Absorbable 3D-printed pancreaticojejunostomy device with a dual-layer drug coating for the prevention of postoperative local recurrence of pancreatic cancer

doi:10.1016/j.jmst.2023.01.016

Abstract

Abstract: The high local recurrence rate of pancreatic cancer after surgery is one of the important risk factors affecting patient survival. The traditionally used silicone tube stent is not only complicated to operate but also lacks antitumor properties. The purpose of this study was to develop a dual-layer drug-coated pancreaticojejunostomy device. The coating consisted of two layers, an outer basic fibroblast growth factor (bFGF) coating layer and an inner nanoparticle albumin-bound paclitaxel (nab-PTX) coating layer with chitosan as the drug-carrying medium. Due to the diffusion barrier from the outer coating, the release of nab-PTX from the inner layer was delayed and slowed down. We studied the degradation rates, mechanical properties, surface morphologies, drug release kinetics, promoting the growth of fibroblasts and antitumor properties of the coated stents. It was found that 100 ng of bFGF and 50 µg of nab-PTX were suitable drug concentrations that can effectively promote the growth of fibroblasts and inhibit pancreatic cancer cells. The results also confirmed that the dual-layer drug-coated pancreaticojejunostomy device showed good antitumor activity both in vitro and in vivo without obvious systemic toxicity. In addition, the device has a suitable degradation rate. In conclusion, this biodegradable dual-layer drug-coated pancreaticojejunostomy device can potentially inhibit the local recurrence of pancreatic cancer after surgery and promote the healing of pancreaticointestinal anastomosis. This device has great potential to treat pancreatic cancer in the future.

Key words: Pancreaticojejunostomy device, 3D printing, Drug coating, Anti-tumor effect, Pancreatic cancer

Maoen Pan, Tingting Huang, Zeya Xu, Wei Luo, Yuanyuan Yang, Tianhong Teng, Heguang Huang. Absorbable 3D-printed pancreaticojejunostomy device with a dual-layer drug coating for the prevention of postoperative local recurrence of pancreatic cancer[J]. J. Mater. Sci. Technol., 2023, 154: 178-188.

