The Clinical Implication of Vitamin D Nanomedicine for Peritoneal Dialysis-Related Peritoneal Damage

Yi-Che Lee,1–3 Chih-Ting Huang,4 Fong-Yu Cheng,5 Shih-Yuan Hung,3,6 Tsun-Mei Lin,7 Yen-Chang Tsai,4 Chih-I Chen,8 Hao-Kuang Wang,9 Chi-Wei Lin,10 Hung-Hsiang Liou,11 Min-Yu Chang,3 Hsi-Hao Wang,3 Yuan-Yow Chiou4,12 1Division of Nephrology, Department of Internal Medicine, E-DA Dachang Hospital/ I-Shou University, Kaohsiung, Taiwan; 2School of Medicine, College of Medicine; 3Division of Nephrology, Department of Internal Medicine, E-DA Hospital/ I-Shou University, Kaohsiung, Taiwan; 4Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 5Department of Chemistry, Chinese Culture University, Taipei, Taiwan; 6School of Medicine for International Students; 7Department of Laboratory Medicine; 8Division of Colorectal Surgery, Department of Surgery; 9Department of Neurosurgery; 10Department of Medical Education, E-DA Hospital/ I-Shou University, Kaohsiung, Taiwan; 11Division of Nephrology, Department of Medicine, Hsin-Jen Hospital, New Taipei City, Taiwan; 12Department of Pediatrics, National Cheng Kung University Hospital, Tainan, TaiwanCorrespondence: Yi-Che LeeDivision of Nephrology, Department of Internal Medicine, E-DA Hospital/I-Shou University, No.1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung City 82445, Taiwan, ROCTel +886-7-6150011 ext. 5121Email pipijer@gmail.com Yuan-Yow ChiouInstitute of Clinical Medicine, Department of Pediatrics, National Cheng Kung University Hospital, Medical College, No. 138, Sheng-Li Road, Tainan City 701, Taiwan, ROCTel +886-6-2353535 ext. 4184Fax +886-6-2753083Email yuanyow@mail.ncku.edu.twPurpose: Vitamin D is a novel potential therapeutic agent for peritoneal dialysis (PD)-related peritoneal fibrosis, but it can induce hypercalcemia and vascular calcification, which limits its applicability. In this study, we create nanotechnology-based drug delivery systems to investigate its therapeutics and side effects.Materials and methods: 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N- [amino-(polyethylene glycol)2000] (DSPE-PEG) and L-α-phosphatidylcholine (PC), which packages with 1α,25(OH)2D3, were used to construct vitamin D nanoliposomes. To confirm the function and safety of vitamin D nanoliposomes, peritoneal mesothelial cells were treated with TGF-β1 and the reverse was attempted using vitamin D nanoliposomes. Antibodies (Ab) against the peritoneum-glycoprotein M6A (GPM6A) Ab were conjugated with vitamin D nanoliposomes. These particles were implanted into mice by intraperitoneal injection and the animals were monitored for the distribution and side effects induced by vitamin D.Results: Vitamin D nanoliposomes were taken up by the mesothelial cells over time without cell toxicity and it also provided the same therapeutic effect in vitro. In vivo study, fluorescent imaging showed vitamin D nanoliposomes allow specific peritoneum target effect and also ameliorate vitamin D side effect.Conclusion: Nanoliposomes vitamin D delivery systems for the prevention of PD-related peritoneal damage may be a potential clinical strategy in the future.Keywords: peritoneal dialysis, nanoliposome, vitamin D, fibrosis