title: Diatom silica microparticles for sustained release and permeation enhancement following oral delivery of prednisone and mesalamine.
abstract: Diatoms are porous silica-based materials obtained from single cell photosynthetic algae. Despite low cost, easy purification process, environmentally safe properties, and rapidly increasing potentials for medical applications, the cytotoxicity of diatoms and the effect on drug permeation of oral formulations have not been studied so far. Herein, we have evaluated the potential of diatom silica microparticles (DSMs) for the delivery of mesalamine and prednisone, which are two commonly prescribed drugs for gastrointestinal (GI) diseases. Transmission electron microscopy analysis of the morphological surface changes of Caco-2/HT-29 monolayers and the cell viability data in colon cancer cells (Caco-2, HT-29 and HCT-116) showed very low toxicity of diatoms at concentrations up to 1000 μg/mL. The mesalamine and prednisone release under simulated GI conditions indicated prolonged release of both drugs from the diatoms. Furthermore, drug permeation across Caco-2/HT-29 co-culture monolayers demonstrated that diatoms are capable to enhance the drug permeability. Overall, this study evaluated DSMs' cytotoxicity in colon cancer cells and the effect of DSMs on drug permeability across Caco-2/HT-29 monolayers. Our results demonstrate that DSMs can be considered as a non-cytotoxic biomaterial with high potential to improve the mesalamine and prednisone bioavailability by sustaining the drug release and enhancing drug permeability.
authors.affiliation: Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Zhang
authors.forename: Mohammad-Ali
authors.initials: MA
authors.lastname: Shahbazi
authors.forename: Ermei M
authors.initials: EM
authors.lastname: Mäkilä
authors.forename: Tiago H
authors.initials: TH
authors.lastname: da Silva
authors.forename: Rui L
authors.initials: RL
authors.lastname: Reis
authors.forename: Jarno J
authors.initials: JJ
authors.lastname: Salonen
authors.forename: Jouni T
authors.initials: JT
authors.lastname: Hirvonen
authors.forename: Hélder A
authors.initials: HA
authors.lastname: Santos
mesh_terms: D000284:Administration, Oral; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability / Q000187:drug effects*; D003692:Delayed-Action Preparations; D017377:Diatoms / Q000737:chemistry*; D020895:Enterocytes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D019804:Mesalamine / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D010316:Particle Size; D016062:Porosity; D011241:Prednisone / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D012822:Silicon Dioxide / Q000737:chemistry* / Q000633:toxicity; D055672:Static Electricity
chemical_list: D003692:Delayed-Action Preparations; D019804:Mesalamine; D012822:Silicon Dioxide; D011241:Prednisone
keywords: Cytotoxicity; Diatom; Drug delivery; Mesalamine; Porous silica; Prednisone