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Mesoporous silica-based hybrid materials for bone-specific drug delivery.

ABSTRACT: A mesoporous silica-based drug delivery device potentially useful for bone-specific drug delivery has been designed, developed and characterized starting from MSU-type mesoporous silica. The proposed system consists of a mesoporous silica nanoparticles (MSN) based vehicle, presenting alendronate as a targeting functionality for bone tissue while ibuprofen is used as a model molecule for the drugs to be delivered. The particles are functionalized on the external surface using a propionitrile derivative that is successively hydrolyzed to a carboxylic group. Alendronate, one of the most used member of the diphosphonate drug class, is electrostatically bonded to the external carboxyl functionalities of mesoporous silica. The obtained material has been characterized by powder X-ray diffraction, N₂ adsorption-desorption porosimetry, UV-vis spectrophotometry, FT-IR spectrometry and MAS-NMR ¹³C and ²⁹Si. Hydroxyapatite, which simulates the bone matrix, has been synthesized with the aim of testing the targeting activity of the obtained device. In a separate test, the MSNs have been loaded with ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), and its release has been determined under neutral conditions by HPLC. Moreover, biological tests were carried out. The tested devices did not show any toxicity towards normal cells, confirming their high biocompatibility and the lack of off-target effects.

SUBMITTER: Pasqua L

PROVIDER: S-EPMC9417532 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Mesoporous silica-based hybrid materials for bone-specific drug delivery.

Pasqua Luigi L De Napoli Ilaria Ester IE De Santo Marzia M Greco Marianna M Catizzone Enrico E Lombardo Domenico D Montera Gabriella G Comandè Alessandra A Nigro Alessandra A Morelli Catia C Leggio Antonella A

Nanoscale advances 20190703 8

A mesoporous silica-based drug delivery device potentially useful for bone-specific drug delivery has been designed, developed and characterized starting from MSU-type mesoporous silica. The proposed system consists of a mesoporous silica nanoparticles (MSN) based vehicle, presenting alendronate as a targeting functionality for bone tissue while ibuprofen is used as a model molecule for the drugs to be delivered. The particles are functionalized on the external surface using a propionitrile deri ...[more]

PMID: 36133588

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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 μg ml-1. DOX-loaded GSH-sensitive nanospheres containing 6 μg 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 μg ml-1.

Dataset Information

Mesoporous silica-based hybrid materials for bone-specific drug delivery.

Publications

Mesoporous silica-based hybrid materials for bone-specific drug delivery.

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