期刊
COLLOIDS AND SURFACES B-BIOINTERFACES
卷 143, 期 -, 页码 156-167出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.colsurfb.2016.03.036
关键词
Skin delivery; Topical delivery; Skin cancer; Chemoprevention; Ultra deformable nanocarriers; Diindolymethane (DIM); Phytochemicals
资金
- National Institutes of Health's Minority Biomedical Research Support (MBRS)-SC1 program [SC1 GM092779-01]
- National Institute on Minority Health and Health Disparities (NIMHD) P20 program [1P20 MD006738-03]
- Department of Defense (DOD) Breast Cancer Program [W81XWH-11-1-0211]
Purpose: In this study, we developed cationic ultra-flexible nanocarriers (UItraFLEX-Nano) to surmount the skin barrier structure and to potentiate the topical delivery of a highly lipophilic antioxidative diindolylmethane derivative (DIM-D) for the inhibition of UV-induced DNA damage and skin carcinogenesis. Methods: UltraFLEX-Nano was prepared with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, 1,2-dioleoyl-3-trimethylammonium-propane, cholesterol and tween-80 by ethanolic injection method; was characterized by Differential Scanning Calorimetric (DSC), Fourier Transform Infrared (FT-IR) and Atomic Force Microscopic (phase-imaging) analyses and permeation studies were performed in dermatomed human skin. The efficacy of DIM-D-UltraFLEX-Nano for skin cancer chemoprevention was evaluated in UVB-induced skin cancer model in vivo. Results: DIM-D-UItraFLEX-Nano formed a stable mono-dispersion (110.50 +/- 0.71 nm) with >90% encapsulation of DIM-D that was supported by HPLC, DSC, FT-IR and AFM phase imaging. The blank formulation was non-toxic to human embryonic kidney cells. UltraFLEX-Nano was vastly deformable and highly permeable across the stratum corneum; there was significant (p < 0.01) skin deposition of DIM-D for UItraFLEX-Nano that was superior to PEG solution (13.83-fold). DIM-D-UItraFLEX-Nano pretreatment delayed the onset of UVB-induced tumorigenesis (2 weeks) and reduced (p < 0.05) the number of tumors observed in SKH-1 mice (3.33-fold), which was comparable to pretreatment with sunscreen (SPF30). Also, DIM-D-UItraFLEX-Nano caused decrease (p < 0.05) in UV-induced DNA damage (8-hydroxydeoxyguanosine), skin inflammation (PCNA), epidermal hyperplasia (c-myc, CyclinD1), immunosuppression (IL10), cell survival (AKT), metastasis (Vimentin, MMP-9, TIMP1) but increase in apoptosis (p53 and p21). Conclusion: UltraFLEX-Nano was efficient in enhancing the topical delivery of DIM-D. DIM-D-UItraFLEX-Nano was efficacious in delaying skin tumor incidence and multiplicity in SIGH mice comparable to sunscreen (SPF30). (C) 2016 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据