Self-Assembling Nanoparticles Containing Dexamethasone as a Novel Therapy in Allergic Airways Inflammation
Open accessAbstract
Nanocarriers can deliver a wide variety of drugs, target them to sites of interest, and protect them from degradation and inactivation by the body. They have the capacity to improve drug action and decrease undesirable systemic effects. We have previously developed a well-defined non-toxic PEG-dendritic block telodendrimer for successful delivery of chemotherapeutics agents and, in these studies, we apply this technology for therapeutic development in asthma. In these proof-of-concept experiments, we hypothesized that dexamethasone contained in self-assembling nanoparticles (Dex-NP) and delivered systemically would target the lung and decrease allergic lung inflammation and airways hyper-responsiveness to a greater degree than equivalent doses of dexamethasone (Dex) alone. We found that ovalbumin (Ova)-exposed mice treated with Dex-NP had significantly fewer total cells (2.78 ± 0.44 × 10(5) (n = 18) vs. 5.98 ± 1.3 × 10(5) (n = 13), P<0.05) and eosinophils (1.09 ± 0.28 × 10(5) (n = 18) vs. 2.94 ± 0.6 × 10(5) (n = 12), p<0.05) in the lung lavage than Ova-exposed mice alone. Also, lower levels of the inflammatory cytokines IL-4 (3.43 ± 1.2 (n = 11) vs. 8.56 ± 2.1 (n = 8) pg/ml, p<0.05) and MCP-1 (13.1 ± 3.6 (n = 8) vs. 28.8 ± 8.7 (n = 10) pg/ml, p<0.05) were found in lungs of the Dex-NP compared to control, and they were not lower in the Dex alone group. In addition, respiratory system resistance was lower in the Dex-NP compared to the other Ova-exposed groups suggesting a better therapeutic effect on airways hyperresponsiveness. Taken together, these findings from early-stage drug development studies suggest that the encapsulation and protection of anti-inflammatory agents such as corticosteroids in nanoparticle formulations can improve efficacy. Further development of novel drugs in nanoparticles is warranted to explore potential treatments for chronic inflammatory diseases such as asthma.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Telodendrimer-mediated sustained release of dexamethasone decreased allergic lung inflammation compared to equivalent doses of dexamethasone alone.
“The telodendrimer-mediated sustained release of dexamethasone has been found to be effective in decreasing allergic lung inflammation compared to equivalent doses of dexamethasone alone.177”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [177]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Dweik, R. A., Boggs, P. B., Erzurum, S. C., Irvin, C. G., Leigh, M. W., Lundberg, J. O., Olin, A.-C., Plummer, A. L., & Taylor, D. R. (2011) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.9120-11st · Cited by 2,539 · see citing works
Reddel, H. K., Taylor, D. R., Bateman, E. D., Boulet, L., Boushey, H. A., Busse, W. W., Casale, T. B., Chanez, P., Enright, P., Gibson, P. G., et al. (2009) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200801-060st · Cited by 1,918 · see citing works
Lebrikizumab Treatment in Adults with Asthma
Corren, J., Lemanske, R. F., Hanania, N. A., Korenblat, P. E., Parsey, M. V., Arron, J. R., Harris, J. M., Scheerens, H., Wu, L. C., Su, Z., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1106469 · Cited by 1,514 · see citing works
Xiao, K., Li, Y., Luo, J., Lee, J. S., Xiao, W., Gonik, A. M., Agarwal, R. G., & Lam, K. S. (2011) · Biomaterials · doi:10.1016/j.biomaterials.2011.01.021 · Cited by 1,039 · see citing works
Self-citationSchleimer, R. P., Sterbinsky, S. A., Kaiser, J., Bickel, C., Klunk, D. A., Tomioka, K., Newman, W., Luscinskas, F. W., Gimbrone, M. A., & McIntyre, B. W. (1992) · The Journal of Immunology · doi:10.4049/jimmunol.148.4.1086 · Cited by 818 · see citing works
Interleukin-4 Receptor in Moderate Atopic Asthma: A Phase I/II Randomized, Placebo-controlled Trial
Borish, L., Nelson, H. S., Lanz, M. J., Claussen, L. R., Whitmore, J. B., Agosti, J. M., & Garrison, L. (1999) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.160.6.9808146 · Cited by 422 · see citing works
Temelkovski, J., Hogan, S. P., Shepherd, D. P., et al. (1998) · Thorax · doi:10.1136/thx.53.10.849 · Cited by 333 · see citing works
