Self-assembled hyaluronic acid nanoparticle as a topical agent for psoriasis treatment
- 주제(키워드) psoriasis
- 발행기관 아주대학교
- 지도교수 김욱
- 발행년도 2021
- 학위수여년월 2021. 2
- 학위명 석사
- 학과 및 전공 일반대학원 분자과학기술학과
- 실제URI http://www.dcollection.net/handler/ajou/000000030547
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Self-assembled hyaluronic acid nanoparticles (HA-NPs) are widely used as drug delivery systems because HA has biocompatible, non-toxic, and non-immunogenic. Recently, drug-free HA-NPs have been shown to exert therapeutic effects in type 2 diabetes and atherosclerosis. Here, I investigate the in vitro and in vivo therapeutic efficacy of an empty HA-NP itself in psoriasis, the most common chronic inflammatory skin disease, after topical treatment via transcutaneous delivery. HA-lithocholic acid (LCA) NPs are amphiphilic compounds composed of hydrophilic HA and hydrophobic LCA that self-assemble in an aqueous environment to form sphere-shaped NPs. HA-LCA NPs inhibited the lipopolysaccharide (LPS)-induced polarization of the human monocyte cell line THP-1 into pro-inflammatory M1 macrophages and reduced the expression of interleukin (IL)-23, a key player in psoriasis and inflammatory cascades. In addition, HA-LCA NPs decreased the expression of pro-inflammatory genes in the human keratinocyte cell line HaCaT stimulated with IL-17 and IL-22. Furthermore, transcutaneous administration of HA-LCA NPs resulted in significant localization into the dermis and epidermis in control and imiquimod (IMQ)-induced psoriasis mouse models, thereby effectively ameliorating psoriasis-like skin inflammation as reflected by reduced skin tissue thickening, inflammation, and cytokine expression. These results suggest that skin-penetrating HA-LCA NPs may serve as novel therapeutic agents for the treatment of human psoriasis-like dermatitis by suppressing the inflammatory response.
more목차
Ⅰ. INTRODUCTION 1
Ⅱ. MATERIALS and METHODS 4
1. Materials 4
2. Preparation and characterization of HA-LCA NP 5
3. Cell culture and treatment 6
4. Mice and induction of psoriasis mouse model 7
5. RNA extraction and quantitative real-time polymerase chain reaction (qRT-PCR) analysis 7
6. Cells viability test 8
7. Cell isolation 9
8. FACS analysis 9
9. Western blot 10
10. Franz diffusion cell (FDC) 11
11. Histological analysis 12
12. Statistical analysis 13
Ⅲ. RESULTS 16
1. Synthetic scheme and characteristics of self-assembled HA-LCA NP 16
2. HA-LCA NP inhibits the polarization of resting macrophages into M1 phenotype 20
3. Effects of free HA and LCA on the expression of M1 marker genes in THP-1 cells 26
4. HA-LCA NP inhibits LPS-induced TLR4 signaling pathway in macrophages 31
5. Effects of HA-LCA NP on the expression of psoriasis-related genes in keratinocytes 34
6. Skin-penetrating ability of HA-LCA NP 37
7. Topical treatment of HA-LCA NP alleviates psoriatic symptoms in IMQ-induced psoriasis mouse model 45
8. Topical treatment of HA-LCA NP inhibits keratinocyte hyperproliferation 50
9. Topical treatment of HA-LCA NP decreases infiltration of macrophages into the dermis 53
Ⅳ. DISCUSSION 56
Ⅴ. REFERENCE 60
Ⅵ. ABSTRACT IN KOREAN (국문초록) 65
