Advertisement

Biomedical Microdevices

, 21:78 | Cite as

20(S)-Ginsenoside Rg3-loaded electrospun membranes to prevent postoperative peritoneal adhesion

  • Renna Qiu
  • Jian Li
  • Denghua Sun
  • Hongjun LiEmail author
  • Feng QianEmail author
  • Lizhe WangEmail author
Article
  • 8 Downloads

Abstract

Postoperative peritoneal adhesions are one of the most common surgical complications. In this study, we developed a 20(S)-ginsenoside Rg3-loaded methoxy poly (ethylene glycol)-block-poly(L-lactide-co-glycolide) (mPEG-b-PLGA) electrospun membrane (PEM/Rg3) that could not only serve as a physical barrier, but also as a drug delivery system that releases 20(S)-ginsenoside Rg3 constantly to prevent postoperative peritoneal adhesions. The characteristics of PEM/Rg3, including scanning electron microscopy, water contact angle, and mechanical analyses, were assessed. Degradation and drug release assays of PEM/Rg3 were performed. The anti-adhesion efficacy of PEM/Rg3 was evaluated in an abdomen-cecum mouse model. The adhesion scores, adhesion areas, hematoxylin and eosin (H&E) staining, immunofluorescence, and western blotting were assessed. The 20(S)-ginsenoside Rg3 loaded mPEG-b-PLGA electrospun fibers were successfully fabricated. The fibers were smooth, with no obvious drug crystals. PEM/Rg3 membranes were biodegradable and could be degraded gradually to release 20(S)-Ginsenoside Rg3 constantly from the membranes. The animal study showed that PEM/Rg3 exhibited an excellent adhesion prevention ability when compared with the control group, the PEM group, and polylactic acid (PLA) commercial membrane (Surgiwrap™) group. Immunofluorescence and western blotting studies showed that PEM/Rg3 inhibited the expressions of interleukin 1 (IL-1), interleukin 6 (IL-6), and reactive oxygen species modulator-1 (ROMO1). The 20(S)-ginsenoside Rg3-loaded mPEG-b-PLGA electrospun membranes exhibited satisfactory anti-adhesion efficacy by inhibiting inflammatory responses and oxidative stress. This composite represents a promising strategy to prevent postoperative peritoneal adhesions.

Keywords

Electrospun membrane 20(S)-ginsenoside Rg3 Anti-adhesion Peritoneal adhesions 

Notes

Acknowledgments

We thank Elixigen Corporation (Huntington Beach, California, USA) for helping in proofreading and editing the English of the final manuscript.

Compliance with ethical standards

Declaration of interest

The authors report no declarations of interest.