References

[1] V.P. Groot, N. Rezaee, W. Wu, J.L. Cameron, E.K. Fishman, R.H. Hruban, M.J. Weiss, L. Zheng, C.L. Wolfgang, J. He, Ann. Surg. 267(2018) 936-945.
[2] R.P. Jones, E.E. Psarelli, R. Jackson, P. Ghaneh, C.M. Halloran, D.H. Palmer, F. Campbell, J.W. Valle, O. Faluyi, D.A.O’Reilly, D.Cunningham, J. Wadsley, S. Darby, T. Meyer, R. Gillmore, A. Anthoney, P. Lind, B. Glimelius, S. Falk, J.R. Izbicki, G.W. Middleton, S. Cummins, P.J. Ross, H. Wasan, A. McDonald, T. Crosby, Y. Ting, K. Patel, D. Sherriff, R. Soomal, D. Borg, S. Sothi, P. Ham-mel, M.M. Lerch, J. Mayerle, C. Tjaden, O. Strobel, T. Hackert, M.W. Buchler, J.P. Neoptolemos, C. European Study Group for Pancreatic, JAMA Surg. 154(2019) 1038-1048.
[3] C. Tjaden, C.W. Michalski, O. Strobel, N. Giese, A.K. Hennche, M.W. Buchler, T. Hackert, Pancreas 45 (2016) 895-899.
[4] J.B. Wolinsky, Y.L. Colson, M.W. Grinstaff, J. Control Release 159 (2012) 14-26.
[5] T. Manabe, H. Okino, R. Maeyama, K. Mizumoto, E. Nagai, M. Tanaka, T. Mat-suda, J. Control Release 100 (2004) 317-330.
[6] M. Westphal, D.C. Hilt, E. Bortey, P. Delavault, R. Olivares, P.C. Warnke, I.R. Whittle, J. Jaaskelainen, Z. Ram, Neuro. Oncol. 5(2003) 79-88.
[7] L. Indolfi, M. Ligorio, D.T. Ting, K. Xega, A.R. Tzafriri, F. Bersani, N. Aceto, V. Tha-par, B.C. Fuchs, V. Deshpande, A.B. Baker, C.R. Ferrone, D.A. Haber, R. Langer, J.W. Clark, E.R. Edelman, Biomaterials 93 (2016) 71-82.
[8] S.K. Nandi, S. Bandyopadhyay, P. Das, I. Samanta, P. Mukherjee, S. Roy, B. Kundu, Biotechnol. Adv. 34(2016) 1305-1317.
[9] C.G. Zalavras, M.J. Patzakis, P. Holtom, Clin. Orthop. Relat. Res. 427(2004) 86-93.
[10] A.D. Hanssen, Clin. Orthop. Relat. Res. 437(2005) 91-96.
[11] S. Attanasio, J. Snell, Cardiol. Rev. 17(2009) 115-120.
[12] C.J. Kearney, D.J. Mooney, Nat. Mater. 12(2013) 1004-1017.
[13] J. Xue, N. Sun, Y. Liu, Int. J. Nanomed. 17(2022) 2459-2474.
[14] N. Mayet, Y.E. Choonara, P. Kumar, L.K. Tomar, C. Tyagi, L.C.Du Toit, V.Pillay, J. Pharm. Sci. 103(2014) 2211-2230.
[15] H. Brem, S. Piantadosi, P.C. Burger, M. Walker, R. Selker, N.A. Vick, K. Black, M. Sisti, S. Brem, G. Mohr, P. Muller, R. Morawetz, S.C. Scholdet, The Poly-mer-brain Tumor Treatment Group. Lancet 345 (1995) 1008-1012.
[16] A. Fakhari, J. Anand Subramony, J. Control Release 220 (2015) 465-475.
[17] S. Son, S. Song, S.J. Lee, S. Min, S.A. Kim, J.Y. Yhee, M.S. Huh, I. Chan Kwon, S.Y. Jeong, Y. Byun, S.H. Kim, K. Kim, Biomaterials 34 (2013) 9475-9485.
[18] C. Li, Y. Li, Y. Gao, N. Wei, X. Zhao, C. Wang, Y. Li, X. Xiu, J. Cui, Int. J. Pharm. 468(2014) 15-25.
[19] F. Nowruzi, R. Imani, S. Faghihi, Sci. Rep. 12(2022) 8595.
[20] M. Arafat, Y. Song, K. Brewer, P. Fouladian, A. Parikh, H. Albrecht, A. Blencowe, S. Garg, Drug Des. Devel. Ther. 15(2021) 1495-1507.
[21] A. Anitha, S. Sowmya, K. Sudheesh, S. Deepthi, K.P. Chennazhia, H. Ehrlich, M. Tsurkan, R. Jayakumar, Prog. Polym. Sci. 39(2014) 1644-1667.
[22] M. Pan, C. Zhao, Z. Xu, Y. Yang, T. Teng, J. Lin, H. Huang, * *, * *, * *, Front Bioeng. Biotechnol. 9 (2021) 686207 (n.d.).
[23] Y.Y. Yang, C.Q. Zhao, L.S. Wang, J.X. Lin, S.Z. Zhu, H.G. Huang, Mater. Sci. Eng. C Mater. Biol. Appl. 103 (2019) 109786 (n.d.).
[24] M.E. Pan, Z.Y. Xu, W. Luo, Y.Y. Yang, T.H. Teng, J.X. Lin, H.G. Huang, Mater. Des. 210(2021) 110088.
[25] W.P. Charteris, P.M. Kelly, L. Morelli, J.K. Collins, J. Appl. Microbiol. 84(1998) 759-768.
[26] M. Del Piano, P. Strozzi, M. Barba, S. Allesina, F. Deidda, P. Lorenzini, L. Morelli, S. Carmagnola, M. Pagliarulo, M. Balzarini, M. Ballare, M. Orsello, F. Montino, M. Sartori, E. Garello, L. Capurso, L. Gastroenterol. 42 (Suppl 3 Pt 2) (2008) S170-S173.
[27] T. Teng, R. Lin, Z. Lin, K. Ke, X. Lin, M. Pan, D. Zhang, H. Huang, Biomater. Sci. 8(2020) 3278-3285.
[28] M.S. Singhvi, S.S. Zinjarde, D.V. Gokhale, J. Appl. Microbiol. 127(2019) 1612-1626.
[29] C.M. Han, E. Lih, S.K. Choi, T.M. Bedair, Y.J. Lee, W. Park, D.K. Han, J.S. Son, Y.K. Joung, J. Ind. Eng.Chem. 67(2018) 396-406.
[30] F. Zhao, W. Xue, F. Wang, J. Sun, J. Lin, L. Liu, K. Sun, L. Wang, J. Mech. Behav.Biomed. Mater. 89(2019) 19-32.
[31] A. Martineza, I. Iglesias, R. Lozano, J.M. Teijon, M.D. Blanco, Carbohydr. Polym. 83(2011) 1311-1321.
[32] J. Wang, G. Wang, H. Shan, X. Wang, C. Wang, X. Zhuang, J. Ding, X. Chen, Biomater. Sci. 7(2019) 963-974.
[33] L.C. Su, Y.H. Chen, M.C. Chen, ACS Appl. Mater. Interfaces 5 (2013) 12944-12953.
[34] G. Li, Y. Chen, J. Hu, X. Wu, J. Hu, X. He, J. Li, Z. Zhao, Z. Chen, Y. Li, H. Hu, Y. Li, P. Lan, Biomaterials 34 (2013) 9451-9461.
[35] L. Li, D. Chen, K. Zheng, L. Jiang, T. Dai, L. Yang, L. Jiang, Z. Chen, C. Yuan, M. Huang, ACS Appl. Mater. Interfaces 12 (2020) 4221- 4230.
[36] Z. Farrukh, M. Thiagarajan, P. Jithendra, R. Taliyan, P. Kesharwani, J. Pharm. Sci. 110(2021) 3111-3117.
[37] N. Kumari, V. Mathe, C. Krishna, P. Dongre, J. Biomol. Struct.Dyn. 40(2022) 9253-9269.
[38] R. Kinoshita, Y. Ishima, V. Chuang, H. Nakamura, J. Fang, H. Watanabe, T. Shimizu, K. Okuhira, T. Ishida, H. Maeda, M. Otagiri, T. Maruyama, Bioma-terials 140 (2017) 162-169.