Nanomedicine in pulmonary delivery

Mansour, Heidi M.; Rhee, Yun Seok; Wu, Xiao Yu

doi:10.2147/ijn.s4937

Cited by 409 publications

(290 citation statements)

References 229 publications

(210 reference statements)

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“…The human lung adenocarcinoma epithelial cell line A549 is a valuable in vitro model of human alveolar epithelial type 2 cells [15]. This cell line has been widely utilized in the studies of alveolar epithelium function [16] and drug delivery via the lung route [17]. The HEL 12469 cells are human diploid (embryo) lung fibroblasts; these cells were used as a model of normal (healthy) tissue.…”

mentioning

confidence: 99%

The intensity of internalization and cytotoxicity of superparamagnetic iron oxide nanoparticles with different surface modifications in human tumor and diploid lung cells

Mesárošová

Cĭampor²,

Závišová³

et al. 2012

neo

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The human lung adenocarcinoma epithelial (A549) cells and the human embryo lung (HEL 12469) cells were used to investigate the uptake and cytotoxicity of magnetite nanoparticles (MNPs) with different chemically modified surfaces. MNPs uptake was an energy-dependent process substantially affected by the serum concentration in the culture medium. Internalized MNPs localized in vesicle-bound aggregates were observed in the cytoplasm, none in the nucleus or in mitochondria. All MNPs induced a dose-and time-dependent increase in cytotoxicity in both human lung cell lines. The cytotoxicity of MNPs increased proportionally with the particle size. Since the cytotoxicity of MNPs was nearly identical when the doses were equalized based on particle surface area, we suppose that the particle surface area rather than the surface modifications per se underlay the cytotoxicity of MNPs. In general, higher internalized amount of MNPs was found in HEL 12469 cells compared with A549 cells. Accordingly, the viability of the human embryo lung cells was reduced more substantially than that of the adenocarcinoma lung cells. The weak MNPs uptake into A549 cells might be of biomedical relevance in cases where MNPs should be used as nanocarriers for targeted drug delivery in tumor tissue derived from alveolar epithelial cells.

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mentioning

confidence: 99%

The intensity of internalization and cytotoxicity of superparamagnetic iron oxide nanoparticles with different surface modifications in human tumor and diploid lung cells

Mesárošová

Cĭampor²,

Závišová³

et al. 2012

neo

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“…(27) The potential for nanomedicine to improve patient compliance and reduce side effects using respirable particles as drug carriers has made the lung an attractive target for both pulmonary and systemic pharmaceutical delivery. (31)(32)(33) The lung provides a relatively noninvasive route for inspirable drugs, among other advantages including a large surface area to deliver sustainable drug doses and achieve a relatively uniform drug distribution at the alveolar-capillary boundary. (32) For therapeutics to be distributed systemically by respirable particles, the intrinsic defense systems of the FIG.…”

Section: Discussionmentioning

confidence: 99%

“…(31)(32)(33) The lung provides a relatively noninvasive route for inspirable drugs, among other advantages including a large surface area to deliver sustainable drug doses and achieve a relatively uniform drug distribution at the alveolar-capillary boundary. (32) For therapeutics to be distributed systemically by respirable particles, the intrinsic defense systems of the FIG. 5.…”

Section: Discussionmentioning

confidence: 99%

Particulate Matter in Cigarette Smoke Increases Ciliary Axoneme Beating Through Mechanical Stimulation

Navarrette¹,

Sisson²,

Nance

et al. 2012

Journal of Aerosol Medicine and Pulmonary Drug Delivery

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Background: The lung's ability to trap and clear foreign particles via the mucociliary elevator is an important mechanism for protecting the lung against respirable irritants and microorganisms. Although cigarette smoke (CS) exposure and particulate inhalation are known to alter mucociliary clearance, little is known about how CS and nanoparticles (NPs) modify cilia beating at the cytoskeletal infrastructure, or axonemal, level. Methods: We used a cell-free model to introduce cigarette smoke extract (CSE) and NPs with variant size and surface chemistry to isolated axonemes and measured changes in ciliary motility. We hypothesized that CSE would alter cilia beating and that alterations in ciliary beat frequency (CBF) due to particulate matter would be size-and surface chemistry-dependent. Demembranated axonemes were isolated from ciliated bovine tracheas and exposed to adenosine triphosphate (ATP) to initiate motility. CBF was measured in response to 5% CSE, CSE filtrate, and carboxyl-modified (COOH), sulphate (SO 4 )-modified (sulfonated), or PEG-coated polystyrene (PS) latex NPs ranging in size from 40 nm to 500 nm. Results: CSE concentrations as low as 5% resulted in rapid, significant stimulation of CBF ( p < 0.05 vs. baseline control). Filtering CSE through a 0.2-lm filter attenuated this effect. Introduction of sulphate-modified PS beads *300 nm in diameter resulted in a similar increase in CBF above baseline ATP levels. Uncharged, PEG-coated beads had no effect on CBF regardless of size. Similarly, COOH-coated particles less than 200 nm in diameter did not alter ciliary motility. However, COOH-coated PS particles larger than 300 nm increased CBF significantly and increased the number of motile points. Conclusions: These data show that NPs, including those found in CSE, mechanically stimulate axonemes in a size-and surface chemistry-dependent manner. Alterations in ciliary motility due to physicochemical properties of NPs may be important for inhalational lung injury and efficient drug delivery of respirable particles.

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“…Another unique property of NPs is the tendency to be phagocytized by alveolar macrophages, if they are in the range of 500–3000 nm [75,76]. The simultaneous effects, of NPs uptake and release, were demonstrated simultaneously, when a study of multilamellar liposomes containing rifampicin and isoniazid exhibited presence in alveolar macrophages and could maintain therapeutic concentrations in the lung tissue for 5 days [77].…”

Section: General Approaches For Targeting Pulmonary Delivery Of Macromentioning

confidence: 99%

Carriers for the targeted delivery of aerosolized macromolecules for pulmonary pathologies

Osman

Kaneko

Carini

et al. 2018

Expert Opinion on Drug Delivery

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Introduction: Macromolecules with unique effects and potency are increasingly being considered for application in lung pathologies. Numerous delivery strategies for these macromolecules through the lung have been investigated to improve the targeting and overall efficacy.Areas covered: Targeting approaches from delivery devices, formulation strategies and specific targets are discussed.Expert opinion: Although macromolecules are a heterogeneous group of molecules, a number of strategies have been investigated at the macro, micro, and nanoscopic scale for the delivery of macromolecules to specific sites and cells of lung tissues. Targeted approaches are already in use at the macroscopic scale through inhalation devices and formulations, but targeting strategies at the micro and nanoscopic scale are still in the laboratory stage. The combination of controlling lung deposition and targeting after deposition, through a combination of targeting strategies could be the future direction for the treatment of lung pathologies through the pulmonary route.

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Nanomedicine in pulmonary delivery

Cited by 409 publications

References 229 publications

The intensity of internalization and cytotoxicity of superparamagnetic iron oxide nanoparticles with different surface modifications in human tumor and diploid lung cells

The intensity of internalization and cytotoxicity of superparamagnetic iron oxide nanoparticles with different surface modifications in human tumor and diploid lung cells

Particulate Matter in Cigarette Smoke Increases Ciliary Axoneme Beating Through Mechanical Stimulation

Carriers for the targeted delivery of aerosolized macromolecules for pulmonary pathologies

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