References

  1. K.M. Braun, M.P. Diamond, The biology of adhesion formation in the peritoneal cavity. Semin. Pediatr. Surg. 23(6), 336–343 (2014)CrossRefGoogle Scholar
  2. J. Buschmann, M. Calcagni, G.M. Burgisser, E. Bonavoglia, P. Neuenschwander, V. Milleret, et al., Synthesis, characterization and histomorphometric analysis of cellular response to a new elastic DegraPol(R) polymer for rabbit Achilles tendon rupture repair. J. Tissue Eng. Regen. Med. 9(5), 584–594 (2015)CrossRefGoogle Scholar
  3. J. Cashman, H.M. Burt, C. Springate, J. Gleave, J.K. Jackson, Camptothecin-loaded films for the prevention of postsurgical adhesions. Inflamm. Res. 53(8), 355–362 (2004)CrossRefGoogle Scholar
  4. L. Cheng, X. Sun, C. Hu, R. Jin, B. Sun, Y. Shi, et al., In vivo early intervention and the therapeutic effects of 20(s)-ginsenoside rg3 on hypertrophic scar formation. PLoS One 9(12), e113640 (2014)CrossRefGoogle Scholar
  5. M.Y. Chung, S.K. Jung, H.J. Lee, D.H. Shon, H.K. Kim, Ethanol extract of Sarcodon asparatus mitigates inflammatory responses in lipopolysaccharide-challenged mice and murine macrophages. J. Med. Food 18(11), 1198–1206 (2015)CrossRefGoogle Scholar
  6. S. Jiang, X. Zhao, S. Chen, G. Pan, J. Song, N. He, et al., Down-regulating ERK1/2 and SMAD2/3 phosphorylation by physical barrier of celecoxib-loaded electrospun fibrous membranes prevents tendon adhesions. Biomaterials 35(37), 9920–9929 (2014)CrossRefGoogle Scholar
  7. S. Jiang, H. Yan, D. Fan, J. Song, C. Fan, Multi-layer electrospun membrane mimicking tendon sheath for prevention of tendon adhesions. Int. J. Mol. Sci. 16(4), 6932–6944 (2015)CrossRefGoogle Scholar
  8. H. Kang, Y.G. Hwang, T.G. Lee, C.R. Jin, C.H. Cho, H.Y. Jeong, et al., Use of gold nanoparticle fertilizer enhances the Ginsenoside contents and anti-inflammatory effects of red ginseng. J. Microbiol. Biotechnol. 26(10), 1668–1674 (2016)CrossRefGoogle Scholar
  9. M.V. Karaaltin, B. Ozalp, M. Dadaci, A. Kayikcioglu, A. Kecik, F. Oner, The effects of 5-fluorouracil on flexor tendon healing by using a biodegradable gelatin, slow releasing system: Experimental study in a hen model. J. Hand Surg. Eur. Vol. 38(6), 651–657 (2013)CrossRefGoogle Scholar
  10. G. Kayaoglu, H. Erten, T. Alaçam, D. Ørstavik, Short-term antibacterial activity of root canal sealers towards enterococcus faecalis. Int. Endod. J. 38(7), 483–488 (2005)CrossRefGoogle Scholar
  11. D.K. Kim, K.J. Kweon, P. Kim, H.J. Kim, S.S. Kim, N.W. Sohn, et al., Ginsenoside Rg3 improves recovery from spinal cord injury in rats via suppression of neuronal apoptosis, pro-inflammatory mediators, and microglial activation. Molecules 22(1), E122 (2017)CrossRefGoogle Scholar
  12. L.F. Li, X.Y. Zheng, D.P. Fan, S.Y. Yu, D. Wu, C.Y. Fan, et al., Release of celecoxib from a bi-layer biomimetic tendon sheath to prevent tissue adhesion. Mater. Sci. Eng. C Mater. Biol. Appl. 61, 220–226 (2016)CrossRefGoogle Scholar
  13. J.N. Li, X.R. Feng, B.C. Liu, Y.J. Yu, L.M. Sun, T.J. Liu, et al., Polymer materials for prevention of postoperative adhesion. Acta Biomater. 61, 21–40 (2017)CrossRefGoogle Scholar
  14. J. Li, W. Xu, J. Chen, D. Li, K. Zhang, T. Liu, et al., Highly bioadhesive polymer membrane continuously releases cytostatic and anti-inflammatory drugs for peritoneal adhesion prevention. ACS Biomater. Sci. Eng. 4(6), 2026–2036 (2018a)CrossRefGoogle Scholar
  15. J.N. Li, W.G. Xu, D. Li, T.J. Liu, Y.S. Zhang, J.X. Ding, et al., Locally deployable nanofiber patch for sequential drug delivery in treatment of primary and advanced Orthotopic hepatomas. ACS Nano 12(7), 6685–6699 (2018b)CrossRefGoogle Scholar
  16. S. Liu, C. Hu, F. Li, X.J. Li, W. Cui, C. Fan, Prevention of peritendinous adhesions with electrospun ibuprofen-loaded poly(L-lactic acid)-polyethylene glycol fibrous membranes. Tissue Eng. A 19(3–4), 529–537 (2013)CrossRefGoogle Scholar
  17. H.-Y. Lo, H.-T. Kuo, Y.-Y. Huang, Application of Polycaprolactone as an anti-adhesion biomaterial film. Artif. Organs 34(8), 648–653 (2010)Google Scholar
