Vaginal inflammatory irritation of nifeviroc microemulsion thermosensitive gel in mini-pigs

TIAN Fang; WANG Yu-zhu; HUANG Chao; XIA Min-jie; ZHI Rui-na; SUN Bing; DING Xun-cheng; ZHOU Xin-chu; LI Wei-hua

Abstract：Objective:To evaluate the inflammatory irritation of nifeviroc microemulsion thermosensitive gel (NFVR/ME-TISG) in the vaginal mucosa of mini-pigs.Methods:Nine female pigs were randomly divided into matrix gel group,NFVR/ME-TISG group (25 mg·d-1) and nonoxynol-9 (N-9) jelly group (25 mg·d-1).Twelve days after estradiol benzoate intramuscular injection,5 mL of gel was administered intravaginally once daily to the mini-pigs for 7 days.Cervicovaginal lavages (CVLs) were collected predose and at 24,72 h after the final administration.The numbers of neutrophilic granulocytes were analyzed by flow cytometry.Vaginal tissue was collected at 72 h after the final administration.Vaginal sections from each specimen were assessed after hematoxylin & eosin (HE) staining,and scored for the following histological features:epithelial ulceration/erosion,necrosis,cell infiltration,hemorrhage,congestion and edema.The CD45+ expression in the vaginal mucosa was examined by the immunohistochemical (IHC) assay.Results:Compared to the matrix gel group,the number of neutrophilic granulocytes of the N-9 jelly group was significantly increased (P ＜ 0.01).The vaginal mucosa of the N-9 jelly group showed obvious histopathological changes including epithelium loss,inflammation,bleeding and edema.CD45+ expression in the vaginal mucosa in N-9 jelly group was increased significantly (P ＜ 0.05).However,NFVR/METISG group showed no obvious changes.Conslusion:NFVR/ME-TISG did not induce the inflammatory irritation in the vaginal mocusa of mini-pigs,so they are promising to be developed into a topical microbicide.