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. 2008;47(50):9726-9.
doi: 10.1002/anie.200803526.

Addressing the PEG mucoadhesivity paradox to engineer nanoparticles that "slip" through the human mucus barrier

Ying-Ying Wang  1 , Samuel K Lai, Jung Soo Suk, Amanda Pace, Richard Cone, Justin Hanes
Affiliations

Addressing the PEG mucoadhesivity paradox to engineer nanoparticles that "slip" through the human mucus barrier

Ying-Ying Wang et al. Angew Chem Int Ed Engl. 2008.
No abstract available

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Figures

Figure 1
Figure 1
Transport rates of 200 nm PEG-modified PS particles with high surface coverage 2 kDa PEG (PS-PEG2kHigh) or high surface coverage 10 kDa PEG (PS-PEG10kHigh) in CVM. a) Ensemble-averaged geometric mean square displacements (〈MSD〉) as a function of time scale. b) Distributions of the logarithms of individual particle effective diffusivities (Deff) at a time scale of 1 s. Data represent five independent experiments with n ≥ 100 particles per experiment (average n=141 and 127 for PS-PEG2kHigh and PS-PEG10kHigh, respectively). c) Ratios of the ensemble average diffusion coefficients in mucus (Dm) compared to in water (Dw) for PS-PEG particles with PEG of varying MW. Particles synthesized with a similarly dense coating of 5 kDa methoxy-PEG-amine (PS-PEG5kHigh) had an average size of (238±4) nm and ζ-potential of (-6±1) mV. Data represent three independent experiments with n≥150 particles per experiment for PS-PEG5kHigh.
Figure 2
Figure 2
Transport rates of 200 nm PEG-modified PS particles with higher surface coverage 2 kDa PEG (PS-PEG2kHigh) or lower surface coverage 2 kDa PEG (PS-PEG2kLow) in CVM. a) Ensemble-averaged geometric mean square displacements (〈MSD〉) as a function of time scale. b) Distributions of the logarithms of individual particle effective diffusivities (Deff) at a time scale of 1 s. Data represent five independent experiments with n≥90 particles per experiment (average n = 141 and 132 for PS-PEG2kHigh and PS-PEG2kLow, respectively).
Figure 3
Figure 3
Phase diagram correlating mucoinert versus mucoadhesive particle behavior to surface charge and PEG MW for various PEG-coated nanoparticles (200-500 nm in size) reported herein and in the literature. PEG-coated nanoparticles reported to be non-mucoadhesive compared to control particles are indicated by open symbols, and those reported to be mucoadhesive are indicated by filled symbols. The shaded region represents the confirmed range of PEG MW and particle ζ-potential (i.e., PEG surface coverage), and the hatched region an additional predicted range that provides a mucoinert coating. A) Present study; B) PEG-coated PS nanoparticles;[5] C) PEGylated poly(methyl vinyl ether-co-maleic anhydride) nanoparticles;[16,17] D) poly(lactic acid)-PEG nanoparticles[15] (*: mucoadhesion was not observed based on adhesion to an in vitro mucin-secreting cell line); E) PEG-coated poly(ethyl-2-cyanoacrylate) nanospheres (mucoadhesion was inferred from improved bioavailability compared to free drug).[18]
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