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  • Scalable method to produce biodegradable nanoparticles that rapidly penetrate human mucus.

Scalable method to produce biodegradable nanoparticles that rapidly penetrate human mucus.

Journal of controlled release : official journal of the Controlled Release Society (2013-06-12)
Qingguo Xu, Nicholas J Boylan, Shutian Cai, Bolong Miao, Himatkumar Patel, Justin Hanes
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Mowiol® 10-98, Mw ~61,000
Sigma-Aldrich
Mowiol® 6-98, Mw ~47,000
Sigma-Aldrich
Poly(vinyl alcohol), average Mw 130,000, 99+% hydrolyzed
Sigma-Aldrich
Mowiol® 4-98, Mw ~27,000
Sigma-Aldrich
Mowiol® 8-88, Mw ~67,000
Sigma-Aldrich
Poly(vinyl alcohol), Mw 89,000-98,000, 99+% hydrolyzed
Sigma-Aldrich
Poly(vinyl alcohol), Mw 31,000-50,000, 98-99% hydrolyzed
Sigma-Aldrich
Poly(vinyl alcohol), average Mw 146,000-186,000, 87-89% hydrolyzed
Sigma-Aldrich
Poly(vinyl alcohol), Mw 13,000-23,000, 87-89% hydrolyzed
Sigma-Aldrich
Poly(vinyl alcohol), average Mw 85,000-124,000, 87-89% hydrolyzed
Sigma-Aldrich
Poly(vinyl alcohol), Mw 85,000-124,000, 99+% hydrolyzed
Sigma-Aldrich
Poly(vinyl alcohol), average Mw 31,000-50,000, 87-89% hydrolyzed
Sigma-Aldrich
Poly(vinyl alcohol), Mw 9,000-10,000, 80% hydrolyzed
Sigma-Aldrich
Poly(vinyl alcohol), average Mw 13,000-23,000, 98% hydrolyzed
Sigma-Aldrich
Mowiol® 20-98, Mw ~125,000
Sigma-Aldrich
Resomer® RG 504 H, Poly(D,L-lactide-co-glycolide), acid terminated, lactide:glycolide 50:50, Mw 38,000-54,000
Sigma-Aldrich
Poly(vinyl alcohol), Fully hydrolyzed
Sigma-Aldrich
Mowiol® 4-88, Mw ~31,000
Sigma-Aldrich
Poly(vinyl alcohol), 87-90% hydrolyzed, average mol wt 30,000-70,000
Sigma-Aldrich
Poly(vinyl alcohol), Mw 146,000-186,000, 99+% hydrolyzed
Sigma-Aldrich
Resomer® RG 505, Poly(D,L-lactide-co-glycolide), ester terminated, Mw 54,000-69,000
Sigma-Aldrich
Mowiol® 18-88, Mw ~130,000
Sigma-Aldrich
Mowiol® 56-98, Mw ~195,000
Sigma-Aldrich
Poly(D,L-lactide-co-glycolide), ester terminated, Mw 50,000-75,000
Sigma-Aldrich
Mowiol® 40-88, average Mw ~205,000 g/mol
Sigma-Aldrich
Poly(D,L-lactide-co-glycolide), lactide:glycolide (50:50), mol wt 30,000-60,000
Sigma-Aldrich
Poly(D,L-lactide-co-glycolide), lactide:glycolide 65:35, Mw 40,000-75,000
Sigma-Aldrich
Poly(D,L-lactide-co-glycolide), lactide:glycolide (75:25), mol wt 66,000-107,000
Sigma-Aldrich
Resomer® RG 503 H, Poly(D,L-lactide-co-glycolide), acid terminated, lactide:glycolide 50:50, Mw 24,000-38,000
Sigma-Aldrich
Resomer® RG 752 H, Poly(D,L-lactide-co-glycolide), acid terminated, lactide:glycolide 75:25, Mw 4,000-15,000