title: Microfluidic templated mesoporous silicon-solid lipid microcomposites for sustained drug delivery.
abstract: A major challenge for a drug-delivery system is to engineer stable drug carriers with excellent biocompatibility, monodisperse size, and controllable release profiles. In this study, we used a microfluidic technique to encapsulate thermally hydrocarbonized porous silicon (THCPSi) microparticles within solid lipid microparticles (SLMs) to overcome the drawbacks accompanied by THCPSi microparticles. Formulation and process factors, such as lipid matrixes, organic solvents, emulsifiers, and methods to evaporate the organic solvents, were all evaluated and optimized to prepare monodisperse stable SLMs. FTIR analysis together with confocal images showed the clear deposition of THCPSi microparticles inside the monodisperse SLM matrix. The formation of monodisperse THCPSi-solid lipid microcomposites (THCPSi-SLMCs) not only altered the surface hydrophobicity and morphology of THCPSi microparticles but also remarkably enhanced their cytocompatibility with intestinal (Caco-2 and HT-29) cancer cells. Regardless of the solubility of the loaded therapeutics (aqueous insoluble, fenofibrate and furosemide; aqueous soluble, methotrexate and ranitidine) and the pH values of the release media (1.2, 5.0, and 7.4), the time for the release of 50% of the payloads from THCPSi-SLMC was at least 1.3 times longer than that from the THCPSi microparticles. The sustained release of both water-soluble and -insoluble drugs together with a reduced burst-release effect from monodisperse THCPSi-SLMC was achieved, indicating the successful encapsulation of THCPSi microparticles into the SLM matrix. The fabricated THCPSi-SLMCs exhibited monodisperse spherical morphology, enhanced cytocompatibility, and prolonged both water-soluble and -insoluble drug release, which makes it an attractive controllable drug-delivery platform.
authors.affiliation: Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki , FI-00014 Helsinki, Finland.
authors.forename: Dongfei
authors.initials: D
authors.lastname: Liu
authors.forename: Bárbara
authors.initials: B
authors.lastname: Herranz-Blanco
authors.forename: Ermei
authors.initials: E
authors.lastname: Mäkilä
authors.forename: Laura R
authors.initials: LR
authors.lastname: Arriaga
authors.forename: Sabiruddin
authors.initials: S
authors.lastname: Mirza
authors.forename: David A
authors.initials: DA
authors.lastname: Weitz
authors.forename: Niklas
authors.initials: N
authors.lastname: Sandler
authors.forename: Jarno
authors.initials: J
authors.lastname: Salonen
authors.forename: Jouni
authors.initials: J
authors.lastname: Hirvonen
authors.forename: Hélder A
authors.initials: HA
authors.lastname: Santos
mesh_terms: D018938:Caco-2 Cells; D016503:Drug Delivery Systems; D011345:Fenofibrate / Q000737:chemistry* / Q000494:pharmacology; D005665:Furosemide / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D000960:Hypolipidemic Agents / Q000737:chemistry* / Q000494:pharmacology; D008055:Lipids / Q000737:chemistry* / Q000494:pharmacology; D046210:Microfluidic Analytical Techniques; D053761:Nanocomposites / Q000737:chemistry*; D016062:Porosity; D012825:Silicon / Q000737:chemistry* / Q000494:pharmacology; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000960:Hypolipidemic Agents; D008055:Lipids; D049994:Sodium Potassium Chloride Symporter Inhibitors; D005665:Furosemide; D011345:Fenofibrate; D012825:Silicon