Self-assembled polymeric micelles for combined delivery of anti-inflammatory gene and hydrophobic drug for acute lung injury therapy

Title
Self-assembled polymeric micelles for combined delivery of anti-inflammatory gene and hydrophobic drug for acute lung injury therapy
Other Titles
급성폐손상 치료제로써 고분자 마이쉘을 이용한 항염증 유전자와 소수성 약물의 복합전달
Author
Gyeung Yun, Kim
Alternative Author(s)
김경윤
Advisor(s)
이민형
Issue Date
2019-02
Publisher
한양대학교
Degree
Master
Abstract
Acute lung injury (ALI) is a lung inflammatory disease for which pulmonary delivery of drug and genecould be a useful strategy. In this study, cholesterol-conjugated polyamidoamine (PAM-Chol) was synthesized and characterized as a carrier for combined delivery of anti-inflammatory gene and drug into the lungs by inhalation. The PAM-Chol formed self-assembled micelles in an aqueous solution with a critical micelle concentration of 0.22 mg ml−1. An in vitro transfection assay to L2 lung epithelial cells showed that the PAM-Chol micelle had higher transfection efficiency than lipofectamine and polyethylenimine (25 kDa, PEI25k). As the anti-inflammatory drug, resveratrol was loaded into the cores of the PAM-Chol micelles using the oil-in-water emulsion/solvent evaporation method. In lipopolysaccharide (LPS)-activated macrophage cells, resveratrol-loaded PAM-Chol (PAM-Chol/Res) and curcumin-loaded PAM-Chol (PAM-Chol/Cur) reduced pro-inflammatory cytokines, confirming the possibility of delivering hydrophobic drug by PAM-Chol. In in vitro transfection assays to L2 cells, the PAM-Chol/Res or PAM-Chol/Cur micelles had similar transfection efficiency to that of PAM-Chol. The delivery of resveratrol or curcumin with the heme oxygenase-1 gene (pHO-1) by inhalation was evaluated in an ALI animal model. Resveratrol and curcumin delivery using the PAM-Chol micelles inhibited the nuclear translocation of nuclear factor-κB (NF-κB) and reduced pro-inflammatory cytokines in the lungs. pHO-1 delivery using PAM-Chol induced HO-1 expression and reduced pro-inflammatory cytokines. However, the highest anti-inflammatory effects were obtained with combined delivery of pHO-1 and drug using the pHO-1/PAM-Chol/drug complex, as demonstrated in cytokine assays and immunohistochemical studies. Therefore, the PAM-Chol micelle is an efficient carrier of hydrophobic drug and pHO-1 into the lungs and could be useful for the treatment of ALI by inhalation.
URI
http://dcollection.hanyang.ac.kr/common/orgView/000000108364http://repository.hanyang.ac.kr/handle/20.500.11754/99329
Appears in Collections:
GRADUATE SCHOOL[S](대학원) > BIOENGINEERING(생명공학과) > Theses (Master)
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