to be particularly important for lung diseases. The mounting interest in ferroptosis drugs specifically targeting the ferroptosis mechanism holds substantial therapeutic promise in lung diseases. The present review emphatically summarizes the functions and integrated molecular mechanisms of ferroptosis in various lung diseases, proposing that multiangle regulation of ferroptosis might be a promising strategy for the clinical treatment of lung diseases.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1377
Author(s):  
Estefanía Fernández-Paz ◽  
Lucía Feijoo-Siota ◽  
Maria Manuela Gaspar ◽  
Noemi Csaba ◽  
Carmen Remuñán-López

In this work, we propose chitosan (CS)-based nanocapsules (NCs) for pulmonary gene delivery. Hyaluronic acid (HA) was incorporated in the NCs composition (HA/CS NCs) aiming to promote gene transfection in the lung epithelium. NCs were loaded with a model plasmid (pCMV-βGal) to easily evaluate their transfection capacity. The plasmid encapsulation efficiencies were of approx. 90%. To facilitate their administration to the lungs, the plasmid-loaded NCs were microencapsulated in mannitol (Ma) microspheres (MS) using a simple spray-drying technique, obtaining dry powders of adequate properties. In vivo, the MS reached the deep lung, where the plasmid-loaded CS-based NCs were released and transfected the alveolar cells more homogeneously than the control formulation of plasmid directly microencapsulated in Ma MS. The HA-containing formulation achieved the highest transfection efficiency, in a more extended area and more homogeneously distributed than the rest of tested formulations. The new micro-nanostructured platform proposed in this work represents an efficient strategy for the delivery of genetic material to the lung, with great potential for the treatment of genetic lung diseases.


Author(s):  
Arthur J. Wasserman ◽  
Kathy C. Kloos ◽  
David E. Birk

Type I collagen is the predominant collagen in the cornea with type V collagen being a quantitatively minor component. However, the content of type V collagen (10-20%) in the cornea is high when compared to other tissues containing predominantly type I collagen. The corneal stroma has a homogeneous distribution of these two collagens, however, immunochemical localization of type V collagen requires the disruption of type I collagen structure. This indicates that these collagens may be arranged as heterpolymeric fibrils. This arrangement may be responsible for the control of fibril diameter necessary for corneal transparency. The purpose of this work is to study the in vitro assembly of collagen type V and to determine whether the interactions of these collagens influence fibril morphology.


Author(s):  
Peter P. J. L. Verkoeijen ◽  
Remy M. J. P. Rikers ◽  
Henk G. Schmidt

Abstract. The spacing effect refers to the finding that memory for repeated items improves when the interrepetition interval increases. To explain the spacing effect in free-recall tasks, a two-factor model has been put forward that combines mechanisms of contextual variability and study-phase retrieval (e.g., Raaijmakers, 2003 ; Verkoeijen, Rikers, & Schmidt, 2004 ). An important, yet untested, implication of this model is that free recall of repetitions should follow an inverted u-shaped relationship with interrepetition spacing. To demonstrate the suggested relationship an experiment was conducted. Participants studied a word list, consisting of items repeated at different interrepetition intervals, either under incidental or under intentional learning instructions. Subsequently, participants received a free-recall test. The results revealed an inverted u-shaped relationship between free recall and interrepetition spacing in both the incidental-learning condition and the intentional-learning condition. Moreover, for intentionally learned repetitions, the maximum free-recall performance was located at a longer interrepetition interval than for incidentally learned repetitions. These findings are interpreted in terms of the two-factor model of spacing effects in free-recall tasks.


2001 ◽  
Author(s):  
Susan M. Jekielek ◽  
Kristin M. Moore ◽  
Elizabeth C. Hair ◽  
Harriet J. Scarupa

2007 ◽  
Author(s):  
Peter M. Wessels ◽  
Jonathan Schnader ◽  
Allison Smith ◽  
Christopher Thomas ◽  
Haley Titus

Planta Medica ◽  
2009 ◽  
Vol 75 (09) ◽  
Author(s):  
G Da Silva ◽  
A Macedo ◽  
I Famba ◽  
M Taniça ◽  
R Serrano ◽  
...  

Author(s):  
N Buda ◽  
M Piskunowicz ◽  
M Porzezińska ◽  
W Kosiak ◽  
Z Zdrojewski

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