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Hyaluronic acid/doxorubicin nanoassembly-releasing microspheres for the transarterial chemoembolization of a liver tumor

Lee, Song Yi, Choi, Jin Woo, Lee, Jae-Young, Kim, Dae-Duk, Kim, Hyo-Cheol, Cho, Hyun-Jong·2018·Drug Delivery

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Crossref · 10.1080/10717544.2018.1480673

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Figures

Figure 1. Scheme of the fabrication process of DOX/HACE MS.
Figure 1. Scheme of the fabrication process of DOX/HACE MS.CC BY · PubMed Central
Figure 2. Particle characterization of DOX-loaded MS. (A) Size distribution profiles of DOX MS and DOX/HACE MS. (B) CLSM images of DOX MS and DOX/HACE MS. Depth-dependent cross-sectional images were observed by CLSM. Red fluorescence signal in MS indicates the intraparticle distribution of DOX. The length of the scale bar is 5 μm. (C) Particle characteristics of released DOX/HACE nanoassembly from DOX/HACE MS after incubating for 7 days. Size distribution profile (left) and TEM image (right) are presented. The length of the scale bar in the TEM image is 500 nm.
Figure 2. Particle characterization of DOX-loaded MS. (A) Size distribution profiles of DOX MS and DOX/HACE MS. (B) CLSM images of DOX MS and DOX/HACE MS. Depth-dependent cross-sectional images were observed by CLSM. Red fluorescence signal in MS indicates the intraparticle distribution of DOX. The length of the scale bar is 5 μm. (C) Particle characteristics of released DOX/HACE nanoassembly from DOX/HACE MS after incubating for 7 days. Size distribution profile (left) and TEM image (right) are presented. The length of the scale bar in the TEM image is 500 nm.CC BY · PubMed Central
Figure 3. In vitro degradation test of fabricated MS. DOX MS (A) and DOX/HACE MS (B) were incubated in PBS (pH 7.4) and FBS for 14 days. The morphology of MS was observed by SEM (scale bar = 20 μm). Inset with the yellow boundary indicates the magnified image (scale bar = 2 μm).
Figure 3. In vitro degradation test of fabricated MS. DOX MS (A) and DOX/HACE MS (B) were incubated in PBS (pH 7.4) and FBS for 14 days. The morphology of MS was observed by SEM (scale bar = 20 μm). Inset with the yellow boundary indicates the magnified image (scale bar = 2 μm).CC BY · PubMed Central
Figure 4. Drug release profiles from DOX MS (pH: 7.4) and DOX/HACE MS (pH: 7.4, 6.8, and 5.5). Each point indicates the mean ± SD (n = 3).
Figure 4. Drug release profiles from DOX MS (pH: 7.4) and DOX/HACE MS (pH: 7.4, 6.8, and 5.5). Each point indicates the mean ± SD (n = 3).CC BY · PubMed Central
Figure 5. Cellular accumulation efficiency and in vitro anticancer activities in HepG2 and McA-RH7777 cells. (A) The mean fluorescence intensity values of DOX, measured by flow cytometry, in HepG2 cells and McA-RH7777 cells. Each point indicates the mean ± SD (n = 3). *p < .05, compared with DOX group. #p < .05, compared with DOX MS group. (B) Antiproliferation efficacy, evaluated by MTS-based assay, of DOX-loaded MSs in HepG2 cells and McA-RH7777 cells. Cell viability (%) is presented as the relative percentage based on the control (no treatment) group. Each point indicates the mean ± SD (n = 3). #p < .05, compared with DOX MS group. (C) Apoptotic efficacy of developed MS, measured by Annexin V and PI-based assays, in HepG2 cells and McA-RH7777 cells. UL, LL, LR, and UR indicate upper left, lower left, lower right, and upper right, respectively. Each point indicates the mean ± SD (n = 3). *p < .05, compared with DOX group. #p < .05, compared with DOX MS group.
Figure 5. Cellular accumulation efficiency and in vitro anticancer activities in HepG2 and McA-RH7777 cells. (A) The mean fluorescence intensity values of DOX, measured by flow cytometry, in HepG2 cells and McA-RH7777 cells. Each point indicates the mean ± SD (n = 3). *p < .05, compared with DOX group. #p < .05, compared with DOX MS group. (B) Antiproliferation efficacy, evaluated by MTS-based assay, of DOX-loaded MSs in HepG2 cells and McA-RH7777 cells. Cell viability (%) is presented as the relative percentage based on the control (no treatment) group. Each point indicates the mean ± SD (n = 3). #p < .05, compared with DOX MS group. (C) Apoptotic efficacy of developed MS, measured by Annexin V and PI-based assays, in HepG2 cells and McA-RH7777 cells. UL, LL, LR, and UR indicate upper left, lower left, lower right, and upper right, respectively. Each point indicates the mean ± SD (n = 3). *p < .05, compared with DOX group. #p < .05, compared with DOX MS group.CC BY · PubMed Central
Figure 6. In vivo anticancer activities in the McA-RH7777 tumor-implanted rat model. (A) Serial MR images of liver tumors in control (sham operation), DOX MS, and DOX/HACE MS groups on day 0 (pre-treatment status), 3, and 7 after IA administration. White arrowheads in MR images indicate liver tumor. The length of scale bar in the left side is 1 cm. (B) H&E staining images of dissected liver and tumor, lung, spleen, kidney, and heart in control, DOX MS, and DOX/HACE MS groups. The length of scale bar (shown in the lower right side) in the images of lung, spleen, kidney, and heart is 100 μm.
Figure 6. In vivo anticancer activities in the McA-RH7777 tumor-implanted rat model. (A) Serial MR images of liver tumors in control (sham operation), DOX MS, and DOX/HACE MS groups on day 0 (pre-treatment status), 3, and 7 after IA administration. White arrowheads in MR images indicate liver tumor. The length of scale bar in the left side is 1 cm. (B) H&E staining images of dissected liver and tumor, lung, spleen, kidney, and heart in control, DOX MS, and DOX/HACE MS groups. The length of scale bar (shown in the lower right side) in the images of lung, spleen, kidney, and heart is 100 μm.CC BY · PubMed Central

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Cites

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Metadata

Authors
Lee, S. Y., Choi, J. W., Lee, J.-Y., Kim, D.-D., Kim, H.-C., & Cho, H.-J.
Affiliations
  • College of Pharmacy, Kangwon National University, Chuncheon, Gangwon, Republic of Korea;
  • Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea;
  • College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea;
  • College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea
Venue
Drug Delivery
Published
2018-01-01
Volume
25
Issue
1
Pages
1472-1483
ISSN
  • 1071-7544
  • 1521-0464
Cited by
36
References
3
Language
en
Funders
  • National Research Foundation of Korea (NRF-2017R1E1A1A01074584)
  • Korea Healthcare technology R&D Project
  • Ministry of Health & Welfare, Republic of Korea

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