Improvement of drug safety by the use of lipid-based nanocarriers
Lim, S. B., Banerjee, A., & Önyüksel, H. (2012) · Journal of Controlled Release · doi:10.1016/j.jconrel.2012.06.002 · Cited by 325 · see citing works
McFadden, E. R. (2003) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200208-902so · Cited by 316 · see citing works
A Randomized, Controlled, Phase 2 Study of AMG 317, an IL-4Rα Antagonist, in Patients with Asthma
Corren, J., Busse, W. W., Meltzer, E. O., Mansfield, L. E., Bensch, G. W., Fahrenholz, J. M., Wenzel, S. E., Chon, Y., Dunn, M. E., Weng, H. H., et al. (2010) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200909-1448oc · Cited by 299 · see citing works
Li, P., Liu, R., Mařı́k, J., et al. (2006) · Nature Chemical Biology · doi:10.1038/nchembio798 · Cited by 241 · see citing works
A self-assembling nanoparticle for paclitaxel delivery in ovarian cancer
Xiao, K., Luo, J., Fowler, W. L., Li, Y., Lee, J. S., Li, X., Cheng, R. H., Wang, L., & Lam, K. S. (2009) · Biomaterials · doi:10.1016/j.biomaterials.2009.07.015 · Cited by 238 · see citing works
Self-citationSevere asthma: Lessons from the Severe Asthma Research Program
Wenzel, S. E., & Busse, W. W. (2007) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2006.10.025 · Cited by 234 · see citing works
Warheit, D. B., Hansen, J. F., Yuen, I. S., Kelly, D. P., Snajdr, S. I., & Hartsky, M. A. (1997) · Toxicology and Applied Pharmacology · doi:10.1006/taap.1997.8102 · Cited by 165 · see citing works
Simvastatin Inhibits Airway Hyperreactivity: Implications for the Mevalonate Pathway and Beyond
Zeki, A. A., Franzi, L. M., Last, J. A., & Kenyon, N. J. (2009) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200901-0018oc · Cited by 115 · see citing works
Self-citationXiao, K., Luo, J., Li, Y., Lee, J. S., Fung, G., & Lam, K. S. (2011) · Journal of Controlled Release · doi:10.1016/j.jconrel.2011.07.018 · Cited by 110 · see citing works
Self-citationNanoparticulate Systems for Drug Delivery and Targeting to the Central Nervous System
Craparo, E. F., Bondı̀, M. L., Pitarresi, G. L., & Cavallaro, G. (2010) · CNS Neuroscience & Therapeutics · doi:10.1111/j.1755-5949.2010.00199.x · Cited by 94 · see citing works
PM10 impairs the antioxidant defense system and exacerbates oxidative stress driven cell death
Chirino, Y. I., Sánchez-Pérez, Y., Osornio-Vargas, Á. R., Morales‐Bárcenas, R., Gutiérrez‐Ruíz, M. C., Segura-García, Y., Rosas, I., Pedraza‐Chaverrí, J., & García-Cuellar, C. M. (2010) · Toxicology Letters · doi:10.1016/j.toxlet.2010.01.009 · Cited by 93 · see citing works
Why is particulate matter produced by wildfires toxic to lung macrophages?
Franzi, L. M., Bratt, J. M., Williams, K. M., & Last, J. A. (2011) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2011.09.003 · Cited by 84 · see citing works
Self-citationEffects of inhaled nano-TiO2 aerosols showing two distinct agglomeration states on rat lungs
Noël, A., Maghni, K., Cloutier, Y., Dion, C., Wilkinson, K. J., Hallé, S., Tardif, R., & Truchon, G. (2012) · Toxicology Letters · doi:10.1016/j.toxlet.2012.08.019 · Cited by 79 · see citing works
Airway fibrosis in a mouse model of airway inflammation
Kenyon, N. J., Ward, R., & Last, J. A. (2003) · Toxicology and Applied Pharmacology · doi:10.1016/s0041-008x(02)00025-x · Cited by 75 · see citing works
Self-citationUnique and overlapping gene expression patterns driven by IL-4 and IL-13 in the mouse lung
Lewis, C. C., Aronow, B. J., Hutton, J. J., Santeliz, J., Dienger, K. M., Herman, N. S., Finkelman, F. D., & Wills-Karp, M. A. (2009) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2009.01.003 · Cited by 67 · see citing works
Lung response to coarse PM: Bioassay in mice
Wegesser, T. C., & Last, J. A. (2008) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2008.02.013 · Cited by 57 · see citing works
A Method for the Standardized Offline Collection of Exhaled Nitric Oxide
Silkoff, P. E., Stevens, A. D., Pak, J., Bucher‐Bartelson, B., & Martin, R. J. (1999) · CHEST Journal · doi:10.1378/chest.116.3.754 · Cited by 55 · see citing works
T-cell effector pathways in allergic diseases: Transcriptional mechanisms and therapeutic targets
