Scalable method to produce biodegradable nanoparticles that rapidly penetrate human mucus

Qingguo Xu, Nicholas J. Boylan, Shutian Cai, Bolong Miao, Himatkumar Patel, Justin Hanes

Research output: Contribution to journalArticlepeer-review

77 Scopus citations


Mucus typically traps and rapidly removes foreign particles from the airways, gastrointestinal tract, nasopharynx, female reproductive tract and the surface of the eye. Nanoparticles capable of rapid penetration through mucus can potentially avoid rapid clearance, and open significant opportunities for controlled drug delivery at mucosal surfaces. Here, we report an industrially scalable emulsification method to produce biodegradable mucus-penetrating particles (MPP). The emulsification of diblock copolymers of poly(lactic-co-glycolic acid) and polyethylene glycol (PLGA-PEG) using low molecular weight (MW) emulsifiers forms dense brush PEG coatings on nanoparticles that allow rapid nanoparticle penetration through fresh undiluted human mucus. In comparison, conventional high MW emulsifiers, such as polyvinyl alcohol (PVA), interrupts the PEG coating on nanoparticles, resulting in their immobilization in mucus owing to adhesive interactions with mucus mesh elements. PLGA-PEG nanoparticles with a wide range of PEG MW (1, 2, 5, and 10 kDa), prepared by the emulsification method using low MW emulsifiers, all rapidly penetrated mucus. A range of drugs, from hydrophobic small molecules to hydrophilic large biologics, can be efficiently loaded into biodegradable MPP using the method described. This readily scalable method should facilitate the production of MPP products for mucosal drug delivery, as well as potentially longer-circulating particles following intravenous administration.

Original languageEnglish (US)
Pages (from-to)279-286
Number of pages8
JournalJournal of Controlled Release
Issue number2
StatePublished - 2013


  • Drug delivery
  • Emulsification
  • Mucus-penetrating particles
  • Nanomedicine
  • Surface PEG density

ASJC Scopus subject areas

  • Pharmaceutical Science


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