Preparation of an amino hybrid mesoporous silica-based nanotopography protective coating on a titanium implant surface and evaluation of its osteogenic effect / 口腔疾病防治

Objective@#To deposit degradable amino-hybrid mesoporous silica (AHMS) in situ on the surface of titanium nanotube (TNT) and explore its protective effect on nanomorphology and osteogenesis.@*Methods@#TNT and TNT@AHMS were sequentially prepared via an anodizing method: the oil-water two-phase method (experimental group) and the acid-etched titanium method [control group (Ti)]. The parameters for synthesis were explored by changing the silicon source dosage ratio (3∶1, 1∶1, 1∶3); the surface morphology was observed by scanning electron microscope(SEM), hydrophilicity was detected by Water Contact Angle Tester, elemental composition was detected by X-ray photoelectron spectroscopy (XPS); nanoindentation test and ultrasonic oscillator were used to observe the morphological holding effect as mechanical strength of TNT@AHMS in vitro; simulated immersion experiments in vitro was used to observe the degradation behavior of the material. the MC3T3-E1 cell line was used to observe the effect of cell adhesion, proliferation and differentiation on the material; and an SD rat femoral implant model and micro-CT were used to verify the protective effect and osseointegration effect of AHMS on TNT morphology.@*Results@#The morphologies of TNT and TNT@AHMS were successfully prepared, and the silicon source ratio was 1:3. SEM showed that the titanium nanotubes were uniformly covered with AHMS coating, and the mesoporous pore size was about 4 nm. After AHMS was incorporated, the surface of the material was hydrophilic (12.78°), the presence of amino groups (NH2-) was detected, the material was completely degraded within 12 h in vitro, and the active morphology of the TNT was re-exposed with a cumulative silicon release of 10 ppm. Nanoindentation test showed that TNT@AHMS exhibited more ideal surface mechanical strength. SEM revealed that TNT maintains its own morphology under the protection of AHMS, and the TNT group suffered severe exfoliation. In addition, the early adhesion and proliferation rates, ALP activity, and bone volume fraction of cells on the TNT@AHMS surface 4 weeks after implantation were significantly higher than those in the TNT group.@*Conclusion@#By depositing AHMS on the surface of TNT, the nanotopography can be protected. It not only prevents the active base topography from exerting subsequent biological effects but also further endows the material with the ability to promote bone regeneration, laying a foundation for the future development of nanotopography-modified titanium implants.

Preparation and evaluation of sirolimus sustained release tablets based on mesoporous silicon loaded self-microemulsion / 药学学报

Sirolimus self-microemulsion-mesoporous silicon sustained release tablets were prepared in order to improve the dissolution of the insoluble drug sirolimus and reduce its side effects. Firstly, sirolimus self-microemulsion was prepared and cured with mesoporous silicon. Secondly, the suitable excipients were selected according to the appearance, hardness and in vitro release rate. The sustained-release tablets with hydroxypropyl methylcellulose (HPMC) as skeleton material were prepared by powder direct pressing method, and the formulation was optimized by central composite design-response surface method to investigate the drug release in vitro. Finally, the pharmacokinetics was carried out in beagle dogs using the commercial sirolimus tablets as references. The final formulation of sustained-release tablets is as follows: 162 mg of sirolimus self-microemulsion-mesoporous silica (1∶1, w/w), 80 mg of HPMC K4M and 80 mg of carboxymethyl starch sodium, the microcrystalline cellulose is 168 mg. The results of in vitro release test showed that the self-made sustained-release tablets released slowly within 12 h, which conformed to the Ritger-Peppas model. The in vivo test results showed that compared with the commercial sirolimus tablets, the Cmax of the sustained-release tablets decreased by 49.47%, the Tmax of the sustained-release tablets was prolonged by 5.1 times, and the relative bioavailability was 105.81%. Sirolimus self-microemulsion-mesoporous silicon sustained-release tablets have good sustained-release effects in vitro and in vivo, which provides a reference for the solubilization of other insoluble drugs and the research and development of sustained-release preparations. Animal experiments and welfare processes were reviewed and approved by the Animal Ethics Committee of the 900TH Hospital of the Joint Logistics support Force.

Delivery of miR-375 and doxorubicin hydrochloride by lipid bilayer coated hollow mesoporous silica nanoparticles for liver cancer therapy / 药学学报

This study was designed to prepare a novel lipid bilayer coated hollow mesoporous silica nanocarrier for co-delivery of gene drugs and chemotherapeutic drugs to enhance the inhibitory activity of antitumor drugs in hepatoma cells. Hollow mesoporous silica was synthesized by modified StÖber method. Lipid-fusion principle was used to prepare lipid-hollow co-loaded doxorubicin (DOX) and miR-375 (LHMSN-DOX/miR-375). Meanwhile, the morphology, particle size, surface potential, drug loading and release were characterized in vitro. The inhibition of cell proliferation, cell migration and invasion was then evaluated. The results indicated that the core-shell structure of LHMSN-DOX/miR-375 was clear with an intact outer lipid membrane and an ordered internal HMSN mesoporous structure. The drug release amount was pH responsive while the drug was rapidly released under simulated intracellular acidic conditions relative to normal physiological environment. Compared with free DOX, LHMSN-DOX/miR-375 can deliver DOX and miR-375 to liver cancer cells and inhibit the proliferation, migration and invasion of cells more effectively.