Mesoporous silica microparticles gated with a bulky azo derivative for the controlled release of dyes/ drugs in colon

[EN] Mesoporous silica microparticles were prepared, loaded with the dye safranin O (M-Saf) or with the drug budesonide (M-Bud) and capped by the grafting of a bulky azo derivative. Cargo release from M-Saf at different pH values (mimicking those found in the gastrointestinal tract) in the absence or presence of sodium dithionite (a reducing agent mimicking azoreductase enzyme present in the colon) was tested. Negligible safranin O release was observed at pH 6.8 and 4.5, whereas a moderate delivery at pH 1.2 was noted and attributed to the hydrolysis of the urea bond that linked the azo derivative onto the external surface of the inorganic scaffold. Moreover, a marked release was observed when sodium dithionite was present and was ascribed to the rupture of the azo bond in the molecular gate. Budesonide release from M-Bud in the presence of sodium dithionite was also assessed by ultraviolet-visible spectroscopy and high performance liquid chromatography measurements. In addition, preliminary in vivo experiments with M-Saf carried out in mice indicated that the chemical integrity of the microparticles remained unaltered in the stomach and the small intestine, and safranin O seemed to be released in the colon.We thank the Spanish Government (projects MAT2015-64139-C4-4-R, MAT2015-64139-C4-2-R and MAT2015-64139-C4-1-R) and Generalitat Valenciana (project PROMETEOII/2014/047 and project AICO/2017/093) for financial support.Ferri, D.; Gaviña, P.; Parra Álvarez, M.; Costero, AM.; El Haskouri, J.; Amorós Del Toro, P.; Merino Sanjuán, V.... (2018). Mesoporous silica microparticles gated with a bulky azo derivative for the controlled release of dyes/ drugs in colon. Royal Society Open Science. 5(8). https://doi.org/10.1098/rsos.180873S58Xu, X.-M., & Zhang, H.-J. (2016). miRNAs as new molecular insights into inflammatory bowel disease: Crucial regulators in autoimmunity and inflammation. 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Smart gated magnetic silica mesoporous particles for targeted colon drug delivery: New approaches for inflammatory bowel diseases treatment

[EN] Magnetic mesoporous silica microparticles were loaded with safranin O (S1) and with hydrocortisone (S2) and the outer surface functionalized with a bulky azo derivative bearing urea moieties. Aqueous suspensions of both solids at pH 7.4 showed negligible payload release whereas a marked delivery was observed in the presence of sodium dithionite due to the rupture of the azo bonds. Besides, a moderate cargo release was observed at acidic pH due to the hydrolysis of the urea bonds that linked the azo derivative onto the external surface of the inorganic scaffolds. In vitro digestion models showed that S1 and S2 microparticles could be used for the controlled release of payload in the reducing colon environment (in which azoreductase enzymes are present). On the other hand, in vivo pharmacokinetic studies in rats showed that safranine O release from S1 microparticles was concentrated in colon. The performance of S2 microparticles for the treatment of colitis in rats (induced by oral administration of a 2,4,6-trinitrobenzenesulfonic acid solution) was tested. The controlled release of hydrocortisone from S2 in the colon of injured rats induced marked reduction in colon/body weight ratio and in clinical activity score. Also, histological studies showed a marked decrease in inflammation followed by intensive regeneration and almost normal mucosal structure of the individuals treated with S2. Besides, the use of a magnetic belt increased the therapeutic performances of S2 due to an enhanced retention time of the particles in the colon.We thank the Spanish Government (projects MAT2015-64139-C4-1-R and AGL2015-70235-C2-2-R (MINECO/FEDER)) and the Generalitat Valenciana (project PROMETEOII/2014/047) for support. AHT thanks to the Spanish MEC for his FPU grant. The authors also thank the Electron Microscopy Service at the Universitat Politecnica de Valencia for support. SCSIE (Universitat de Valencia) is also gratefully acknowledged for all the equipment employed. NMR was registered at the U26 facility of ICTS "NANBIOSIS" at the Universitat de Valencia. The authors thanks Dr. L. A. Villaescusa for his helpful discussion about the 1H NMR analysis of the composition of loaded and functionalized supports.Teruel, AH.; Pérez-Esteve, É.; Gonzalez-Alvarez, I.; Gonzalez -Alvarez, M.; Costero, AM.; Ferri, D.; Parra Álvarez, M.... (2018). Smart gated magnetic silica mesoporous particles for targeted colon drug delivery: New approaches for inflammatory bowel diseases treatment. Journal of Controlled Release. 281:58-69. https://doi.org/10.1016/j.jconrel.2018.05.007S586928

Supplementary Material from Mesoporous silica microparticles gated with a bulky azo derivative for the controlled release of dyes/drugs in colon

Mesoporous silica microparticles were prepared, loaded with the dye safranin O (<b>M-Saf</b>) or with the drug budesonide (<b>M-Bud</b>) and capped by the grafting of a bulky azo derivative. Cargo release from <b>M-Saf</b> at different pH values (mimicking those found in the gastrointestinal tract (GIT)) in the absence or presence of sodium dithionite (a reducing agent mimicking azoreductase enzyme present in the colon) was tested. Negligible safranin O release was observed at pH 6.8 and 4.5, whereas a moderate delivery at pH 1.2 was noted and attributed to the hydrolysis of the urea bond that linked the azo derivative onto the external surface of the inorganic scaffold. Moreover, a marked release was observed when sodium dithionite was present and was ascribed to the rupture of the azo bond in the molecular gate. Budesonide release from <b>M-Bud</b> in the presence of sodium dithionite was also assessed by UV–vis and HPLC measurements. In addition, preliminary <i>in vivo</i> experiments with <b>M-Saf</b> carried out in mice indicated that the chemical integrity of the microparticles remained unaltered in the stomach and the small intestine, and safranin O seemed to be released in the colon