Use of paclitaxel carried in lipid nanoparticles to treat aortic allograft transplantation in rats

Author(s)

Pepineli, Rafael ^[1] ; Santana, Alexandre C. ^[1] ; Silva, Filipe M. O. ^[1] ; Tavoni, Thauany M. ^[2] ; Stolf, Noedir A. G. ^[2] ; Noronha, Irene L. ^[1] ; Maranhao, Raul C. ^{[3, 2]}

Affiliation

^[1] Univ Sao Paulo, Fac Med, Div Nefrol, Lab Nefrol Celular & Mol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Med, Hosp Clin HCFMUSP, Inst Coracao InCor, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Fac Ciencias Farmaceut, Sao Paulo - Brazil

• Document type: Journal article
• Source: Journal of Pharmacy and Pharmacology; v. 73, n. 8, p. 1092-1100, AUG 2021.
• Web of Science Citations: 0

Abstract

Objectives The aim of this study was to test whether lipid core nanoparticles loaded with paclitaxel (LDE-PTX) protect rat aortic allograft from immunological damage. Methods Fisher and Lewis rats were used differing in minor histocompatibility loci. Sixteen Lewis rats were allocated to four-animal groups: SYNG (syngeneic), Lewis rats receiving aorta grafts from Lewis rats; ALLO (allogeneic), Lewis rats receiving aortas from Fisher rats; ALLO+LDE (allogeneic transplant treated with LDE), Lewis rats receiving aortas from Fisher rats, treated with LDE (weekly injection for 3 weeks); ALLO+LDE-PTX (allogeneic transplant treated with LDE-PTX), Lewis rats receiving aortas from Fisher rats treated with LDE-PTX (4 mg/kg weekly for 3 weeks). Treatments began on transplantation day. Results Thirty days post-transplantation, SYNG showed intact aortas. ALLO and ALLO+LDE presented intense neointimal formation. In ALLO+LDE-PTX, treatment inhibited neointimal formation; narrowing of aortic lumen was prevented in ALLO and ALLO+LDE. LDE-PTX strongly inhibited proliferation and intimal invasion by smooth muscle cells, diminished 4-fold presence of apoptotic/dead cells in the intima, reduced the invasion of aorta by macrophages and T-cells and gene expression of pro-inflammatory tumour necrosis factor-alpha (TNF alpha), interferon gamma (IFN gamma) and interleukin-1 beta (IL-1 beta). Conclusions LDE-PTX was effective in preventing the vasculopathy associated with rejection and may offer a potent therapeutic tool for post-transplantation. (AU)

• FAPESP's process: 14/03742-0 - Nanoparticles that bind to lipoprotein receptors in the treatment atherosclerosis, acute myocardial infarction, post-heart transplantation status, cancer and endometriosis
• Grantee: Raul Cavalcante Maranhao
• Support Opportunities: Research Projects - Thematic Grants