title: Production of polymeric micelles by microfluidic technology for combined drug delivery: application to osteogenic differentiation of human periodontal ligament mesenchymal stem cells (hPDLSCs).
abstract: The current paper reports the production of polymeric micelles (PMs), based on pluronic block-copolymers, as drug carriers, precisely controlling the cellular delivery of drugs with various physico-chemical characteristics. PMs were produced with a microfluidic platform to exploit further control on the size characteristic of the PMs. PMs were designed for the co-delivery of dexamethasone (Dex) and ascorbyl-palmitate (AP) to in vitro cultured human periodontal ligament mesenchymal stem cells (hPDLSCs) for the combined induction of osteogenic differentiation. Mixtures of block-copolymers and drugs in organic, water miscible solvent, were conveniently converted in PMs within microfluidic channel leveraging the fast mixing at the microscale. Our results demonstrated that the drugs can be efficiently co-encapsulated in PMs and that different production parameters can be adjusted in order to modulate the PM characteristics. The comparative analysis of PM produced by microfluidic and conventional procedures confirmed that the use of microfluidics platforms allowed the production of PMs in a robust manner with improved controllability, reproducibility, smaller size and polydispersity. Finally, the analysis of the effect of PMs, containing Dex and AP, on the osteogenic differentiation of hPDLSCs is reported. The data demonstrated the effectiveness and safety of PM treatment on hPDLSC. In conclusion, this report indicates that microfluidic approach represents an innovative and useful method for PM controlled preparation, warrant further evaluation as general methodology for the production of colloidal systems for the simultaneous drug delivery.
authors.affiliation: Engineering Sciences, Faculty of Engineering and the Environment, University of Southampton, University Road, Southampton SO17 1BJ, UK.
authors.forename: L
authors.initials: L
authors.lastname: Capretto
authors.forename: S
authors.initials: S
authors.lastname: Mazzitelli
authors.forename: G
authors.initials: G
authors.lastname: Colombo
authors.forename: R
authors.initials: R
authors.lastname: Piva
authors.forename: L
authors.initials: L
authors.lastname: Penolazzi
authors.forename: R
authors.initials: R
authors.lastname: Vecchiatini
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: C
authors.initials: C
authors.lastname: Nastruzzi
mesh_terms: D001205:Ascorbic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology; D004337:Drug Carriers / Q000008:administration & dosage / Q000494:pharmacology; D004339:Drug Compounding / Q000379:methods; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000502:physiology; D008823:Micelles; D044085:Microfluidics / Q000295:instrumentation / Q000379:methods*; D010012:Osteogenesis / Q000187:drug effects*; D010316:Particle Size; D010513:Periodontal Ligament / Q000166:cytology; D011108:Polymers / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; D003907:Dexamethasone; D001205:Ascorbic Acid; C031226:6-O-palmitoylascorbic acid