Gated Mesoporous Silica Nanocarriers for a "Two-Step" Targeted System to Colonic Tissue.
Colon targeted drug delivery is highly relevant not only to treat colonic local diseases but also for systemic therapies. Mesoporous silica nanoparticles (MSNs) have been demonstrated as useful systems for controlled drug release given their biocompatibility and the possibility of designing gated systems able to release cargo only upon the presence of certain stimuli. We report herein the preparation of three gated MSNs able to deliver their cargo triggered by different stimuli (redox ambient (S1), enzymatic hydrolysis (S2), and a surfactant or being in contact with cell membrane (S3)) and their performance in solution and in vitro with Caco-2 cells. Safranin O dye was used as a model drug to track cargo fate. Studies of cargo permeability in Caco-2 monolayers demonstrated that intracellular safranin O levels were significantly higher in Caco-2 monolayers when using MSNs compared to those of free dye. Internalization assays indicated that S2 nanoparticles were taken up by cells via endocytosis. S2 nanoparticles were selected for in vivo tests in rats. For in vivo assays, capsules were filled with S2 nanoparticles and coated with Eudragit FS 30 D to target colon. The enteric coated capsule containing the MSNs was able to deliver S2 nanoparticles in colon tissue (first step), and then nanoparticles were able to deliver safranin O inside the colonic cells after the enzymatic stimuli (second step). This resulted in high levels of safranin O in colonic tissue combined with low dye levels in plasma and body tissues. The results suggested that this combination of enzyme-responsive gated MSNs and enteric coated capsules may improve the absorption of drugs in colon to treat local diseases with a reduction of systemic effects.
['González-Alvarez|Marta|M|', 'Coll|Carmen|C|', 'Gonzalez-Alvarez|Isabel|I|', 'Giménez|Cristina|C|', 'Aznar|Elena|E|0000-0003-0361-3876', 'Martínez-Bisbal|M Carmen|MC|', 'Lozoya-Agulló|Isabel|I|', 'Bermejo|Marival|M|0000-0001-5022-0544', 'Martínez-Máñez|Ramón|R|0000-0001-5873-9674', 'Sancenón|Félix|F|']
D000818:Animals D000903:Antibiotics, Antineoplastic D018938:Caco-2 Cells D002470:Cell Survival D003106:Colon D003692:Delayed-Action Preparations D004317:Doxorubicin D004337:Drug Carriers D004339:Drug Compounding D006801:Humans D007413:Intestinal Mucosa D008297:Male D023421:Models, Animal D053758:Nanoparticles D010619:Phenazines D011109:Polymethacrylic Acids D016062:Porosity D051381:Rats D012822:Silicon Dioxide D014018:Tissue Distribution
colon targeting drug delivery mesoporous silica nanoparticles colonic disease gated materials