title: Coherent anti-Stokes Raman scattering microscopy driving the future of loaded mesoporous silica imaging.
abstract: This study reports the use of variants of coherent anti-Stokes Raman scattering (CARS) microscopy as a novel method for improved physicochemical characterization of drug-loaded silica particles. Ordered mesoporous silica is a biomaterial that can be loaded to carry a number of biochemicals, including poorly water-soluble drugs, by allowing the incorporation of drug into nanometer-sized pores. In this work, the loading of two poorly water-soluble model drugs, itraconazole and griseofulvin, in MCM-41 silica microparticles is characterized qualitatively, using the novel approach of CARS microscopy, which has advantages over other analytical approaches used to date and is non-destructive, rapid, label free, confocal and has chemical and physical specificity. The study investigated the effect of two solvent-based loading methods, namely immersion and rotary evaporation, and microparticle size on the three-dimensional (3-D) distribution of the two loaded drugs. Additionally, hyperspectral CARS microscopy was used to confirm the amorphous nature of the loaded drugs. Z-stacked CARS microscopy suggested that the drug, but not the loading method or particle size range, affected 3-D drug distribution. Hyperspectral CARS confirmed that the drug loaded in the MCM-41 silica microparticles was in an amorphous form. The results show that CARS microscopy and hyperspectral CARS microscopy can be used to provide further insights into the structural nature of loaded mesoporous silica microparticles as biomaterials.
authors: Optical Sciences Group, MESA+ Institute of Nanotechnology, University of Twente, PO Box 217, 7500AE Enschede, The Netherlands.
authors: Andrew L
authors: AL
authors: Fussell
authors: School of Pharmacy, University of Otago, 9054 Dunedin, New Zealand; Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
authors: Pei Ting
authors: PT
authors: Mah
authors: Optical Sciences Group, MESA+ Institute of Nanotechnology, University of Twente, PO Box 217, 7500AE Enschede, The Netherlands. Electronic address: H.L.Offerhaus@utwente.nl.
authors: Herman
authors: H
authors: Offerhaus
authors: Laboratory of Industrial Physics, Department of Physics and Astronomy, University of Turku, FI-20014 Turku, Finland.
authors: Sanna-Mari
authors: SM
authors: Niemi
authors: Laboratory of Industrial Physics, Department of Physics and Astronomy, University of Turku, FI-20014 Turku, Finland.
authors: Jarno
authors: J
authors: Salonen
authors: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
authors: Hélder A
authors: HA
authors: Santos
authors: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
authors: Clare
authors: C
authors: Strachan
mesh_terms: D006118:Griseofulvin / Q000494:pharmacology; D021621:Imaging, Three-Dimensional; D017964:Itraconazole / Q000494:pharmacology; D008853:Microscopy / Q000379:methods*; D008855:Microscopy, Electron, Scanning; D004364:Pharmaceutical Preparations; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry*; D013059:Spectrum Analysis, Raman / Q000379:methods*; D013818:Thermogravimetry
chemical_list: C509968:MCM-41; D004364:Pharmaceutical Preparations; D017964:Itraconazole; D006118:Griseofulvin; D012822:Silicon Dioxide
keywords: Coherent anti-Stokes Raman scattering; Mesoporous silica; Microparticles; Microscopy; Poorly water-soluble drugs