ABSTRACT
Fibrosis is one of the key factors that lead to the immune exclusion of solid tumors. Although degradation of fiber is a promising strategy, its application was still bottlenecked by the side effects of causing metastasis, resulting in the failure of immunotherapy. Here, we developed an antimetastatic polymer (HPA) for the delivery of chemo-drug and antifibrotic siPAI-1 to form the nano-permeator. Nano-permeator shrank after protonation and deeply penetrated into the tumor core to down-regulate the expression of PAI-1 for antifibrosis, and further promoted the sustained infiltration and activation of T cells for killing tumor cells. Moreover, metastasis after fiber elimination was prevented by multivalent CXCR4 antagonistic HPA to reduce the attraction of CXCL12 secreted by distant organs. The administration of stroma-alleviated immunotherapy increased the infiltration of CD8+ T cells to 52.5% in tumor tissues, inhibiting nearly 90% metastasis by HPA in distant organs. The nano-permeator reveals the mechanism and correlation between antifibrosis and antimetastasis and was believed to be the optimizing immunotherapy for solid fibrotic tumors.
ABSTRACT
@#With the development of biomimetic technology, more and more in vitro models are used to simulate human physiological and pathological processes.These in vitro models can solve some scientific problems, such as studying drug effects in real-timely and visually.As an in vitro model, organ-on-a-chip provides novel means and methods for basic and applied science.The vascularized organ-on-a-chip, as a special kind of organ-on-a-chip, can better simulate the structure and function of human blood vessels.In this review, we summarized the structure and function of different vascularized organ-on-a-chip, analyzed the application of vascularized organ-on-a-chip in simulating physiological and pathological processes, and discussed the advantages and problems to be solved of vascularized organ-on-a-chip as a new in vitro model.Finally, the application of vascularized organ-on-a-chip is proposed.
ABSTRACT
@#Polyethylene glycol (PEG) of different lengths were prepared to investigate their effects on oral absorption of nanostructured lipid carrier (NLCs).Three kinds of PEG-modified NLCs with different chain lengths, including polyethylene glycol (100) monostearate (S100), polyethylene glycol (55) monostearate (S55), polyethylene glycol (40) monostearate (S40), were prepared by film dispersion method.Coumarin 6 was chosen as a fluorescent probe to characterize the physicochemical properties of NLCs with different lengths.Meanwhile, the stability of NLCs in simulate buffer, the release behavior, cytotoxicity of NLCs, the uptake kinetics and cellular uptake mechanisms were evaluated. This work demonstrated that the thickness of the hydrated layer increased with the increase of PEG length. Of note, S100-modified NLCs (pNLC-EG100) exhibited higher cellular uptake efficiency compared with other formulations. Thus, S100 was optimized as the best molecular weight for PEG-modified NLCs on oral drug delivery system.
ABSTRACT
@#With the rapid development of nanotechnology, accurate personalized treatments for tumor have attracted more attention to increase the therapeutic effects and reduce the side effects. The emerging theranostic systems incorporating different therapeutic and diagnostic imaging capabilities have become a new research hotspot. Magnetic iron oxide nanoparticles(IONP)have been widely used in theranostic systems due to their unique imaging properties, stable thermal performance, excellent biocompatibility and admirable surface modifiability. In this review, we analyzed the advantages of IONP in the diagnosis and the treatment of tumor, and detailedly introduced the relevant strategies and latest research progress, including magnetic resonance imaging(MRI), photothermal therapy, magnetic hyperthermia, and magnetic targeted drug delivery, etc. Finally, the potential application of IONP in the clinical tumor theranostics was proposed.
ABSTRACT
@#Abstract The indomethacin-nicotinamide cocrystal was prepared by hot melt extrusion(HME)to improve the dissolution of indomethacin in vitro. The optimum preparation conditions were investigated using temperature and rotate speed as variables. Thermogravimetric analysis(TGA), determination of content and determination of related substances were performed to evaluate the thermal stability of indomethacin during the process. Cocrystal was also prepared by solution crystallization from acetonitrile. The products obtained by the two methods were characterized by differential scanning calorimetry(DSC), Fourier transform infrared(FTIR)and powder X-ray diffraction(PXRD). The solubility and dissolution advantages of cocrystal were evaluated. The results showed that the HME method could successfully prepare the indomethacin-nicotinamide cocrystal at 115 °C and eutectic mixture was formed during the process. The cocrystal significantly improved the solubility and dissolution of indomethacin in deionized water, with pH 5. 5 and pH 6. 8 phosphate buffer. The preparation of poorly soluble drug cocrystal by HME can significantly improve its solubility, providing new idea for the development of poorly soluble drugs and HME technology.
