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Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier
Tang B.C.2; Dawson M.2; Lai S.K.2; Wang Y.-Y.1; Suk J.S.1; Yang M.1; Zeitlin P.2; Boyle M.P.1; Fu J.2; Hanes J.2
2009-11-17
Source PublicationProceedings of the National Academy of Sciences of the United States of America
ISSN00278424 10916490
Volume106Issue:46Pages:19268-19273
AbstractProtective mucus coatings typically trap and rapidly remove foreign particles from the eyes, gastrointestinal tract, airways, nasopharynx, and female reproductive tract, thereby strongly limiting opportunities for controlled drug delivery at mucosal surfaces. No synthetic drug delivery system composed of biodegradable polymers has been shown to penetrate highly viscoelastic human mucus, such as non-ovulatory cervicovaginal mucus, at a significant rate. We prepared nanoparticles composed of a biodegradable diblock copolymer of poly(sebacic acid) and poly(ethylene glycol) (PSA-PEG), both of which are routinely used in humans. In fresh undiluted human cervicovaginal mucus (CVM), which has a bulk viscosity approximately 1,800-fold higher than water at low shear, PSA-PEG nanoparticles diffused at an average speed only 12-fold lower than the same particles in pure water. In contrast, similarly sized biodegradable nanoparticles composed of PSA or poly(lactic-co-glycolic acid) (PLGA) diffused at least 3,300-fold slower in CVM than in water. PSA-PEG particles also rapidly penetrated sputum expectorated from the lungs of patients with cystic fibrosis, a disease characterized by hyperviscoelastic mucus secretions. Rapid nanoparticle transport in mucus is made possible by the efficient partitioning of PEG to the particle surface during formulation. Biodegradable polymeric nanoparticles capable of overcoming human mucus barriers and providing sustained drug release open significant opportunities for improved drug and gene delivery at mucosal surfaces.
KeywordCystic fibrosis Drug delivery Gene therapy Mucosa Mucus-penetrating particle
DOI10.1073/pnas.0905998106
URLView the original
Language英語
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Cited Times [WOS]:269   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.The Johns Hopkins School of Medicine
2.Johns Hopkins University
3.The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
4.Georgia Institute of Technology
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GB/T 7714
Tang B.C.,Dawson M.,Lai S.K.,et al. Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier[J]. Proceedings of the National Academy of Sciences of the United States of America,2009,106(46):19268-19273.
APA Tang B.C..,Dawson M..,Lai S.K..,Wang Y.-Y..,Suk J.S..,...&Hanes J..(2009).Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier.Proceedings of the National Academy of Sciences of the United States of America,106(46),19268-19273.
MLA Tang B.C.,et al."Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier".Proceedings of the National Academy of Sciences of the United States of America 106.46(2009):19268-19273.
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