title: Development of biodegradable hyperbranched core-multishell nanocarriers for efficient topical drug delivery.
abstract: The topical application of drugs allows for a local application in skin disease and can reduce side effects. Here we present biodegradable core-multishell (CMS) nanocarriers which are composed of a hyperbranched polyglycerol core functionalized with diblock copolymers consisting of polycaprolactone (PCL) and poly(ethylene glycol) (mPEG) as the outer shell. The anti-inflammatory drug Dexamethasone (Dexa) was loaded into these CMS nanocarriers. DLS results suggested that Dexa loaded nanoparticles mostly act as a unimolecular carrier system. With longer PCL segments, a better transport capacity is observed. In vitro skin permeation studies showed that CMS nanocarriers could improve the Nile red penetration through the skin by up to 7 times, compared to a conventional cream formulation. Interestingly, covalently FITC-labeled CMS nanocarriers remain in the stratum corneum layer. This suggests the enhancement is due to the release of cargo after being transported into the stratum corneum by the CMS nanocarriers. In addition, the hPG-PCL-mPEG CMS nanocarriers exhibited good stability, low cytotoxicity, and their production can easily be scaled up, which makes them promising nanocarriers for topical drug delivery.
authors.affiliation: Institut für Organische Chemie und Biochemie, Freie Universität Berlin, Takustraße 3, 14195 Berlin, Germany.
authors.forename: Fang
authors.initials: F
authors.lastname: Du
authors.affiliation: Institute of Pharmacy (Pharmacology and Toxicology), Freie Universität Berlin, 14195 Berlin, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hönzke
authors.affiliation: Institut für Organische Chemie und Biochemie, Freie Universität Berlin, Takustraße 3, 14195 Berlin, Germany; Institute of Biomaterials Science, Helmholtz-Zentrum Geesthacht, 14513 Teltow, Germany.
authors.forename: Falko
authors.initials: F
authors.lastname: Neumann
authors.affiliation: Institut für Organische Chemie und Biochemie, Freie Universität Berlin, Takustraße 3, 14195 Berlin, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Keilitz
authors.affiliation: Institut für Organische Chemie und Biochemie, Freie Universität Berlin, Takustraße 3, 14195 Berlin, Germany.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Institut für Organische Chemie und Biochemie, Freie Universität Berlin, Takustraße 3, 14195 Berlin, Germany; Institute of Biomaterials Science, Helmholtz-Zentrum Geesthacht, 14513 Teltow, Germany.
authors.forename: Nan
authors.initials: N
authors.lastname: Ma
authors.affiliation: Institute of Pharmacy (Pharmacology and Toxicology), Freie Universität Berlin, 14195 Berlin, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Hedtrich
authors.affiliation: Institut für Organische Chemie und Biochemie, Freie Universität Berlin, Takustraße 3, 14195 Berlin, Germany. Electronic address: haag@chemie.fu-berlin.de.
authors.forename: Rainer
authors.initials: R
authors.lastname: Haag
mesh_terms: D000279:Administration, Cutaneous; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003907:Dexamethasone / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D066298:In Vitro Techniques; D053758:Nanoparticles; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption
chemical_list: D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; D011091:Polyesters; C016240:polycaprolactone; D011092:Polyethylene Glycols; D003907:Dexamethasone; C028210:monomethoxypolyethylene glycol
keywords: Core-multishell (CMS) nanocarriers; Dexamethasone; Drug delivery systems; Topical application