Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus

@article{citeulike:2460920, abstract = {Nanoparticles larger than the reported mesh-pore size range (10-200 nm) in mucus have been thought to be much too large to undergo rapid diffusional transport through mucus barriers. However, large nanoparticles are preferred for higher drug encapsulation efficiency and the ability to provide sustained delivery of a wider array of drugs. We used high-speed multiple-particle tracking to quantify transport rates of individual polymeric particles of various sizes and surface chemistries in samples of fresh human cervicovaginal mucus. Both the mucin concentration and viscoelastic properties of these cervicovaginal samples are similar to those in many other human mucus secretions. Unexpectedly, we found that large nanoparticles, 500 and 200 nm in diameter, if coated with polyethylene glycol, diffused through mucus with an effective diffusion coefficient (Deff) only 4- and 6-fold lower than that for the same particles in water (at time scale {tau} = 1 s). In contrast, for smaller but otherwise identical 100-nm coated particles, Deff was 200-fold lower in mucus than in water. For uncoated particles 100-500 nm in diameter, Deff was 2,400- to 40,000-fold lower in mucus than in water. Much larger fractions of the 100-nm particles were immobilized or otherwise hindered by mucus than the large 200- to 500-nm particles. Thus, in contrast to the prevailing belief, these results demonstrate that large nanoparticles, if properly coated, can rapidly penetrate physiological human mucus, and they offer the prospect that large nanoparticles can be used for mucosal drug delivery. 10.1073/pnas.0608611104}, author = {Lai, Samuel K. and O'Hanlon, Elizabeth D. and Harrold, Suzanne and Man, Stan T. and Wang, Ying-Ying and Cone, Richard and Hanes, Justin }, citeulike-article-id = {2460920}, doi = {http://dx.doi.org/10.1073/pnas.0608611104}, journal = {Proceedings of the National Academy of Sciences}, keywords = {drug\_delivery, mucosal\_barrier, nanoparticles, peg}, month = {January}, number = {5}, pages = {1482--1487}, posted-at = {2008-03-03 14:10:51}, priority = {2}, title = {Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus}, url = {http://dx.doi.org/10.1073/pnas.0608611104}, volume = {104}, year = {2007} }

TY - JOUR ID - citeulike:2460920 L3 - citeulike-article-id:2460920 TI - Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus JF - Proceedings of the National Academy of Sciences VL - 104 IS - 5 SP - 1482 EP - 1487 N2 - Nanoparticles larger than the reported mesh-pore size range (10-200 nm) in mucus have been thought to be much too large to undergo rapid diffusional transport through mucus barriers. However, large nanoparticles are preferred for higher drug encapsulation efficiency and the ability to provide sustained delivery of a wider array of drugs. We used high-speed multiple-particle tracking to quantify transport rates of individual polymeric particles of various sizes and surface chemistries in samples of fresh human cervicovaginal mucus. Both the mucin concentration and viscoelastic properties of these cervicovaginal samples are similar to those in many other human mucus secretions. Unexpectedly, we found that large nanoparticles, 500 and 200 nm in diameter, if coated with polyethylene glycol, diffused through mucus with an effective diffusion coefficient (Deff) only 4- and 6-fold lower than that for the same particles in water (at time scale {tau} = 1 s). In contrast, for smaller but otherwise identical 100-nm coated particles, Deff was 200-fold lower in mucus than in water. For uncoated particles 100-500 nm in diameter, Deff was 2,400- to 40,000-fold lower in mucus than in water. Much larger fractions of the 100-nm particles were immobilized or otherwise hindered by mucus than the large 200- to 500-nm particles. Thus, in contrast to the prevailing belief, these results demonstrate that large nanoparticles, if properly coated, can rapidly penetrate physiological human mucus, and they offer the prospect that large nanoparticles can be used for mucosal drug delivery. 10.1073/pnas.0608611104 KW - drug_delivery KW - mucosal_barrier KW - nanoparticles KW - peg AU - Lai, Samuel AU - O'Hanlon, Elizabeth AU - Harrold, Suzanne AU - Man, Stan AU - Wang, Ying-Ying AU - Cone, Richard AU - Hanes, Justin PY - 2007/01/30/ UR - http://dx.doi.org/10.1073/pnas.0608611104 ER -