Lung inflammation does not affect the clearance kinetics of lipid nanocapsules following pulmonary administration

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Lung inflammation does not affect the clearance kinetics of lipid nanocapsules following pulmonary administration. / Patel, Aateka; Woods, A.; Riffo-vasquez, Yanira; Babin-morgan, Anna; Jones, Marie-christine; Jones, Stuart; Sunassee, Kavitha; Clark, Stephen; T. M. De Rosales, Rafael; Page, Clive; Spina, Domenico; Forbes, Ben; Dailey, Lea Ann.

In: Journal of Controlled Release, Vol. 235, 10.08.2016, p. 24-33.

Research output: Contribution to journalArticlepeer-review

Harvard

Patel, A, Woods, A, Riffo-vasquez, Y, Babin-morgan, A, Jones, M, Jones, S, Sunassee, K, Clark, S, T. M. De Rosales, R, Page, C, Spina, D, Forbes, B & Dailey, LA 2016, 'Lung inflammation does not affect the clearance kinetics of lipid nanocapsules following pulmonary administration', Journal of Controlled Release, vol. 235, pp. 24-33. https://doi.org/10.1016/j.jconrel.2016.05.024

APA

Patel, A., Woods, A., Riffo-vasquez, Y., Babin-morgan, A., Jones, M., Jones, S., Sunassee, K., Clark, S., T. M. De Rosales, R., Page, C., Spina, D., Forbes, B., & Dailey, L. A. (2016). Lung inflammation does not affect the clearance kinetics of lipid nanocapsules following pulmonary administration. Journal of Controlled Release, 235, 24-33. https://doi.org/10.1016/j.jconrel.2016.05.024

Vancouver

Author

Patel, Aateka ; Woods, A. ; Riffo-vasquez, Yanira ; Babin-morgan, Anna ; Jones, Marie-christine ; Jones, Stuart ; Sunassee, Kavitha ; Clark, Stephen ; T. M. De Rosales, Rafael ; Page, Clive ; Spina, Domenico ; Forbes, Ben ; Dailey, Lea Ann. / Lung inflammation does not affect the clearance kinetics of lipid nanocapsules following pulmonary administration. In: Journal of Controlled Release. 2016 ; Vol. 235. pp. 24-33.

Bibtex

@article{2612e71ef5754ab9a4ad2341dd6f5108,
title = "Lung inflammation does not affect the clearance kinetics of lipid nanocapsules following pulmonary administration",
abstract = "Lipid nanocapsules (LNCs) are semi-rigid spherical capsules with a triglyceride core that present a promising formulation option for the pulmonary delivery of drugs with poor aqueous solubility. Whilst the biodistribution of LNCs of different size has been studied following intravenous administration, the fate of LNCs following pulmonary delivery has not been reported. We investigated quantitatively whether lung inflammation affects the clearance of 50 nm lipid nanocapsules, or is exacerbated by their pulmonary administration. Studies were conducted in mice with lipopolysaccharide-induced lung inflammation compared to healthy controls. Particle deposition and nanocapsule clearance kinetics were measured by single photon emission computed tomography/computed tomography (SPECT/CT) imaging over 48 h. A significantly lower lung dose of 111In-LNC50 was achieved in the lipopolysaccharide (LPS)-treated animals compared with healthy controls (p < 0.001). When normalised to the delivered lung dose, the clearance kinetics of 111In-LNC50 from the lungs fit a first order model with an elimination half-life of 10.5 ± 0.9 h (R2 = 0.995) and 10.6 ± 0.3 h (R2 = 1.000) for healthy and inflamed lungs respectively (n = 3). In contrast, 111In-diethylene triamine pentaacetic acid (DTPA), a small hydrophilic molecule, was cleared rapidly from the lungs with the majority of the dose absorbed within 20 min of administration. Biodistribution to lungs, stomach-intestine, liver, trachea-throat and blood at the end of the imaging period was unaltered by lung inflammation. This study demonstrated that lung clearance and whole body distribution of lipid nanocapsules were unaffected by the presence of acute lung inflammation.",
keywords = "Lipid nanocapsules, Pulmonary drug delivery, Biodistribution, SPECT/CT, Lung clearance kinetics, Inflammation",
author = "Aateka Patel and A. Woods and Yanira Riffo-vasquez and Anna Babin-morgan and Marie-christine Jones and Stuart Jones and Kavitha Sunassee and Stephen Clark and {T. M. De Rosales}, Rafael and Clive Page and Domenico Spina and Ben Forbes and Dailey, {Lea Ann}",
year = "2016",
month = aug,
day = "10",
doi = "10.1016/j.jconrel.2016.05.024",
language = "English",
volume = "235",
pages = "24--33",
journal = "Journal of Controlled Release",
issn = "0168-3659",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Lung inflammation does not affect the clearance kinetics of lipid nanocapsules following pulmonary administration

AU - Patel, Aateka

AU - Woods, A.

