PMID- 19053536 OWN - NLM STAT- MEDLINE DCOM- 20090323 LR - 20220318 IS - 1543-8384 (Print) IS - 1543-8392 (Electronic) IS - 1543-8384 (Linking) VI - 6 IP - 1 DP - 2009 Jan-Feb TI - Controlled surface modification with poly(ethylene)glycol enhances diffusion of PLGA nanoparticles in human cervical mucus. PG - 173-81 LID - 10.1021/mp8001254 [doi] AB - 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. FAU - Cu, Yen AU - Cu Y AD - Department of Biomedical Engineering, Yale University, New Haven, Connecticut 06511, USA. FAU - Saltzman, W Mark AU - Saltzman WM LA - eng GR - R01 EB000487-15/EB/NIBIB NIH HHS/United States GR - R56 EB000487-18A1/EB/NIBIB NIH HHS/United States GR - R01 EB000487-17/EB/NIBIB NIH HHS/United States GR - R01 EB000487-13/EB/NIBIB NIH HHS/United States GR - R01 EB000487/EB/NIBIB NIH HHS/United States GR - R01 EB000487-14/EB/NIBIB NIH HHS/United States GR - R56 EB000487/EB/NIBIB NIH HHS/United States GR - R01 EB000487-16/EB/NIBIB NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - Mol Pharm JT - Molecular pharmaceutics JID - 101197791 RN - 059QF0KO0R (Water) RN - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer) RN - 26009-03-0 (Polyglycolic Acid) RN - 33X04XA5AT (Lactic Acid) RN - 3WJQ0SDW1A (Polyethylene Glycols) SB - IM MH - Cervix Mucus/*metabolism MH - Diffusion MH - Humans MH - Lactic Acid/*chemistry/*metabolism MH - Microscopy, Electron, Scanning MH - Nanoparticles/*chemistry/ultrastructure MH - Polyethylene Glycols/*chemistry MH - Polyglycolic Acid/*chemistry/*metabolism MH - Polylactic Acid-Polyglycolic Acid Copolymer MH - Surface Properties MH - Water PMC - PMC2637413 MID - NIHMS86566 EDAT- 2008/12/05 09:00 MHDA- 2009/03/24 09:00 PMCR- 2010/01/01 CRDT- 2008/12/05 09:00 PHST- 2008/12/05 09:00 [pubmed] PHST- 2009/03/24 09:00 [medline] PHST- 2008/12/05 09:00 [entrez] PHST- 2010/01/01 00:00 [pmc-release] AID - 10.1021/mp8001254 [pii] AID - 10.1021/mp8001254 [doi] PST - ppublish SO - Mol Pharm. 2009 Jan-Feb;6(1):173-81. doi: 10.1021/mp8001254.