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Mesoporous Silica-Bioglass Composite Pellets as Bone Drug Delivery System with Mineralization Potential.

ABSTRACT: For decades, local bone drug delivery systems have been investigated in terms of their application in regenerative medicine. Among them, inorganic polymers based on amorphous silica have been widely explored. In this work, we combined two types of amorphous silica: bioglass and doxycycline-loaded mesoporous silica MCM-41 into the form of spherical granules (pellets) as a bifunctional bone drug delivery system. Both types of silica were obtained in a sol-gel method. The drug adsorption onto the MCM-41 was performed via adsorption from concentrated doxycycline hydrochloride solution. Pellets were obtained on a laboratory scale using the wet granulation-extrusion-spheronization method and investigated in terms of physical properties, drug release, antimicrobial activity against Staphylococcus aureus, mineralization properties in simulated body fluid, and cytotoxicity towards human osteoblasts. The obtained pellets were characterized by satisfactory mechanical properties which eliminated the risk of pellets cracking during further investigations. The biphasic drug release from pellets was observed: burst stage (44% of adsorbed drug released within the first day) followed by prolonged release with zero-order kinetics (estimated time of complete drug release was 19 days) with maintained antimicrobial activity. The progressive biomimetic apatite formation on the surface of the pellets was observed. No cytotoxic effect of pellets towards human osteoblasts was noticed.

SUBMITTER: Szewczyk A

PROVIDER: S-EPMC8124432 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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??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.

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Mesoporous Silica-Bioglass Composite Pellets as Bone Drug Delivery System with Mineralization Potential.

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