Suchergebnisse

[EN] In recent decades, the versatility of mesoporous silica particles and their relevance to develop controlled release systems have been demonstrated. Within them, gated materials able to modulate payload delivery represent great advantages. However, the role played by the porous matrix in this kind of systems is scarce. In this work, different mesoporous silica materials (MCM-41, MCM-48, SBA-15 and UVM-7) are functionalized with oleic acid as a molecular gate. All systems are fully characterized and their ability to confine the entrapped cargo and release it in the presence of bile salts is validated with release assays and in vitro digestion experiments. The cargo release profile of each synthesized support is studied, paying attention to the inorganic scaffold. Obtained release profiles fit to Korsmeyer-Peppas model, which explains the differences among the studied supports. Based on the results, UVM-7 material was the most appropriate system for duodenal delivery and was tested in an in vivo model of the Wistar rat. Payload confinement and its complete release after gastric emptying is achieved, establishing the possible use of mesoporous silica particles as protection and direct release agents into the duodenum and, hence, demonstrating that these systems could serve as an alternative to the administration methods employed until now. ; This research was funded by the Spanish Government (projects RTI2018-100910-B-C41 and RTI2018-101599-B-C22-AR (MCUI/FEDER, EU)) and the Generalitat Valenciana (project PROMETEO/2018/024 and ACIF/2016/023 grant). ; Poyatos-Racionero, E.; González-Álvarez, I.; González-Álvarez, M.; Martínez-Máñez, R.; Marcos Martínez, MD.; Bernardos Bau, A.; Aznar, E. (2020). Surfactant-Triggered Molecular Gate Tested on Different Mesoporous Silica Supports for Gastrointestinal Controlled Delivery. Nanomaterials. 10(7):1-18. https://doi.org/10.3390/nano10071290 ; S ; 1 ; 18 ; 10 ; 7 ; Pérez-Esteve, É., Ruiz-Rico, M., de la Torre, C., Llorca, E., Sancenón, F., Marcos, M. D., … Barat, J. M. ...

Mesoporous silica microparticles functionalized with lactose for the specific release of essential oil components (EOCs) in the small intestine are presented. In vitro and in vivo intestinal models were applied to validate the microparticles (M41-EOC-L), in which the presence of lactase acts as the triggering stimulus for the controlled release of EOCs. Among the different microdevices prepared (containing thymol, eugenol and cinnamaldehyde), the one loaded with cinnamaldehyde showed the most significant Caco-2 cell viability reduction. On the other hand, interaction of the particles with enterocyte-like monolayers showed a reduction of EOCs permeability when protected into the designed microdevices. Then, a microdevice loaded with cinnamaldehyde was applied in the in vivo model of Wistar rat. The results showed a reduction in cinnamaldehyde plasma levels and an increase in its concentration in the lumen of the gastrointestinal tract (GIT). The absence of payload release in the stomach, the progressive release throughout the intestine and the prolonged stay of the payload in the GIT-lumen increased the bioavailability of the encapsulated compound at the site of the desired action. These innovative results, based on the specific intestinal controlled delivery, suggest that the M41-payload-L could be a potential hybrid microdevice for the protection and administration of bioactive molecules in the small intestine and colon. ; Ministerio de Ciencia, Innovación y Universidades (Spanish Government) )the Agencia Estatal de Investigación (AEI) and European Union (projects RTI2018-100910-B-C41 and RTI2018-101599-B-C22-AR (MCIU/AEI/ FEDER, EU)) ; Ministerio de Universidades (Spanish Government) (BG20/00020, A.B. Beatriz Galindo contract) ; Agencia Estatal de Investigación and European Union through FEDER (Fondo Europeo de Desarrollo Regional, AEI/FEDER EU, project SAF2016-78756) ; Conselleria de Innovación, Universidades, Ciencia y Sociedad Digital, Generalitat Valenciana (project PROMETEO 2018/024 and E.P-R. predoctoral grant ACIF/2016/023)

