Abstract: FR-OR010
Nanoparticles of Lipids with Paclitaxel Reverse Inflammation and Peritoneal Fibrosis in the Peritoneal Fibrosis Model in Uremic Rats
Session Information
- Advances in Home Dialysis Modalities
October 26, 2018 | Location: 2, San Diego Convention Center
Abstract Time: 06:18 PM - 06:30 PM
Category: Dialysis
- 703 Dialysis: Peritoneal Dialysis
Authors
- Costalonga, Elerson, School of Medicine, University of Sao Paulo, São Paulo, SÃO PAULO, Brazil
- Pepineli, Rafael, University of Sao Paulo, Sao Paulo, Brazil
- Maranhão, Raul Cavalcante, Instituto do Coração do HCFMUSP, Sao Paulo, Brazil
- Noronha, Irene L., University of Sao Paulo, Sao Paulo, Brazil
Background
Increased cellular proliferation and inflammation of the peritoneal membrane (PM) are complications of long term peritoneal dialysis leading to peritoneal fibrosis (PF). Paclitaxel, a potent antiproliferative drug, has therapeutic efficacy, limited by toxicity. Nanotechnology enabled drug release systems that can concentrate the active drug on target tissues. LDE, a LDL similar nanoparticle, was associated to Paclitaxel (NanoPACLI) in order to reduce drug toxicity. NanoPACLI binds to LDL receptors, which are overexpressed on the cell surface of inflamed tissues. In this study, the effects of NanoPACLI administration in a model of experimental PF associated to uremia were analyzed.
Methods
Uremia was induced in male Wistar rats fed with adenine-containing diet during a period of 21 days. Injections of chlorhexedine gluconate (CG) were administrated intraperitoneally (IP) to induce PF. Rats (n=27) were divided into 3 groups: Control, normal rats receiving saline injections; PF/CKD, uremic rats receiving CG injections; PF/CKD-NanoPACLI, uremic rats with PF receiving NanoPACLI injections (IP; 4mg/kg every 3 days). The NanoPACLI treatment was initiated 7 days after PF induction. Euthanasia was performed on day 21. PM thickness, ultrafiltration (UF), inflammatory cell infiltration, and cytokine expression were analyzed.
Results
NanoPACLI significantly decreased peritoneal thickness, prevented UF failure, reduced inflammatory cellular infiltration as well as cytokine concentration in the PM.
Conclusion
NanoPACLI administration was effective in inhibiting the progression of PF and preserving UF in a model of established PF in uremic rats. These findings may be related to the anti-inflammatory effects of paclitaxel delivered locally by NanoPACLI.
Effects of NanoPACLI on PF model in uremic rats
| Control | PF/CKD | PF/CKD-NanoPACLI | |
| BUN (mg/dL) | 21±2 | 97±12** | 91±6** |
| Peritoneal Thickness (μm) | 17.2±2.2 | 91.4±16.3*** | 45.9±7.8 |
| UF (ml) | 15.9±3.3 | -2.2±1.3*** | 3.3±1.4 |
| Macrophages (cells/mm2) | 72.4±18.8 | 347±137* | 97.1±32.9 |
| T-cells (cells/mm2) | 11.6±9.2 | 299.4±64.9** | 100.2±74.8 |
| IL-1β (pg/ml) | 39.9±5.4 | 377.3±115.3* | 129.4±21.5 |
| TNF-α (pg/ml) | 1.7±0.2 | 50.8±24.3* | 4.9±2.6 |
| INF-γ (pg/ml) | 9.3±3.06 | 45.3±12.1** | 7.4±2.4 |
Results were expressed as mean±SEM. *p<0.05;**p<0.01,***p<0.001