TY - JOUR
T1 - Scalable method to produce biodegradable nanoparticles that rapidly penetrate human mucus
AU - Xu, Qingguo
AU - Boylan, Nicholas J.
AU - Cai, Shutian
AU - Miao, Bolong
AU - Patel, Himatkumar
AU - Hanes, Justin
N1 - Funding Information:
We thank the Wilmer Microscopy and Imaging Core Facility. Dr. John Baty and the Department of Conservation and Preservation at Johns Hopkins University are acknowledged for GPC measurements. We are grateful to Dr. Y.Y. Wang for her comments to the paper. This work is supported in part by the NIH NIAID R33AI079740 , NCI U54CA151838 and NHLBI P50HL107190 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the National Cancer Institute.
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - Drug delivery
KW - Emulsification
KW - Mucus-penetrating particles
KW - Nanomedicine
KW - Surface PEG density
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U2 - 10.1016/j.jconrel.2013.05.035
DO - 10.1016/j.jconrel.2013.05.035
M3 - Article
C2 - 23751567
AN - SCOPUS:84879482486
SN - 0168-3659
VL - 170
SP - 279
EP - 286
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 2
ER -