The mechanism for increasing the oral bioavailability of poorly water-soluble drugs using uniform mesoporous carbon spheres as a carrier

<p>Uniform mesoporous carbon spheres (UMCS) were used as a carrier to improve the bioavailability of the model drug, celecoxib (CEL). Furthermore, we investigated the mechanism responsible for the improved bioavailability of CEL. The association, adhesion and uptake of UMCS by intestinal epithelial cells were studied by transmission electron microscopy (TEM), fluorescence-activated cell sorting (FACS) and laser confocal scanning microscopy (LCSM). UMCS was found to promote cellular uptake of CEL. Drug transport in Caco-2 cell monolayers proved that UMCS can significantly reduce the rate of drug efflux and improve CEL permeability. The dissolution rate of CEL from drug-loaded samples was markedly improved compared with pure crystalline CEL; moreover, oral bioavailability of CEL loaded into UMCS was also markedly improved compared with that of commercially available capsules. UMCS indicates the advantages and potential of this method to achieve improved oral absorption by increasing the dissolution rate, cellular uptake and permeability of the drug.</p

Designed construction of tween 60@2β-CD self-assembly vesicles as drug delivery carrier for cancer chemotherapy

<p>We report a simple strategy to prepare Tween 60@2β-CD self-assembly vesicles in aqueous solution as a new drug delivery carrier for cancer chemotherapy. The spherical shape of vesicles was confirmed by transmission electron microscopy (TEM) and mean particle sizes were about 33.7 nm, as measured by dynamic light scattering, micro-IR results indicated that the self-assembly vesicles was driven by hydrogen bonding. Hydrophilic doxorubicin (DOX) was successfully loaded into the self-assembly vesicles with drug loading content of 7.85% and loading efficiency of 42%. In addition, an <i>in vitro</i> cytotoxicity study and cellular uptake assays demonstrated that the DOX-loaded Tween 60@2β-CD vesicles markedly enhanced the cellular uptake and cytotoxicity of DOX toward the Hela cells. Furthermore, when used to evaluate the <i>in vivo</i> therapeutic efficacy in mice bearing the breast cell line (4T1), DOX-loaded vesicles exhibited superior inhibition of tumor growth compared with the DOX solutions.</p

Novel Chitosan-Functionalized Spherical Nanosilica Matrix As an Oral Sustained Drug Delivery System for Poorly Water-Soluble Drug Carvedilol

A novel spherical nanosilica matrix (SNM) together with chitosan (CTS) encapsulated SNM (CTS-SNM) was developed in order to investigate the feasibility of using chitosan to regulate drug release rate from porous silica and obtain an oral sustained drug delivery system. To achieve this goal, we synthesized a spherical nanosilica matrix (SNM) and incorporated chitosan chains on the SNM surface. Solvent evaporation method was adopted to load the model drug carvedilol into SNM and CTS-SNM. The physicochemical properties of the drug carriers and drug-loaded composites were systematically studied using scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption, X-ray diffraction (XRD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). The structural changes in CTS-SNM in simulated gastrointestinal fluid as well as the relationships between swelling effect of chitosan and in vitro drug release behaviors were investigated. Pharmacokinetic and bioavailability aspects were also discussed. The results showed that the powerful dispersing effect of SNM and the blocking action due to the swelling of chitosan were the two main factors contributing to the sustained drug release behavior. The swelling effect of chitosan in an acidic environment together with the shrinking effect in a relatively alkaline environment allowed regulation of drug release behavior in simulated gastrointestinal fluid. An in vivo study showed that the bioavailability of CAR was improved 182% compared with that of the commercial capsule when SNM was used as the drug carrier. As for CAR-CTS-SNM, the <i>T</i>_max of CAR was delayed by about 3.4 h and the bioavailability was slightly increased in comparison with the commercial capsule. We believe that SNM and CTS-SNM developed in this study will help increase the use of polymers and inorganic materials in pharmaceutical applications and stimulate the design of oral drug delivery systems for immediate or sustained release of poorly water-soluble drugs

Hybrid Lipid-Capped Mesoporous Silica for Stimuli-Responsive Drug Release and Overcoming Multidrug Resistance

Multidrug resistance (MDR) is known to be a great obstruction to successful chemotherapy, and considerable efforts have been devoted to reverse MDR including designing various functional drug delivery systems. In this study, hybrid lipid-capped mesoporous silica nanoparticles (LTMSNs), aimed toward achieving stimuli-responsive drug release to circumvent MDR, were specially designated for drug delivery. After modifying MSNs with hydrophobic chains through disulfide bond on the surface, lipid molecules composing polymer d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) with molar ratio of 5:1 were subsequently added to self-assemble into a surrounded lipid layer via hydrophobic interaction acting as smart valves to block the pore channels of carrier. The obtained LTMSNs had a narrow size distribution of ca. 190 nm and can be stably dispersed in body fluids, which may ensure a long circulating time and ideal enhanced permeability and retention effect. Doxorubicin (DOX) was chosen as a model drug to be encapsulated into LTMSNs. Results showed that this hybrid lipid-capped mesoporous silica drug delivery system can achieve redox and pH-responsive release of DOX, thereby avoiding the premature leakage of drug before reaching the specific site and releasing DOX within the cancerous cells. Owing to the presence of TPGS-containing lipid layer, LTMSNs–DOX exhibited higher uptake efficiency, cytotoxicity, and increased intracellular accumulation in resistant MCF-7/Adr cells compared with DOX solution, proving to be a promising vehicle to realize intracellular drug release and inhibit drug efflux

Supplemental Material - Association Between Serum Uric Acid and Abdominal Aortic Calcification in Adults Aged 40 to 80 years: A Retrospective Cross-Sectional Study

Supplemental Material for Association Between Serum Uric Acid and Abdominal Aortic Calcification in Adults Aged 40 to 80 years: A Retrospective Cross-Sectional Study by Sheng Hu, Shengyu Qiu, Bingen Wan, Liancheng Ruan, Lingxiao Zhu, Siling Wang, Lang Su, Qiang Guo, Jianjun Xu and Yiping Wei in Journal of Angiology.</p

DataSheet_1_Potential of conserved antigenic sites in development of universal SARS-like coronavirus vaccines.docx

Given pandemic risks of zoonotic SARS-CoV-2 variants and other SARS-like coronaviruses in the future, it is valuable to perform studies on conserved antigenic sites to design universal SARS-like coronavirus vaccines. By using antibodies obtained from convalescent COVID-19 patients, we succeeded in functional comparison of conserved antigenic sites at multiple aspects with each other, and even with SARS-CoV-2 unique antigenic sites, which promotes the cognition of process of humoral immune response to the conserved antigenic sites. The conserved antigenic sites between SARS-CoV-2 and SARS-CoV can effectively induce affinity maturation of cross-binding antibodies, finally resulting in broadly neutralizing antibodies against multiple variants of concern, which provides an important basis for universal vaccine design, however they are subdominant, putatively due to their lower accessibility relative to SARS-CoV-2 unique antigenic sites. Furthermore, we preliminarily design RBDs to improve the immunogenicity of these conserved antigenic sites. Our study focusing on conserved antigenic sites provides insights for promoting the development of universal SARS-like coronavirus vaccines, thereby enhancing our pandemic preparedness.</p