title: A poly(ethylene glycol)-based surfactant for formulation of drug-loaded mucus penetrating particles.
abstract: Mucosal surfaces are protected by a highly viscoelastic and adhesive mucus layer that traps most foreign particles, including conventional drug and gene carriers. Trapped particles are eliminated on the order of seconds to hours by mucus clearance mechanisms, precluding sustained and targeted drug and nucleic acid delivery to mucosal tissues. We have previously shown that polymeric coatings that minimize adhesive interactions with mucus constituents lead to particles that rapidly penetrate human mucus secretions. Nevertheless, a particular challenge in formulating drug-loaded mucus penetrating particles (MPP) is that many commonly used surfactants are either mucoadhesive, or do not facilitate efficient drug encapsulation. We tested a novel surfactant molecule for particle formulation composed of Vitamin E conjugated to 5 kDa poly(ethylene glycol) (VP5k). We show that VP5k-coated poly(lactide-co-glycolide) (PLGA) nanoparticles rapidly penetrate human cervicovaginal mucus, whereas PLGA nanoparticles coated with polyvinyl alcohol or Vitamin E conjugated to 1 kDa PEG were trapped. Importantly, VP5k facilitated high loading of paclitaxel, a frontline chemo drug, into PLGA MPP, with controlled release for at least 4 days and negligible burst release. Our results offer a promising new method for engineering biodegradable, drug-loaded MPP for sustained and targeted delivery of therapeutics at mucosal surfaces.
authors.affiliation: Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N Charles Street, Baltimore, MD 21218, USA.
authors.forename: Olcay
authors.initials: O
authors.lastname: Mert
authors.forename: Samuel K
authors.initials: SK
authors.lastname: Lai
authors.forename: Laura
authors.initials: L
authors.lastname: Ensign
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Wang
authors.forename: Joseph
authors.initials: J
authors.lastname: Wood
authors.forename: Justin
authors.initials: J
authors.lastname: Hanes
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry; D002582:Cervix Mucus / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry; D017239:Paclitaxel / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013501:Surface-Active Agents / Q000737:chemistry*; D014810:Vitamin E / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D013501:Surface-Active Agents; D014810:Vitamin E; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D017239:Paclitaxel