Controlled surface modification with poly(ethylene)glycol enhances diffusion of PLGA nanoparticles in human cervical mucus.
Drug delivery to mucosal epithelia is severely limited by the mucus gel, which is a physical diffusion barrier as well as an enzymatic barrier in some sites. Loading of drug into polymer particles can protect drugs from degradation and enhance their stability. To improve efficacy of nanoparticulate drug carriers, it has been speculated that polymers such as poly(ethylene)glycol (PEG) incorporated on the particle surface will enhance transport in mucus. In the present study, we demonstrate the direct influence of PEG on surface properties of poly(lactic-co-glycolic)acid (PLGA) nanoparticles (d = 170 +/- 57 nm). PEG of various molecular weights (MW = 2, 5, 10 kDa) were incorporated at a range of densities from 5-100% on the particle surface. Our results indicate PEG addition improves dispersion, neutralize charge, and enhance particle diffusion in cervical mucus in a manner strongly dependent on polymer MW and density. Diffusion of PEGylated particles was 3-10x higher than that of unmodified PLGA particles. These findings improve the understanding of, and confirm a possible direction for, the rational design of effective carriers for mucosal drug/vaccine delivery.
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Department of Biomedical Engineering, Yale University, New Haven, Connecticut 06511, USA.
Saltzman
W Mark
WM
D002582:Cervix Mucus / Q000378:metabolism*; D004058:Diffusion; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry* / Q000378:metabolism*; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D011092:Polyethylene Glycols / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry* / Q000378:metabolism*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013499:Surface Properties; D014867:Water
D014867:Water; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols