Development of a Short-Term Embolic Agent Based on Cilastatin for Articular Microvessels

Abstract

Background and Objectives: This study aimed to develop an embolic agent with short-term embolic effects using cilastatin as the basic material. Materials and Methods: The particle size distribution of 25 mg cilastatin-based short-term embolic agents was evaluated microscopically under three different mixing conditions. A total of thirty-six healthy male Sprague Dawley rats were divided into four groups. Each group of six rats was injected once into the tail artery with 0.4 mL each of (A) Cilastatin + D-Mannitol Mixture, (B) Iohexol, (C) Prepenem, and (D) embolization promoter (EGgel). Results: A visual inspection of the tail appearance of rats in each group was performed at 0, 3, 7, 15, and 21 days. At weeks 1 and 3, three rats per group were euthanized, and histopathological analyses were performed on the specimens obtained from each group. No significant differences were observed on day 7, but mild inflammation was observed in Group (D) on day 15. Histopathological inflammation scoring of tail central artery embolization was performed using a six-point scale (from 0 = absent to 5 = marked inflammation). Three groups were formed consisting of six male New Zealand white rabbits each: control, positive control, and test groups. The control group received an Iohexol injection (rabbits: 0.8 mL). The positive control and experimental groups were injected with prepenem and cilastatin/D-mannitol compound, respectively (0.8 mL), and vascular angiography was performed. The order of occlusion progression after embolization was as follows: test group, positive control group, and control group. Conclusions: We developed a cilastatin/D-mannitol compound that exhibits characteristics of short-term embolization by utilizing the pharmacokinetic properties of cilastatin and the crystalline material D-mannitol. We evaluated its particle size distribution microscopically, conducted histopathological evaluation including inflammation via animal experiments, and assessed the embolization effect.