[EN] Silica mesoporous microparticles loaded with both rhodamine B fluorophore (S1) or hydrocortisone (S2), and capped with an olsalazine derivative, are prepared and fully characterized. Suspensions of Si and S2 in water at an acidic and a neutral pH show negligible dye/drug release, yet a notable delivery took place when the reducing agent sodium dithionite is added because of hydrolysis of an azo bond in the capping ensemble. Additionally, olsalazine fragmentation induced 5-aminosalicylic acid (5-ASA) release. In vitro digestion models show that S1 and S2 solids are suitable systems to specifically release a pharmaceutical agent in the colon. In vivo pharmacokinetic studies in rats show a preferential rhodamine B release from Si in the colon. Moreover, a model of ulcerative colitis is induced in rats by oral administration of 2,4,6-trinitrobenzenesulfonic acid (TNBS) solutions, which was also used to prove the efficacy of S2 for colitis treatment. The specific delivery of hydrocortisone and 5-ASA from S2 material to the colon tissue in injured rats markedly lowers the colon/body weight ratio and the clinical activity score. Histological studies showed a remarkable reduction in inflammation, as well as an intensive regeneration of the affected tissues. ; We thank the Generalitat Valenciana (Project PROMETE02018/024) and the Spanish Government (Projects AGL2015-70235-C2-2-R and MAT2015-64139-C4-1-R (MINECO/FEDER)) for support. A.H.T. thanks the Spanish MEC for his FPU fellowship. The authors also thank the support of the Electron Microscopy Service at the UPV. The SCSIE (of the Universitat de Valencia) is also gratefully acknowledged for all the equipment used. NMR spectra were measured at the U26 facility of ICTS "NANBIOSIS" at the Universitat de Valencia. ; Hernández Teruel, A.; Pérez-Esteve, É.; González-Álvarez, I.; González-Álvarez, M.; Costero Nieto, AM.; Ferri, D.; Gaviña, P. (2019). Double Drug Delivery Using Capped Mesoporous Silica Microparticles for the Effective Treatment of Inflammatory Bowel ...

2418 2429 16 6 ; S ; [EN] Silica mesoporous microparticles loaded with both rhodamine B fluorophore (S1) or hydrocortisone (S2), and capped with an olsalazine derivative, are prepared and fully characterized. Suspensions of Si and S2 in water at an acidic and a neutral pH show negligible dye/drug release, yet a notable delivery took place when the reducing agent sodium dithionite is added because of hydrolysis of an azo bond in the capping ensemble. Additionally, olsalazine fragmentation induced 5-aminosalicylic acid (5-ASA) release. In vitro digestion models show that S1 and S2 solids are suitable systems to specifically release a pharmaceutical agent in the colon. In vivo pharmacokinetic studies in rats show a preferential rhodamine B release from Si in the colon. Moreover, a model of ulcerative colitis is induced in rats by oral administration of 2,4,6-trinitrobenzenesulfonic acid (TNBS) solutions, which was also used to prove the efficacy of S2 for colitis treatment. The specific delivery of hydrocortisone and 5-ASA from S2 material to the colon tissue in injured rats markedly lowers the colon/body weight ratio and the clinical activity score. Histological studies showed a remarkable reduction in inflammation, as well as an intensive regeneration of the affected tissues. We thank the Generalitat Valenciana (Project PROMETE02018/024) and the Spanish Government (Projects AGL2015-70235-C2-2-R and MAT2015-64139-C4-1-R (MINECO/FEDER)) for support. A.H.T. thanks the Spanish MEC for his FPU fellowship. The authors also thank the support of the Electron Microscopy Service at the UPV. The SCSIE (of the Universitat de Valencia) is also gratefully acknowledged for all the equipment used. NMR spectra were measured at the U26 facility of ICTS "NANBIOSIS" at the Universitat de Valencia. Hernández Teruel, A.; Pérez-Esteve, É.; González-Álvarez, I.; González-Álvarez, M.; Costero Nieto, AM.; Ferri, D.; Gaviña, P. (2019). Double Drug Delivery Using Capped Mesoporous Silica Microparticles for the Effective Treatment of ...