Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues

By S. Lai, Ying-Ying Wang, J. Hanes. Advanced Drug Delivery Reviews, 2008

1,733 citations recorded by the source corpus.

Mucus is a viscoelastic and adhesive gel that protects the lung airways, gastrointestinal (GI) tract, vagina, eye and other mucosal surfaces. Most foreign particulates, including conventional particle-based drug delivery systems, are efficiently trapped in human mucus layers by steric obstruction and/or adhesion. Trapped particles are typically removed from the mucosal tissue within seconds to a few hours depending on anatomical location, thereby strongly limiting the duration of sustained drug delivery locally. A number of debilitating diseases could be treated more effectively and with fewer side effects if drugs and genes could be more efficiently delivered to the underlying mucosal tissues in a controlled manner. This review first describes the tenacious mucus barrier properties that have precluded the efficient penetration of therapeutic particles. It then reviews the design and development of new mucus-penetrating particles that may avoid rapid mucus clearance mechanisms, and thereby provide targeted or sustained drug delivery for localized therapies in mucosal tissues.

Subfields: Molecular Biology, Nutrition and Dietetics, Pharmaceutical Science

View Paper: https://www.semanticscholar.org/paper/4376cd6f5067a08dfbac9aa9d2f47c8b7d63ccc1

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. L. Ensign
2. J. Hanes
3. V. Khutoryanskiy
4. A. D'Souza
5. R. Shegokar
6. M. Esteban

In Nutrition and Dietetics

1. R. Cone
2. V. Khutoryanskiy

In Pharmaceutical Science

1. L. Ensign
2. J. Hanes
3. T. M. M. Ways
4. W. Lau
5. V. Khutoryanskiy
6. Xueting Lin
7. B. Homayun
8. Hyo-Jick Choi

Citations in the corpus

• Polyethylene glycol (PEG): a versatile polymer for pharmaceutical applications (2016, background): “[70] PEG-coated carriers influence its transport through mucosal regions of gastrointestinal tract, [71] pulmonary region, [72] cervico vaginal tract, [73] and tumor site.”
• Oral Drug Delivery with Polymeric Nanoparticles: The Gastrointestinal Mucus Barriers (2011, background): “In total, there are at least twenty proteins encoded in the MUC gene family [5], of which, MUC2, MUC5AC, and MUC6 are the secreted mucin types found throughout the GI tract [11].”
• PEGylation as a strategy for improving nanoparticle-based drug and gene delivery (2015, neutral): “However, the viscoelastic and rapidly cleared mucus layers coating the cervicovaginal tract pose a barrier to NP-based drug and gene delivery [122-124].”
• Chitosan and Its Derivatives for Application in Mucoadhesive Drug Delivery Systems (2018, background): “Mucus is a viscoelastic gel lining the mucosal tissues exposed to the external environment including gastrointestinal, respiratory, and reproductive tracts and the eyes [1,2].”
• Mechanism of intranasal drug delivery directly to the brain (2018, background): “These drugs must be absorbed before they are “cleared” by the mucus, which is turned over once every 20 min on average [87].”
• Challenges and Recent Progress in Oral Drug Delivery Systems for Biopharmaceuticals (2019, background): “In addition to this, it is difficult to model the real effects of mucus on delivery carriers in vitro due to its changing thickness along the GI tract and the constant effects of flowing gastric juice [38,67,112].”
• Micro- and macrorheology of mucus (2009, neutral): “However, nanoparticles must efficiently overcome the mucus barrier to avoid rapid clearance [73,74].”