title: Impact of structural differences in hyperbranched  polyglycerol–polyethylene glycol nanoparticles on dermal  drug delivery and biocompatibility.
abstract: Polyglycerol scaffolds and nanoparticles emerged as prominent material for various biomedical applications including topical drug delivery. The impact of slight structural modifications on the nanoparticles' properties, drug delivery potential, and biocompatibility, however, is still not fully understood.Hence, we explored the influence of structural modifications of five structurally related polyglycerol-based nanoparticles (PG-PEG, SK1-SK5) on dermal drug delivery efficiency and biocompatibility. The PG-PEG particles were synthesized via randomly and controlled alkylated chemo-enzymatic approaches resulting in significantly varying particle sizes and interactions with guest molecules. Furthermore, weobserved considerably improved dermal drug delivery with the smallest particles SK4 and SK5 (11 nm and 14 nm) which also correlated with well-defined surface properties achieved by the controlled alkylated synthesis approach. The consistently good biocompatibility for all PG-PEG particles was mainly attributed to the neutral surface charge. No irritation potential, major cytotoxicity or genotoxicity was observed. Nevertheless, slightly better biocompatibility was again seen for the particles characterized by alkyl chain substitution in the core and not on the particle surface.Despite the high structural similarity of the PG-PEG particles, the synthesis and the functionalization significantly influenced particle properties, biocompatibility, and most significantly the drug delivery efficiency.
authors.forename: Sumit
authors.initials: S
authors.lastname: Kumar
authors.forename: Nesrin
authors.initials: N
authors.lastname: Alnasif
authors.forename: Emanuel
authors.initials: E
authors.lastname: Fleige
authors.forename: Indah
authors.initials: I
authors.lastname: Kurniasih
authors.forename: Vivian
authors.initials: V
authors.lastname: Kral
authors.forename: Andrea
authors.initials: A
authors.lastname: Haase
authors.forename: Andreas
authors.initials: A
authors.lastname: Luch
authors.forename: Günther
authors.initials: G
authors.lastname: Weindl
authors.forename: Rainer
authors.initials: R
authors.lastname: Haag
authors.forename: Monika
authors.initials: M
authors.lastname: Schäfer-Korting
authors.forename: Sarah
authors.initials: S
authors.lastname: Hedtrich
mesh_terms: D000818:Animals; D041702:BALB 3T3 Cells; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D065546:Drug Liberation; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D005990:Glycerol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000473:pathology; D051379:Mice; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D010078:Oxazines / Q000008:administration & dosage; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects; D023422:Skin Irritancy Tests; D013552:Swine
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D010078:Oxazines; D004364:Pharmaceutical Preparations; C000599414:polyglycerol-polyethylene glycol; D011092:Polyethylene Glycols; C044808:nile red; D005990:Glycerol