İDİYOPATİK PULMONER FİBROZİS (İPF) TEDAVİSİNDE KULLANILMAK ÜZERE NİNTEDANİB VE miR-29b YÜKLÜ LİPOPLEKS FORMÜLASYONLARININ GELİŞTİRİLMESİ, KARAKTERİZE EDİLMESİ VE TEDAVİ ETKİNLİKLERİNİN İPF HÜCRE KÜLTÜRÜ MODELİNDE DEĞERLENDİRİLMESİ

Abstract

Idiopathic pulmonary fibrosis (IPF) is a disease with a high mortality rate, caused by cellular stress and tissue damage in the lungs, leading to the excessive accumulation of extracellular matrix (ECM) components that disrupts lung structure and function. Current treatment options are limited due to their side effects, highlighting the need for alternative therapies. This study aims to develop a cationic lipoplex formulation loaded with Nintedanib and miR-29b (LP-NIN-miR) for the treatment of IPF and to investigate its anti-fibrotic effects in an in vitro lung fibrosis model. In this study, cationic liposomes were optimized using a Quality by Design (QbD) approach. The optimized liposome formulation was prepared using DOTAP, CHOL, DOPE, and DSPE-mPEG 2000. Nintedanib-loaded liposomes (LP-NIN) were produced using a microfluidization method and incubated with miR-29b to obtain LP-NIN-miR. The particle size, polydispersity index, and zeta potential of LP-NIN-miR were determined to be 87.3 ± 0.9 nm, 0.184 ± 0.003, and +24 ± 1 mV, respectively. The encapsulation efficiencies of Nintedanib and miR-29b were found to be over 99%. Cytotoxicity studies demonstrated that LP-NIN-miR is a safe delivery system, and transfection studies confirmed its anti-fibrotic therapeutic effect. This study marks an important step toward the development of an innovative therapeutic approach for IPF treatment.