Scalable method to produce biodegradable nanoparticles that rapidly penetrate human mucus

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

Research output: Contribution to journalArticle

Abstract

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
Volume170
Issue number2
DOIs
StatePublished - 2013

Fingerprint

Mucus
Nanoparticles
Molecular Weight
Pharmaceutical Preparations
Polyvinyl Alcohol
Nasopharynx
Biological Products
Immobilization
Intravenous Administration
Adhesives
Gastrointestinal Tract

Keywords

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

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Medicine(all)

Cite this

Scalable method to produce biodegradable nanoparticles that rapidly penetrate human mucus. / Xu, Qingguo; Boylan, Nicholas J.; Cai, Shutian; Miao, Bolong; Patel, Himatkumar; Hanes, Justin S.

In: Journal of Controlled Release, Vol. 170, No. 2, 2013, p. 279-286.

Research output: Contribution to journalArticle

Xu, Qingguo ; Boylan, Nicholas J. ; Cai, Shutian ; Miao, Bolong ; Patel, Himatkumar ; Hanes, Justin S. / Scalable method to produce biodegradable nanoparticles that rapidly penetrate human mucus. In: Journal of Controlled Release. 2013 ; Vol. 170, No. 2. pp. 279-286.
@article{3f4c6325156449678947bc436adca4e5,
title = "Scalable method to produce biodegradable nanoparticles that rapidly penetrate human mucus",
abstract = "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.",
keywords = "Drug delivery, Emulsification, Mucus-penetrating particles, Nanomedicine, Surface PEG density",
author = "Qingguo Xu and Boylan, {Nicholas J.} and Shutian Cai and Bolong Miao and Himatkumar Patel and Hanes, {Justin S}",
year = "2013",
doi = "10.1016/j.jconrel.2013.05.035",
language = "English (US)",
volume = "170",
pages = "279--286",
journal = "Journal of Controlled Release",
issn = "0168-3659",
publisher = "Elsevier",
number = "2",

}

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 S

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

UR - http://www.scopus.com/inward/record.url?scp=84879482486&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84879482486&partnerID=8YFLogxK

U2 - 10.1016/j.jconrel.2013.05.035

DO - 10.1016/j.jconrel.2013.05.035

M3 - Article

C2 - 23751567

AN - SCOPUS:84879482486

VL - 170

SP - 279

EP - 286

JO - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

IS - 2

ER -