repository
펩타이드가 봉입된 가변형 에토좀의 피부투과 개선효과
- Alternative Title
- Transformer-lipid carriers for improving skin delivery of peptide
- Author(s)
- 오가희
- Alternative Author(s)
- Ga-hui Oh
- Advisor
- 박영준
- Department
- 일반대학원 약학과
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2018-02
- Language
- eng
- Keyword
- Palmitoyl pentapeptide; Transformer-Ethosome; Skin permeation; Collagen synthesis; and Deformability
- Alternative Abstract
- The purpose of the present study was to prepare flexible lipid carriers loaded with palmitoyl pentapeptide (PPP) to improve its skin delivery and provide an anti-skin aging effect in the absence of any abnormal skin responses. PPP is a palmitoylated derivative of pentapeptide (Lys-Thr-Thr-Lys-Ser, KTTKS). Palmitoylation provides the peptide with a more desirable partition coefficients, an important consideration for skin absorbance. However, by itself, PPP has limitations with respect to its instability on or in the skin, and has poor penetration and permeation across the skin due to its high molecular weight (802.05 Da), and net charge under the physiological conditions. PPP-loaded conventional liposomes (PPP-CLs), ethosomes (PPP-ESs), and transformer-ethosomes (PPP-TESs) were prepared by a modified extrusion method using phosphatidylcholine (PC) mixed with different ratios of cholesterol or fatty acids. The physicochemical characteristics of palmitoyl pentapeptide-loaded transformer-ethosomes (PPP-TESs) and their skin permeation properties were evaluated. PPP-CLs, PPP-ESs, and PPP-TESs had mean diameters < 150 nm with a homogeneous particle population, a net positive surface charge, and an encapsulation efficiency (EE) of above 97 %. DSC thermograms showed that the incorporation of capric acid (CA), linoleic acid (LA), and myristic acid (MA) into the lipid bilayers altered the transition temperature of the lipid bilayers and also improved the flexibility. The flexibility values of the TESs containing MA, CA, and LA increased in an inverse proportion to the transition temperature of the formulations. Skin permeation of PPP-TESs through both of an artificial membrane and human cadaver skin was much higher than that seen for PPP-CLs and PPP-ESs. In particular, TESs inserted with MA (TESs-MA) was found to be the most effective in improving skin permeation. Moreover, confocal laser scanning microscopy (CLSM) showed that rhodamine-6G-loaded TES-MA (R6G-TES-MA) penetrated into the deeper skin layer. The anti-aging effect of PPP-TES was assessed in normal human dermal fibroblasts (nHDFs) by measuring the mRNA expression of collagen type I alpha 1 chain (COL1A1) and matrix metalloproteinase-1 (MMP-1). nHDFs treated with PPP-lipid carriers had increased type I procollagen level, but decreased MMP-1 levels. In a clinical study, we observed that application of a PPP-lipid carriers solution increased skin elasticity and also decreased facial wrinkles, without abnormal skin responses. These results demonstrated the potential of TESs to enhance skin delivery, indicating that they can provide an anti-skin aging effect both in vitro and in clinical study. Conclusively, TES could be a promising candidate for the transdermal delivery of PPP as well as other drugs.
- Fulltext
- Appears in Collections:
- Graduate School of Ajou University > Department of Pharmacy > 4. Theses(Ph.D)
- Files in This Item:
- There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.
-
- License
- STATISTICS
- Total Visit :3,740,557
- Total Download :1,818
- Today View :18,215
