Dataset Information

Surfactant-Triggered Molecular Gate Tested on Different Mesoporous Silica Supports for Gastrointestinal Controlled Delivery.

ABSTRACT: 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.

SUBMITTER: Poyatos-Racionero E

PROVIDER: S-EPMC7407901 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Surfactant-Triggered Molecular Gate Tested on Different Mesoporous Silica Supports for Gastrointestinal Controlled Delivery.

Poyatos-Racionero Elisa E González-Álvarez Isabel I González-Álvarez Marta M Martínez-Máñez Ramón R Marcos M Dolores MD Bernardos Andrea A Aznar Elena E

Nanomaterials (Basel, Switzerland) 20200630 7

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 a ...[more]

PMID: 32630076

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Project description:Melanoma remains the most lethal form of skin cancer and most challenging to treat despite advances in the oncology field. Our work describes the utilization of nanotechnology to target melanoma locally in an attempt to provide an advanced and efficient quality of therapy. Amino-functionalized mesoporous silica nanoparticles (MSN-NH2) were developed in situ through the utilization of anionic surfactant and different volumes of 3-aminopropyltriethoxysilane (APTES) as a co-structure directing agent (CSDA). Prepared particles were characterized for their morphology, particles size, 5-flurouracol (5-FU) and dexamethasone (DEX) loading capacity and release, skin penetration, and cytotoxicity in vitro in HT-144 melanoma cells. Results of transmission electron microscopy (TEM) and nitrogen adsorption-desorption isotherm showed that using different volumes of APTES during the functionalization process had an impact on the internal and external morphology of the particles, as well as particle size. However, changing the volume of APTES did not affect the diameter of formed mesochannels, which was about 4 nm. MSN-NH2 showed a relatively high loading capacity of 5-FU (12.6 ± 5.5) and DEX (44.72 ± 4.21) when using drug: MSN-NH2 ratios of 5:1 for both drugs. The release profile showed that around 83% of 5-FU and 21% of DEX were released over 48 h in pH 7.4. The skin permeability study revealed that enhancement ratio of 5-Fu and DEX using MSN-NH2 were 4.67 and 5.68, respectively, relative to their free drugs counterparts. In addition, the accumulation of drugs in skin layers where melanoma cells usually reside were enhanced approximately 10 times with 5-FU and 5 times with DEX when delivering drugs using MSN-NH2 compared to control. MSN-NH2 alone was nontoxic to melanoma cells when incubated for 48 h in the range of 0 to 468 µg/mL. The combination of 5-FU MSN-NH2 and DEX MSN-NH2 showed significant increase in toxicity compared to their free dug counterparts and exhibited a synergetic effect as well as the ability to circumvent DEX induced 5-FU resistance in melanoma cells.

Project description:Tunable glutathione (GSH)-sensitive hollow mesoporous silica nanoparticles (HMSiO2 NPs) were developed using a structural difference-based selective etching strategy. These organosilica hollow nanoparticles contained disulfide linkages (S-S) in the outer shell which were degraded by GSH. The particles were compared with their nonGSH-sensitive tetraethyl orthosilicate (TEOS) HMSiO2 counterparts in terms of their synthesis method, characterization, doxorubicin (DOX) release profile, and in vitro cytotoxicity in MCF-7 breast cancer cells. Transmission electron microscopy (TEM) of the particles indicated that the fabricated HMSiO2 NPs had an average diameter of 130?±?5?nm. Thermogravimetric analysis (TGA) revealed that GSH-sensitive particles had approximately 5.3% more weight loss than TEOS HMSiO2 NPs. Zeta potential of these redox-responsive particles was -23?±?1?mV at pH?6 in deionized (DI) water. Nitrogen adsorption-desorption isotherm revealed that the surface area of the hollow mesoporous nanoreservoirs was roughly 446?±?6?m2?g-1 and the average diameter of the pores was 2.3?±?0.5?nm. TEM images suggest that the nanoparticles started to lose mass integrity from Day 1. The particles showed a high loading capacity for DOX (8.9?±?0.5%) as a model drug, due to the large voids existing in the hollow structures. Approximately 58% of the incorporated DOX released within 14?days in phosphate buffered saline (PBS) at pH?6 and in the presence of 10?mM of GSH, mimicking intracellular tumor microenvironment while release from TEOS HMSiO2 NPs was only c.a. 18%. The uptake of these hollow nanospheres by MCF-7 cells and RAW 264.7 macrophages was evaluated using TEM and confocal microscopy. The nanospheres were shown to accumulate in the endolysosomal compartments after incubation for 24?h with the maximum uptake of c.a. 2.1?±?0.3% and 5.2?±?0.4%, respectively. Cytotoxicity of the nanospheres was investigated using CCK-8 assay. Results indicate that intact hollow particles (both GSH-sensitive and TEOS HMSiO2 NPs) were nontoxic to MCF-7 cells after incubation for 24?h within the concentration range of 0-1000??g?ml-1. DOX-loaded GSH-sensitive nanospheres containing 6??g?ml-1 of DOX killed c.a. 51% of MCF-7 cells after 24?h while TEOS HMSiO2 NPs killed c.a. 20% with the difference being statistically significant. Finally, cytotoxicity data in RAW 264.7 macrophages and NIH 3?T3 fibroblasts shows that intact GSH-sensitive HMSiO2 NPs did not show any toxic effects on these cells with the concentrations equal or <125??g?ml-1.

Dataset Information

Surfactant-Triggered Molecular Gate Tested on Different Mesoporous Silica Supports for Gastrointestinal Controlled Delivery.

Publications

Surfactant-Triggered Molecular Gate Tested on Different Mesoporous Silica Supports for Gastrointestinal Controlled Delivery.

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