Chatila, T. A., Li, N., Garcia-Lloret, M., Kim, H.-J., & Nel, A. E. (2008) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2008.02.025 · Cited by 53 · see citing works
Korideck, H., & Peterson, J. D. (2009) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.108.147579 · Cited by 50 · see citing works
Raemy, D. O., Grass, R. N., Stark, W. J., Schumacher, C. M., Clift, M. J. D., Gehr, P., & Rothen‐Rutishauser, B. (2012) · Particle and Fibre Toxicology · doi:10.1186/1743-8977-9-33 · Cited by 49 · see citing works
Sánchez‐Moreno, P., Boulaiz, H., Ortega-Vinuesa, J. L., Peula-García, J. M., & Aránega, A. (2012) · International Journal of Molecular Sciences · doi:10.3390/ijms13044906 · Cited by 48 · see citing works
Kenyon, N. J., Bratt, J. M., Linderholm, A., et al. (2008) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2008.03.004 · Cited by 46 · see citing works
Self-citationThe characterization of novel polymeric paste formulations for intratumoral delivery
Jackson, J. K., Zhang, X., Llewellen, S., Hunter, W. L., & Burt, H. M. (2004) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2003.10.010 · Cited by 42 · see citing works
Reduced alveolar macrophage migration induced by acute ambient particle (PM10) exposure
Barlow, P. G., Brown, D. M., Donaldson, K., MacCallum, J., & Stone, V. (2007) · Cell Biology and Toxicology · doi:10.1007/s10565-007-9033-y · Cited by 35 · see citing works
Sahib, M. N., Darwis, Peh, Abdulameer, S. A., & Tan (2012) · Drug Design Development and Therapy · doi:10.2147/dddt.s28265 · Cited by 33 · see citing works
Bratt, J. M., Franzi, L. M., Linderholm, A., et al. (2009) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2009.09.018 · Cited by 31 · see citing works
Self-citationAn α4β1 integrin antagonist decreases airway inflammation in ovalbumin-exposed mice
Kenyon, N. J., Liu, R., O'Roark, E. M., et al. (2008) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2008.11.063 · Cited by 23 · see citing works
Self-citationMcGeehan, M., & Busse, W. W. (2002) · Medical Clinics of North America · doi:10.1016/s0025-7125(02)00034-2 · Cited by 6 · see citing works
Georén, S. K., Tcacencu, I., Wikström, A., et al. (2008) · Acta Oto-Laryngologica · doi:10.1080/00016480802126561 · Cited by 5 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles
Singh, A. P., Biswas, A., Shukla, A., & Maiti, P. (2019) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0068-3 · Cited by 645 · see citing works
- Authors
- Kenyon, N. J., Bratt, J. M., Lee, J., Luo, J., Franzi, L. M., Zeki, A. A., & Lam, K. S.
- Affiliations
- University of California, Davis (US)
- Corresponding author
- Kenyon, Nicholas J.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-10-25
- Volume
- 8
- Issue
- 10
- Pages
- e77730
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3808398
- OpenAlex
- W2060181228
- Cited by
- 53
- References
- 36
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 7 · 2023: 3 · 2022: 5 · 2021: 7 · 2020: 5 · 2019: 5 · 2018: 1 · 2017: 6 · 2016: 5 · 2014: 2 · 2013: 1
- FWCI
- 1.86
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (KL2TR000134)
- National Heart, Lung, and Blood Institute (HL 07013, K08HL114882, R01HL105573, ES-07059, HL 105573, T32HL007013)
- National Cancer Institute (P30CA093373)
- National Institute of Environmental Health Sciences (ES07059, T32ES007059)
- National Institute of Biomedical Imaging and Bioengineering (EB012569, R01EB012569)
- National Center for Advancing Translational Sciences (CTSC KL2, TR000134, HL105573)
- Topics
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
- Keywords
- dexamethasone, nanoparticle self-assembly, asthma, allergic airway inflammation, airway hyperresponsiveness, ovalbumin-induced airway inflammation, corticosteroid delivery, nanocarriers, eosinophils, IL-4, MCP-1, lung lavage, respiratory resistance, systemic drug delivery
- MeSH terms
- Adrenal Cortex Hormones, Animals, Anti-Inflammatory Agents, Asthma, Bronchoalveolar Lavage Fluid, Dexamethasone, Disease Models, Animal, Lung, Male, Mice, Inbred BALB C, Nitric Oxide, Ovalbumin, Pneumonia, Interleukin-4, Chemokine CCL2, Mice, Nanoparticles
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
