In vitro release and in vitro–in vivo correlation for silybin meglumine incorporated into hollow-type mesoporous silica nanoparticles

Abstract

Background:The purpose of this study was to develop a sustained drug-release model for water-soluble drugs using silica nanoparticles. Methods: Hollow-type mesoporous silica nanoparticles (HMSNs) were prepared using Na 2 CO 3 solution as the dissolution medium for the first time. The water-soluble compound, silybin meglumine, was used as the model drug. The Wagner-Nelson method was used to calculate the in vivo absorption fraction. Results:The results of transmission electron microscopy and nitrogen adsorption revealed that the empty HMSNs had uniformly distributed particles of size 50-100 nm, a spherical appearance, a large specific surface area (385.89 ± 1.12 m 2 /g), and ultralow mean pore size (2.74 nm). The highly porous structure allowed a large drug-loading rate (58.91% ± 0.39%). In 0.08 M Na 2 CO 3 solution, silybin meglumine-loaded HMSNs could achieve highly efficacious and long-term sustained release for 72 hours in vitro. The results of in vitro-in vivo correlation revealed that HMSNs in 0.08 M Na 2 CO 3 solution had a correlation coefficient R 2 value of 0.9931, while those of artificial gastric juice and artificial intestinal juice were only 0.9287 and 0.7689, respectively. Conclusion:The findings of in vitro-in vivo correlation indicate that HMSNs together with Na 2 CO 3 solution could achieve an excellent linear relationship between in vitro dissolution and in vivo absorption for 72 hours, leading to a promising model for sustained release of watersoluble drugs.

IGF-1R/epithelial-to-mesenchymal transition (EMT) crosstalk suppresses the erlotinib-sensitizing effect of EGFR exon 19 deletion mutations

“…Silibinin has been shown to reduce IGF-1R phosphorylation, indicating an inhibitory effect on the IGF-1R-mediated signaling pathway in cancer cells5556. Through using a milk thistle extract rich in silybin meglumine, a commercially used water-soluble form of silibinin57, we are currently testing whether the anti-IGF-1R/EMT activity of silibinin can translate into the reversal of acquired resistance to EGFR TKIs in animal models. A dual targeting of IGF-1R and EMT might be crucial to prevent and/or circumvent acquired resistance to erlotinib in EGFR-mutated cells because, although early studies by Morgillo et al58 provided evidence that erlotinib induces heterodimerization of EGFR/IGF-1R, we failed to observe either co-localization of the phospho-active forms of EGFR and IGF-1R or changes in the phosphorylation status of EGFR upon pharmacological blockade of IGF-1R in EMT-like, erlotinib-refractory pooled populations (data not shown).…”

Formulation Strategies for Enhancing the Bioavailability of Silymarin: The State of the Art

“…Moreover, they can exhibit excellent biocompatibility, biodegradation, in vivo stability, low cytotoxicity and nonimmunogenic profiles, thereby making these nanovectors an ideal candidate for oral and parenteral drug delivery [138]. One of the first applications of these inorganic nanomaterials as carriers of a water-soluble form of SIL (molecular complex with the amino-sugar meglumine), was provided by Cao et al by engineering hollow-type mesoporous silica NPs (HMSNs) [139]. They were prepared in a W/O microemulsion formulated with nonylphenol 10 as surfactant and subjected to ultrasound irradiation to generate micropores and microchannels within the silica spheres.…”

Fabrication of Progesterone-Loaded Nanofibers for the Drug Delivery Applications in Bovine

“…In literature [ 2 ], reported functional electrospun nanofibrous composite structures can also be produced by incorporating functional additives in the fiber matrix or on the fiber surface. The development of nanostructured systems for the delivery and sustained release of molecules towards specific targets represents a frontier area of nanoscience and nanotechnology, with the possibility of contributing substantially to advances in animal reproduction [ 3 ]. Improving delivery techniques that minimize toxicity of drug has a significant effect on its efficacy.…”