ABSTRACT
@#Wax matrix tablets is a special pharmaceutical controlled release preparation. However, it has not yet been fully studied and applied. In this article, the progress in carriers and techniques for the preparation of wax matrix tablets in recent years was reviewed. Analysis and comparison of their advantages and disadvantages can help to promote the application of wax matrix tablets in the future.
ABSTRACT
@#To construct nanostructured lipid carriers(NLCs)with different particle sizes but the same other physicochemical properties, central composite design was adopted. Coumarin-6(C-6)was selected as the model drug due to its high lipophilicity and high fluorescence intensity. Physicochemical properties of NLCs with 100 nm, 200 nm and 300 nm in particle size could remain stable during certain time in K-R solution and PBS. Release experiments in vitro showed that cumulative release of C-6 in NLCs was less than 7% after 24 h. The MTT assay indicated that both blank NLCs and C-6 loaded NLCs showed low toxicity. To confirm the integrity of NLCs in gastrointestinal tract, DiR-loaded NLCs were prepared and the distribution in vivo was monitored by fluorescence imaging. After 6 h oral administration, intact DiR-loaded NLCs could stiu be found, suggesting that NLCs could be used to characterize the uptake in gastrointestinal tract.
ABSTRACT
Aim:To prepare vinblastine-loaded PCL-PEG_(6000)-PCL nanoparticles,and to study their physicochemi-cal properties and in vitro antitumor activity.Methods: PCL-PEG_(6000)-PCL triblock copolymer was prepared by ring-opening polymerization,and vinblastine-loaded PCL-PEG_(6000)-PCL nanoparticles was prepared by coprecipita-tion.The morphous,particle size,polydisperse index,particle yield,the drag-loading content,the encapsulation ef-ficiency and in vitro release rate of these vinblastine-loaded nanoparticles were determined.The cytotoxicity of vinblastine-loaded nanoparticles to K562/A02 leukimia cell line was determined by MTT assay.Results: It was found using transmission electron microscopy(TEM)that the nanoparticles exhibited a spherical shape with core-shell structure.The particle sizes of the nanoparticles obtained by dynamic light scattering were(185 ± 2.7)nm.The drug loading content and the encapsulation efficiency were determined to be 28.83% and 86.52%,re-spectively.In vitro release study revealed that more than 70% of accumulative release of entrapped vinblastine was reached in 9 hr and that nearly complete release was achieved in 24 hr.The inhibition of vinblastine-loaded nanoparticles to K562/A02 cell line was significantly increased as compared with that of the same dose of sulfate vinblastine solution.Conclusions: PCL-PEG-PCL nanoparticles could be used as a carrier of vinblastine,and the prepared nanoparticles exhibited a spherical shape,high encapsulation efficiency,relevant stablity and sustained-release properties.The eytotoxicity of vinblastine to K562/A02 cell line was significantly increased when it was encapsulated in PCL-PEG-PCL nanoparticles.
ABSTRACT
To study the multidrug resistance activity of 1-alkyl-2-acetyl-1, 2, 3, 4-tetrahydroisoquinoline derivatives. Methods: A series of novel tetrahydroisoquinoline derivatives bearing at C-1 position a carbon chain derived from fatty acids were prepared through the Bischler-Napieralski cyclization reaction. Their multidrug resistance (MDR) reversal cancerous multidrug resistance activities were evaluated against K562 and K562/DOX cell lines in vitro by MTT assay with verapamil as a control. Results and Conclusion: The structures of these tetrahydroisoquinolines were confirmed by extensive spectroscopic methods(1H NMR, MS, IR and elemental ana-lyses). MDR results showed that compounds 7 and 10 exhibited moderate reversal activities, and were slightly less potent than those of verapamil against K562 cell line. It is believed that compounds 7 and 10 have MDR activity.