Influence of particle size on regional lung deposition – What evidence is there?

Carvalho, Thiago C.; Peters, Jay I.; Williams, Robert O.

doi:10.1016/j.ijpharm.2010.12.040

Cited by 490 publications

(296 citation statements)

References 88 publications

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“…Hence radiolabeled aerosol particles can be formulated through the same procedure as normal formulation and the same delivery system can be employed for testing in humans. Radionuclide decay time needs to be taken into consideration as these radionuclide have short half-lives (for instance, half-life of 11 C is 20 min and that of 18 F is 110 min) and the preparation of the radiolabeled drug into inhalable dosage form and its loading into the delivery device may consume appreciable amount of time. Furthermore, the procedure of radiolabeling may influence the size of the inhaled particle and significantly affect the observations while investigating the lung deposition patterns of aerosol particles.…”

Section: In Vivo Experimental Methodsmentioning

confidence: 99%

Computational and bioengineered lungs as alternatives to whole animal, isolated organ, and cell-based lung models

Patel

Gauvin

Absar

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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Development of lung models for testing a drug substance or delivery system has been an intensive area of research. However, a model that mimics physiological and anatomical features of human lungs is yet to be established. Although in vitro lung models, developed and fine-tuned over the past few decades, were instrumental for the development of many commercially available drugs, they are suboptimal in reproducing the physiological microenvironment and complex anatomy of human lungs. Similarly, intersubject variability and high costs have been major limitations of using animals in the development and discovery of drugs used in the treatment of respiratory disorders. To address the complexity and limitations associated with in vivo and in vitro models, attempts have been made to develop in silico and tissue-engineered lung models that allow incorporation of various mechanical and biological factors that are otherwise difficult to reproduce in conventional cell or organ-based systems. The in silico models utilize the information obtained from in vitro and in vivo models and apply computational algorithms to incorporate multiple physiological parameters that can affect drug deposition, distribution, and disposition upon administration via the lungs. Bioengineered lungs, on the other hand, exhibit significant promise due to recent advances in stem or progenitor cell technologies. However, bioengineered approaches have met with limited success in terms of development of various components of the human respiratory system. In this review, we summarize the approaches used and advancements made toward the development of in silico and tissue-engineered lung models and discuss potential challenges associated with the development and efficacy of these models. bioengineered lung; computational modeling; in silico; lung models; tissue engineering LUNG DISEASES ARE THE THIRD leading cause of deaths in the United States that translate into one in six deaths. More than 400,000 Americans die of lung disease every year and around 35 million are now living with chronic lung problems (1). Therefore, there is an important need to understand as to how a new drug entity or a novel formulation may influence the anatomy, physiology, and pathogenesis of lungs and vice versa.The human lung has an approximate volume of six liters, contains about 300 million alveoli, and provides a total surface area of 100 square meters as blood-air interface, which is packed into an elastic dynamic structure responsible for gas exchange (159). The human airway wall is a connective tissue that includes smooth muscle cells (SMC), mucus glands, blood vessels, and fibroblasts surrounded by a collagen-rich extracellular matrix (ECM). Epithelial cells, responsible for the efficient oxygen and carbon dioxide transfer, are at the interface between air and the connective tissue and are attached to an underlying basement membrane. The respiratory system is the site of a variety of pulmonary diseases such as asthma, bronchitis, pneumonia, cystic fibrosis, emphysema, a...

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Section: In Vivo Experimental Methodsmentioning

confidence: 99%

Computational and bioengineered lungs as alternatives to whole animal, isolated organ, and cell-based lung models

Patel

Gauvin

Absar

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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show abstract

“…As with DC tracheal tissue, there is a degree of disparity between the effects of different DC protocols on the resultant acellular lung (177,178), and particularly in the case of using lungs that are deemed unsuitable for transplantation, organ storage, donor age and disease status can adversely affect mechanical properties of the resultant scaffold (173,179,180). For now, a more plausible and beneficial clinical application for these whole-organ constructs could be as a sophisticated in vitro drug delivery platform that could provide information on drug deposition fate 26 in the lungs following pulmonary administration, a critical factor in effective delivery to the lungs (181), and systemic absorption, given that the vascular and airway systems remain intact and independent of each other in the DC organ. Furthermore, the use of damaged lung tissue from patients with COPD or other chronic respiratory illness could advance our understanding of the pathogenesis and progression of disease.…”

Section: Decellularised (Dc) Tissuementioning

confidence: 99%

Respiratory Tissue Engineering: Current Status and Opportunities for the Future

O’Leary

Gilbert

O’Dea

et al. 2015

Tissue Engineering Part B: Reviews

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“…In general, the SS 200 morphology appeared to be similar to that reported in previous work, which utilised aqueous solutions to spray dry SS (21,22); while the spray-dried BDP particles were similar in morphology to that reported by Abdel-Halim et al (23), wherein particles were prepared from a 20% w/v ethanolic solution . In general, both particulate systems could be considered of a suitable size for inhalation purposes (24), thus making the study of interactions in 205 medical propellants relative to respiratory drug delivery. To study further the internal structure of these particles, focused ion beam microscopy was utilized to 'dissect' individual micron sized particles.…”

Section: Physicochemical Analysis Of the Spray-dried Model Drugs 195mentioning

confidence: 99%

Isothermal calorimetry: A predictive tool to model drug-propellant interactions in pressurized metered dose systems

Ooi¹,

Gaisford²,

Boyd³

et al. 2014

International Journal of Pharmaceutics

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Influence of particle size on regional lung deposition – What evidence is there?

Cited by 490 publications

References 88 publications

Computational and bioengineered lungs as alternatives to whole animal, isolated organ, and cell-based lung models

Computational and bioengineered lungs as alternatives to whole animal, isolated organ, and cell-based lung models

Respiratory Tissue Engineering: Current Status and Opportunities for the Future

Isothermal calorimetry: A predictive tool to model drug-propellant interactions in pressurized metered dose systems

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