AU - Riffo-vasquez, Yanira

AU - Babin-morgan, Anna

AU - Jones, Marie-christine

AU - Jones, Stuart

AU - Sunassee, Kavitha

AU - Clark, Stephen

AU - T. M. De Rosales, Rafael

AU - Page, Clive

AU - Spina, Domenico

AU - Forbes, Ben

AU - Dailey, Lea Ann

PY - 2016/8/10

Y1 - 2016/8/10

N2 - Lipid nanocapsules (LNCs) are semi-rigid spherical capsules with a triglyceride core that present a promising formulation option for the pulmonary delivery of drugs with poor aqueous solubility. Whilst the biodistribution of LNCs of different size has been studied following intravenous administration, the fate of LNCs following pulmonary delivery has not been reported. We investigated quantitatively whether lung inflammation affects the clearance of 50 nm lipid nanocapsules, or is exacerbated by their pulmonary administration. Studies were conducted in mice with lipopolysaccharide-induced lung inflammation compared to healthy controls. Particle deposition and nanocapsule clearance kinetics were measured by single photon emission computed tomography/computed tomography (SPECT/CT) imaging over 48 h. A significantly lower lung dose of 111In-LNC50 was achieved in the lipopolysaccharide (LPS)-treated animals compared with healthy controls (p < 0.001). When normalised to the delivered lung dose, the clearance kinetics of 111In-LNC50 from the lungs fit a first order model with an elimination half-life of 10.5 ± 0.9 h (R2 = 0.995) and 10.6 ± 0.3 h (R2 = 1.000) for healthy and inflamed lungs respectively (n = 3). In contrast, 111In-diethylene triamine pentaacetic acid (DTPA), a small hydrophilic molecule, was cleared rapidly from the lungs with the majority of the dose absorbed within 20 min of administration. Biodistribution to lungs, stomach-intestine, liver, trachea-throat and blood at the end of the imaging period was unaltered by lung inflammation. This study demonstrated that lung clearance and whole body distribution of lipid nanocapsules were unaffected by the presence of acute lung inflammation.

AB - Lipid nanocapsules (LNCs) are semi-rigid spherical capsules with a triglyceride core that present a promising formulation option for the pulmonary delivery of drugs with poor aqueous solubility. Whilst the biodistribution of LNCs of different size has been studied following intravenous administration, the fate of LNCs following pulmonary delivery has not been reported. We investigated quantitatively whether lung inflammation affects the clearance of 50 nm lipid nanocapsules, or is exacerbated by their pulmonary administration. Studies were conducted in mice with lipopolysaccharide-induced lung inflammation compared to healthy controls. Particle deposition and nanocapsule clearance kinetics were measured by single photon emission computed tomography/computed tomography (SPECT/CT) imaging over 48 h. A significantly lower lung dose of 111In-LNC50 was achieved in the lipopolysaccharide (LPS)-treated animals compared with healthy controls (p < 0.001). When normalised to the delivered lung dose, the clearance kinetics of 111In-LNC50 from the lungs fit a first order model with an elimination half-life of 10.5 ± 0.9 h (R2 = 0.995) and 10.6 ± 0.3 h (R2 = 1.000) for healthy and inflamed lungs respectively (n = 3). In contrast, 111In-diethylene triamine pentaacetic acid (DTPA), a small hydrophilic molecule, was cleared rapidly from the lungs with the majority of the dose absorbed within 20 min of administration. Biodistribution to lungs, stomach-intestine, liver, trachea-throat and blood at the end of the imaging period was unaltered by lung inflammation. This study demonstrated that lung clearance and whole body distribution of lipid nanocapsules were unaffected by the presence of acute lung inflammation.

KW - Lipid nanocapsules

KW - Pulmonary drug delivery

KW - Biodistribution

KW - SPECT/CT

KW - Lung clearance kinetics

KW - Inflammation

U2 - 10.1016/j.jconrel.2016.05.024

DO - 10.1016/j.jconrel.2016.05.024

M3 - Article

VL - 235

SP - 24

EP - 33

JO - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

ER -