건선에서 자가조립 히알루론산 나노입자의 기능 연구
functional characterization of a self-assembled hyaluronic acid nanoparticle as a nanomedicine for treatment of psoriasis
- 주제(키워드) 건선 , 히알루론산 , 나노파티클
- 발행기관 아주대학교
- 지도교수 김욱
- 발행년도 2019
- 학위수여년월 2019. 2
- 학위명 석사
- 학과 및 전공 일반대학원 분자과학기술학과
- 실제URI http://www.dcollection.net/handler/ajou/000000028610
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Since hyaluronic acid (HA) has good biocompatibility and nonimmunogenicity, self-assembled hyaluronic acid nanoparticles (HA-NPs) have been widely used for a drug carrier combined with active agents. Recently, it has been reported that empty HA-NPs not bearing any drugs have therapeutic effects on adipose tissue inflammation and insulin resistance. In this study, I investigated effects of HA-NPs itself on psoriasis; chronic and relapsing inflammatory skin disease. HA-NPs is an amphiphilic molecule that is composed with hydrophobic lithocholic acid (LCA) and hydrophilic HA, so it is self-assembled in particles which have hydrophilic surface and hydrophobic core in aqueous environment. In the imiquimod (IMQ)-induced mouse psoriasis model, topical treatment with HA-LCA nanoparticles (HA-LCA NPs) effectively reduced IMQ-induced epidermal proliferation, abnormal differentiation, and macrophage infiltration. Using monocyte cell line, I found that HA-LCA NPs inhibit monocyte differentiation into pro-inflammatory M1 macrophage and reduce expression levels of tumor necrosis factor-alpha (TNF-α), which is the central player of inflammation and psoriasis and induces inflammatory cascades and hyper-proliferation of keratinocyte. In addition, HA-LCA NPs also down-regulated TNF-α and interferon-gamma-induced expression of pro-inflammatory cytokine genes in keratinocyte cell line. Thus, the skin-permeating HA-LCA NPs may serve as a new therapeutic agent for psoriasis treatment.
more목차
Ⅰ. INTRODUCTION 1
Ⅱ. MATERIALS and METHODS 5
1. Materials 5
2. Preparation and characterization of HA-LCA NPs 6
3. Mice and induction of psoriasis mouse model 7
4. Fluorescence microscopy for the transdermal delivery of HA-LCA NPs 8
5. Histological analysis 9
6. Cells and treatments 9
7. Cell viability test 10
8. RNA extraction and real-time reverse transcription polymerase chain reaction (RT-qPCR) 11
9. Statistical analysis 11
Ⅲ. RESULTS 13
1. Transdermal penetration of HA-LCA NPs in mouse skin 13
2. HA-LCA NPs treatment alleviates psoriatic features in IMQ-induced mouse psoriasis model 18
3. HA-LCA NPs reduces keratinocyte differentiation and immune infiltrates 22
4. Inhibitory effects of HA-LCA NPs on mRNA expression of proinflammatory cytokines in keratinocyte and macrophage cell lines 25
Ⅳ. DISCUSSION 31
Ⅴ. REFERENCE 34
Ⅵ. ABSTRACT IN KOREAN (국문초록) 39
