Lecithin-based nanocapsule loading sucupira (Pterodon emarginatus) oil effects in experimental mucositis

Abstract

Intestinal mucositis (IM) is a frequent adverse effect in anticancer therapy without standard treatment. The oil obtained from sucupira (Pterodon emarginatus) has anti-inflammatory properties, and the soybean lecithin reduces the intestinal toxicity of several xenobiotics. However, their water insolubility impairs the in vivo application. For this reason, we evaluated if the nanoencapsulation of sucupira oil (SO) in lecithin-based nanocapsules (SO-NC) could be a therapeutically effective system for the treatment of IM in murine cisplatin (CDDP)-induced intestinal mucositis model. SO was analyzed by LC-HRMS/MS and HPLC. SO-NC was prepared by nanoprecipitation and characterized using DLS, HPLC, and AFM. Mice body weight and food consumption were assessed daily during experimental mucositis induced by CDDP. The animals were euthanized, and intestinal permeability, inflammatory mediators, and intestinal histology were performed. SO-NC demonstrated adequate characteristics for oral administration as size under 300 nm, IP < 0.3, high EE, and spherical shape. In vitro cytotoxicity performed against RAW 264.7 cell lines resulted in cell viability above 80 % confirming the non-cytotoxic profile of SO (IC₅₀ 268 µg/mL) and SO-NC (IC₅₀ 118.5 µg/mL) up to 117.2 µg/mL. The untreated mice showed intestinal toxicity after i.p. of CDDP, principally weight loss, increased intestinal permeability, and MPO and TNF-α levels. Surprisingly, the administration of SO to CDDP-mucositis animals did not circumvent the CDDP effects and increased intestinal permeability. However, SO-NC proved efficient in mitigating the experimental intestinal mucositis by improving intestinal epithelium architecture, reducing intestinal permeability, and improving the MPO levels. In conclusion, SO-NC can positively impact intestinal mucositis by promoting mucosal recovery. This is a promising strategy for developing a new treatment for intestinal mucositis.

Keywords: Intestinal permeability; Lecithin; Mucositis; Nanocapsules; Pterodon emarginatus.

Graphical abstract

Fig. 1

- LC-HRMS/MS analysis in negative electrospray ionization mode for the P. emarginatus oil-resin. A) LC-HRMS base peak chromatogram. B) MS² Spectra of peaks 1, 3–9. (Peak 2 was not fragmented due to low concentration).

Fig. 2

- Atomic force microscopy images of SO-NC (scale 5 × 5 µm).

Fig. 3

- Physical stability of SO-NC during storage at 25 °C and 4 °C for four weeks.*versus control; P < 0.05.

Fig. 4

- Cytotoxicity assay performed in RAW 264.7 macrophage cell line. * P < 0.05. Abbreviations: SO, sucupira oil; SO-NC, lecithin based-nanocapsules containing sucupira oil.

Fig. 5

- Body weight changes and food consumption across groups in ( %) healthy (A, C) and CDDP-induced intestinal mucositis (B, D) in Swiss mice. Data are expressed as mean ± SEM of 6 animals per group. *versus day 0; P < 0.05. Abbreviations: CDDP: mucositis group; SO, sucupira oil; SO-NC, lecithin based-nanocapsules containing sucupira oil.

Fig. 6

- Evaluation of intestinal permeability by ^99 mTc-DTPA. Data are presented as mean ± SEM of 6 animals per group. Different letters indicate statistically significant differences (P < 0.05). Abbreviations: CDDP: mucositis group; SO, sucupira oil; SO-NC, lecithin based-nanocapsules containing sucupira oil; ID/g, injected dose per gram.

Fig. 7

- Histopathological ileum analysis. Photos are representative images, 20x magnification. Data are expressed as media ± SEM of 6 animals per group.

Fig. 8

- Activity of myeloperoxidase (MPO) (A), N-acetylglucosaminidase (NAG) (B), Levels of TNF-α (C), and IL-10 (D) cytokines of the ileum. Data are expressed as media ± SEM of 6 animals per group. Different letters indicate statistically significant differences (P < 0.05). Abbreviations: CDDP: mucositis group; SO, sucupira oil; SO-NC, lecithin based-nanocapsules containing sucupira oil.