6
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      A novel tetrandrine-loaded chitosan microsphere: characterization and in vivo evaluation

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          In this study, novel tetrandrine-loaded chitosan microspheres were prepared by the emulsion cross-linking method. The systems were then characterized for physicochemical properties and in vitro drug release. In addition, the pharmacokinetics and tissue distribution of microspheres were further verified in animal models. Particle-size distribution indicated that the size of microspheres was within the range of 7–15 μm, with a median diameter of 12.4 μm. The drug loading and entrapment efficiency of the formulation were 34.6%±12.5% and 87.3%±9.7% (mean ± SD), respectively. In vitro release showed a typical sustained and long-term drug release behavior. The Higuchi equation was the model that fit best with release data. Maintaining a relatively constant plasma concentration in the long-term drug treatment is an outstanding pharmacokinetic advantage of tetrandrine microspheres in vivo. Moreover, compared with tetrandrine solution, tetrandrine microspheres produced a lower drug concentration in the heart, liver, and kidneys. This indicated that the microspheres used in this study were preferable for targeting lung tissue versus other tissues. No damage to the tissues of the lung was found in histopathological examination.

          Related collections

          Most cited references 28

          • Record: found
          • Abstract: found
          • Article: not found

          Characterization of the initial burst release of a model peptide from poly(D,L-lactide-co-glycolide) microspheres.

          In order to study the mechanism of initial burst release from drug-loaded poly(D,L-lactide-co-glycolide) (PLGA) microspheres, a model peptide, octreotide acetate, was encapsulated in PLGA 50/50 (M(w) approximately 50,000) microspheres using a double emulsion-solvent evaporation method. A simple and accurate continuous monitoring system was developed to obtain a detailed release profile. After different incubation times in the release medium, the morphology and permeability of the microspheres were examined using scanning electron and confocal microscopy (after immersing the microspheres in a fluorescent dye solution for 30 min), respectively. Both the external and internal morphology of the microspheres changed substantially during release of >50% of the peptide over the first 24 h into an acetate buffer, pH 4 at 37 degrees C. After 5 h, a 1-3 microm "skin" layer with decreased porosity was observed forming around the microsphere surface. The density of the "skin" appeared to increase after 24 h with negligible surface pores present, suggesting the formation of a diffusion barrier. Similar morphological changes also occurred at pH 7.4, but more slowly. Correlated with these results, the confocal microscopy studies (at pH 4) showed that the amount of dye penetrated inside the microspheres sharply decreased with time. In summary, over the first 24 h of drug release, a non-porous film forms spontaneously at the surface of octreotide acetate-loaded PLGA microspheres in place of an initially porous surface. These rapid alterations in polymer morphology are correlated with a sharp decline in permeability and the cessation of the initial burst.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            Synergistic antitumour activity of sorafenib in combination with tetrandrine is mediated by reactive oxygen species (ROS)/Akt signaling

             J-J Wan,  T T Liu,  L. Mei (2013)
            Background: Sorafenib is a potent inhibitor against Raf kinase and several receptor tyrosine kinases that has been approved for the clinical treatment of advanced renal and liver cancer. Combining sorafenib with other agents has been shown to improve its antitumour efficacy by not only reducing the toxic side effects but also preventing primary and acquired resistance to sorafenib. We have previously observed that tetrandrine exhibits potent antitumour effects in human hepatocellular carcinoma. In this study, we investigated the synergistic antitumour activity of sorafenib in combination with tetrandrine. Methods: This was a two-part investigation that included the in vitro effects of sorafenib in combination with tetrandrine on cancer cells and the in vivo antitumour efficacy of this drug combination on tumour xenografts in nude mice. Results: Combined treatment showed a good synergistic antitumour effect yet spared nontumourigenic cells. The potential molecular mechanism may be mainly that it activated mitochondrial death pathway and induced caspase-dependent apoptosis in the cancer cells. Accumulation of intracellular reactive oxygen species (ROS) and subsequent activation of Akt may also be involved in apoptosis induction. Conclusion: The antitumour activity of sorafenib plus tetrandrine may be attributed to the induction of the intrinsic apoptosis pathway through ROS/Akt signaling. This finding provides a novel approach that may broaden the clinical application of sorafenib.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Sequential delivery of BMP-2 and IGF-1 using a chitosan gel with gelatin microspheres enhances early osteoblastic differentiation.

              The purpose of this study was to develop and characterize a chitosan gel/gelatin microsphere (MSs) dual delivery system for sequential release of bone morphogenetic protein-2 (BMP-2) and insulin-like growth factor-1 (IGF-1) to enhance osteoblast differentiation in vitro. We made and characterized the delivery system based on its degree of cross-linking, degradation, and release kinetics. We also evaluated the cytotoxicity of the delivery system and the effect of growth factors on cell response using pre-osteoblast W-20-17 mouse bone marrow stromal cells. IGF-1 was first loaded into MSs, and then the IGF-1-containing MSs were encapsulated into the chitosan gel which contained BMP-2. Cross-linking of gelatin with glyoxal via Schiff bases significantly increased thermal stability and decreased the solubility of the MSs, leading to a significant decrease in the initial release of IGF-1. Encapsulation of the MSs into the chitosan gel generated polyelectrolyte complexes by intermolecular interactions, which further affected the release kinetics of IGF-1. This combinational delivery system provided an initial release of BMP-2 followed by a slow and sustained release of IGF-1. Significantly greater alkaline phosphatase activity was found in W-20-17 cells treated with the sequential delivery system compared with other treatments (P<0.05) after a week of culture.
                Bookmark

                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2016
                30 March 2016
                : 10
                : 1291-1298
                Affiliations
                Department of Anesthesia, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China
                Author notes
                Correspondence: Jing Cang, Department of Anesthesia, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Xuhui District, Shanghai 200032, People’s Republic of China, Fax/tel +86 21 6404 1990, Email cjzs2015@ 123456yeah.net
                Article
                dddt-10-1291
                10.2147/DDDT.S103169
                4821377
                27099474
                © 2016 Guo and Cang. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Categories
                Original Research

                Comments

                Comment on this article