  18. Y.S. Lui, M.P. Lewis, S.C. Loo, Sustained-release of naproxen sodium from electrospun-aligned PLLA-PCL scaffolds. J. Tissue Eng. Regen. Med. 11, 1011–1021 (2015)CrossRefGoogle Scholar
  19. H.M. Luo, D.F. Zhu, Y. Wang, Y.H. Chen, R.Z. Jiang, P. Yu, et al., Study on the structure of ginseng Glycopeptides with anti-inflammatory and analgesic activity. Molecules 23(6) (2018)CrossRefGoogle Scholar
  20. H.-M.D. Luu, A. Chen, I.S. Isayeva, Comparative stability of the bioresorbable ferric crosslinked hyaluronic acid adhesion prevention solutions. J Biomed Mater Res B Appl Biomater 101B(6), 1006–1013 (2013)CrossRefGoogle Scholar
  21. M.B. Malec-Milewska, W. Tarnowski, A.E. Ciesielski, E. Michalik, M.R. Guc, J.A. Jastrzebski, Prospective evaluation of pain control and quality of life in patients with chronic pancreatitis following bilateral thoracoscopic splanchnicectomy. Surg. Endosc. 27(10), 3639–3645 (2013)CrossRefGoogle Scholar
  22. B. Martina, K. Kateřina, R. Miloslava, G. Jan, M. Ruta, Oxycellulose: Significant characteristics in relation to its pharmaceutical and medical applications. Adv. Polym. Technol. 28(3), 199–208 (2009)CrossRefGoogle Scholar
  23. K. Olmarker, Reduction of adhesion formation and promotion of wound healing after laminectomy by pharmacological inhibition of pro-inflammatory cytokines: An experimental study in the rat. Eur. Spine J. 19(12), 2117–2121 (2010)CrossRefGoogle Scholar
  24. J.Y. Park, P. Choi, T. Kim, H. Ko, H.K. Kim, K.S. Kang, et al., Protective effects of processed ginseng and its active Ginsenosides on cisplatin-induced nephrotoxicity: In vitro and in vivo studies. J. Agric. Food Chem. 63(25), 5964–5969 (2015)CrossRefGoogle Scholar
  25. L.A. Sena, N.S. Chandel, Physiological roles of mitochondrial reactive oxygen species. Mol. Cell 48(2), 158–167 (2012)CrossRefGoogle Scholar
  26. R.K. Singh, E. Lui, D. Wright, A. Taylor, M. Bakovic, Alcohol extract of north American ginseng (Panax quinquefolius) reduces fatty liver, dyslipidemia, and other complications of metabolic syndrome in a mouse model. Can. J. Physiol. Pharmacol. 95(9), 1046–1057 (2017)CrossRefGoogle Scholar
  27. Y.F. Sun, S.Q. Chen, R.M. Wei, X. Xie, C.C. Wang, S.H. Fan, et al., Metabolome and gut microbiota variation with long-term intake of Panax ginseng extracts on rats. Food Funct. 9(6), 3547–3556 (2018)CrossRefGoogle Scholar
  28. H. Tokgöz, S. Bektaş, V. Hancı, B. Erol, B. Akduman, K. Karakaya, et al., Postoperative adhesions after application of topical hemostatic agents: Outcomes in a rat partial nephrectomy model. Urology 78(4), 970.e9–970.e14 (2011)CrossRefGoogle Scholar
  29. Y. Tokita, M. Yamamoto, K. Satoh, M. Nishiyama, S. Iizuka, S. Imamura, et al., Possible involvement of the transient receptor potential Vanilloid type 1 channel in postoperative adhesive obstruction and its prevention by a Kampo (traditional Japanese) medicine, Daikenchuto. J. Pharmacol. Sci. 115(1), 75–83 (2011)CrossRefGoogle Scholar
  30. Z. Zhang, J. Ni, L. Chen, L. Yu, J. Xu, J. Ding, Biodegradable and thermoreversible PCLA–PEG–PCLA hydrogel as a barrier for prevention of post-operative adhesion. Biomaterials 32(21), 4725–4736 (2011)CrossRefGoogle Scholar
  31. X. Zhao, S. Jiang, S. Liu, S. Chen, Z.Y. Lin, G. Pan, et al., Optimization of intrinsic and extrinsic tendon healing through controllable water-soluble mitomycin-C release from electrospun fibers by mediating adhesion-related gene expression. Biomaterials 61, 61–74 (2015)CrossRefGoogle Scholar
  32. Z. Zheng, W. Zhang, W. Sun, X. Li, J. Duan, J. Cui, et al., Influence of the carboxymethyl chitosan anti-adhesion solution on the TGF-β1 in a postoperative peritoneal adhesion rat. J. Mater. Sci. Mater. Med. 24(11), 2549–2559 (2013)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.China-Japan Union Hospital of Jilin UniversityChangchunChina
  2. 2.Department of PathologyThe Second Hospital of Jilin UniversityChangchunChina
  3. 3.The First Hospital of Jilin UniversityChangchunChina

Personalised recommendations