Low density lipoprotein - rosiglitazone - chitosan-calcium alginate/nanoparticles inhibition of human tenon's fibroblasts activation and proliferation

Abstract

Anti-fibrotic therapeutic methods with safety and efficiency after glaucoma filtration surgery (GFS) are desirable. In our previous study, by using Human Tenon's Fibroblasts (HTFs) as a model, we proved the expression of peroxisome proliferator activates receptor-γ (PPAR-γ) in HTFs; in addition, rosiglitazone (RSG), an agonist of PPAR-γ, can inhibit transforming growth factorsβ1 (TGF-β1)-induced reactivation of HTFs, thus to inhibit specifically scarring after GFS through intervening TGF-β/Smads signal pathway. However, a better drug delivery way of RSG, to prolong the duration of its function, and to reduce the toxicity of RSG to ocular tissue still remains challenges. Low density lipoprotein receptor (LDLr) is strongly expressed in hyper-proliferation HTFs after GFS. Therefore, we structured targeting LDL-RSG complexes and channel them into HTFs through LDL-LDLr pathway in order to promote anti-proliferation of HTFs and reduce the toxicity to ocular tissue. Meanwhile, in order to improve the release properties of LDL-RSG complexes, we structured slow release system of LDL-RSG/chitosan-calcium alginate - nanoparticles (CSNP), which effectively inhibited TGF-β1-induced HTFs proliferation, synthesis of extracellular matrix and activation of TGF-β1/SMAD pathway. These data suggested that LDL-RSG/CSNP can be a new anti-fibrotic therapeutic method on scarring after GFS and also a novelty administration of RSG.

Chitosan and its Derivatives for Ocular Delivery Formulations: Recent Advances and Developments

“…The optimized formulation, based on ALG, showed a better antimicrobial activity than lomefloxacin solution, which was attributed either to the presence of CS and/or to the overall higher efficiency of the formulation. Gong et al investigated CS/calcium alginate NPs as nanocarrier systems for the delivery of low-density lipoprotein-rosiglitazone complexes, aiming at a prolonged released and a reduction of toxic adverse side effects [171]. Specifically, the lipoprotein-rosiglitazone complex was synthesized via an incubation exchange method and then added to CS/calcium alginate NPs.…”

The Smad2/3/4 complex binds miR‐139 promoter to modulate TGFβ‐induced proliferation and activation of human Tenon's capsule fibroblasts through the Wnt pathway

“…We obtained Tenon's biopsy specimens from our previous study (Gong, Yin, Tong, Zeng, & Xiong, 2017) with the approval of the Medicine Human Ethics Committee of the Second Xiangya Hospital of the Central South University. HTFs were gained and cultured complied with the previous methods (Gong et al, 2017).…”

“…We obtained Tenon's biopsy specimens from our previous study (Gong, Yin, Tong, Zeng, & Xiong, 2017) with the approval of the Medicine Human Ethics Committee of the Second Xiangya Hospital of the Central South University. HTFs were gained and cultured complied with the previous methods (Gong et al, 2017). Tenon's biopsy samples were obtained during standard glaucoma-filtering surgery after comprehensive information and written consent of selected patients.…”

Rosiglitazone inhibits PM2.5-induced cytotoxicity in human lung epithelial A549 cells

“…Rosiglitazone, one of the agonists of PPARγ, is a thiazolidinedione drug used in the treatment of type 2 diabetes mellitus (13). In recent years, the resistance function of rosiglitazone in cell apoptosis, inflammation response and oxidative stress have been verified (14)(15)(16)(17). However, whether rosiglitazone is able to prevent cell injury and death in lung epithelial cells resulted from PM2.5 still remains unclear.…”