Potential Preventive Effect of Orally Administered Paclitaxel-SBA-۱۵ Nanoparticles on Aortic Intima–Media Remodeling in High-Fat Diet-Fed Wistar Rats: An In Vivo Study

Atherosclerotic vascular remodeling involves endothelial dysfunction, inflammation, vascular smooth muscle cell responses, and progressive intimal thickening. Paclitaxel exhibits antiproliferative activity, but its poor aqueous solubility, limited oral bioavailability, and systemic toxicity restrict its potential for prolonged systemic administration. This exploratory study evaluated whether orally administered paclitaxel-loaded SBA-۱۵ (PTX-SBA-۱۵) could attenuate aortic intima-to-media remodeling during high-fat diet (HFD) exposure in Wistar rats. Twenty-five male Wistar rats were randomly allocated to five groups (n = ۵ per group): a standard-diet control (K−), an untreated HFD control (K+), and three HFD groups receiving PTX-SBA-۱۵ at doses of ۵ mg/kg (P۱), ۷.۵ mg/kg (P۲), or ۱۰ mg/kg body weight (P۳). Treatment was initiated concurrently with the HFD and continued for eight weeks. Morphological characteristics of the formulation were examined using scanning electron microscopy (SEM). Aortic arch sections were stained with hematoxylin and eosin, and animal-level intima-to-media ratios were quantified using ImageJ. Differences among groups were analyzed using the Kruskal–Wallis test followed by Dunn’s test with Holm adjustment. Median intima-to-media ratios were ۰.۰۳۰۵ in K−, ۰.۱۳۶۵ in K+, ۰.۱۰۲۰ in P۱, ۰.۰۶۱۰ in P۲, and ۰.۰۵۹۰ in P۳. The overall group difference was significant (H = ۱۶.۵۳۴, P = ۰.۰۰۲). Significant pairwise differences were observed between K− and K+ (adjusted P = ۰.۰۰۱۹) and between K− and P۱ (adjusted P = ۰.۰۳۵۹). However, none of the PTX-SBA-۱۵ groups differed significantly from K+. These findings indicate numerically lower aortic intima-to-media ratios at the two higher doses but do not establish a statistically significant preventive effect compared with the untreated HFD group.

کلیدواژه ها:

Atherosclerosis ، Paclitaxel ، Aorta ، Mesoporous silica ، Intima-Media ratio