How to deliver to the dermis: First-in-class dermal delivery technology in human skin.
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Presented by: Park Bo-kyung
Introduction
Many of active compounds for topical therapeutics including cosmetics should deliver to dermis. This is because many skin-related problems, including cosmetic point of view, occur in the dermis. The dermis under the epidermis is a connective tissue composed of collagen, elastic fibers and a mixture of extracellular matrix proteins. Unlike the epidermis, the dermal layer is supplied with blood and lymphatic vessels, nerve endings, fibroblasts and various types of immune cells, so it should be the target of the transdermal delivery system (TDDS). Various TDDS represented by active and passive systems have been intensely researched and the possibility has been reported. However, reach or penetrate the dermis is still challenging. More precisely, few studies have been reported that can deliver cargo to dermis and applied without limitation to the chemical properties or tens of thousands Da or larger or even particles using human model. Therefore, to our knowledge, this is the first study to report that various substances range from small/large size and hydrophobic/ hydrophilic properties and nanoparticle can be delivered to the dermis using a human skin model. This study reports a novel peptide which has capability to deliver to dermis without covalent bond with various cargo and it is demonstrated by confocal microscope. Furthermore, we aimed to demonstrate the mode of action of skin permeation in the stratum corneum (SC) and the epidermis which are skin barriers.
Methods
Skin penetration are evaluated using cadaver skin of full thickness (epidermis, dermis) and measured by confocal microscope system. A novel peptide (INCI: Oligopeptide-191, 12 mer peptide) is prepared using solid-phase-peptide-synthesis. FITC-conjugated collagens of 3 k to 300 kDa and hyaluronic acid of 800 kDa and fluorescently labelled liposome of 200 nm are prepared as a cargo. In order to evaluate the delivery capability of novel peptide, all cargos were divided into two groups, with/without peptide. Section images by confocal are observed 3 hours after cargo treated. To investigate the mechanism of skin permeation the SC and epidermis were peeled off the skin and frozen section slides are prepared.
Results
The study on the skin penetration study, all of cargo with peptide treated group, florescence was observed in dermis. In contrast in the cargo without peptide, was not observed in dermis. The study on delivery capability by cargo size : It has been investigated that novel peptide delivers all different size of cargo to the dermis, from 3 kDa collagen, the smallest size used in the experiment, to 800 kDa hyaluronic acid. In addition, the 200 nm liposome, is known to be the size that can capture dozens of 150 kDa of immunoglobulin, were delivered to the dermis. The study on delivery capability by cargo properties at hydrophilic/ hydrophobic surface: this experiment, novel peptide delivered not only biopolymers closed to hydrophilic but also liposome closed to hydrophobic. The study on pathway of skin permeation: As a result of analyzing the fluorescence of the SC and epidermis treated with hyaluronic acid, it was investigated that it penetrates through intercellular lipid in the SC and it penetrates through intracellular in epidermis.
Discussion
This study aims to report a novel peptide for TDDS and to demonstrate it has a capability to deliver to the dermis in various cargos, and to the human skin model. We used substances of various size ranging from 3 k to 800 kDa and 200 nm of liposome as a cargo, which were also aimed at studying different chemical properties of cargo. (hydrophilic/hydrophobic). In order to investigate the skin penetration pathway, the SC and epidermis were peeled off from skin to analyze by confocal, it was confirmed that cargo penetrates through intercellular lipid in the SC and through intracellular (cell-to-cell) permeation in epidermis. It shows that the novel peptide delivers passed through skin barrier of two different characteristics through self-assembling. This study will contribute to the development of innovative cosmetics that deliver various substances to the dermis. It would be a kind of topical filler that deliver the biopolymers to the dermis with topical treatment and fat reduction technology also the technology that target cells in the dermis such as senolytic.
Many of active compounds for topical therapeutics including cosmetics should deliver to dermis. This is because many skin-related problems, including cosmetic point of view, occur in the dermis. The dermis under the epidermis is a connective tissue composed of collagen, elastic fibers and a mixture of extracellular matrix proteins. Unlike the epidermis, the dermal layer is supplied with blood and lymphatic vessels, nerve endings, fibroblasts and various types of immune cells, so it should be the target of the transdermal delivery system (TDDS). Various TDDS represented by active and passive systems have been intensely researched and the possibility has been reported. However, reach or penetrate the dermis is still challenging. More precisely, few studies have been reported that can deliver cargo to dermis and applied without limitation to the chemical properties or tens of thousands Da or larger or even particles using human model. Therefore, to our knowledge, this is the first study to report that various substances range from small/large size and hydrophobic/ hydrophilic properties and nanoparticle can be delivered to the dermis using a human skin model. This study reports a novel peptide which has capability to deliver to dermis without covalent bond with various cargo and it is demonstrated by confocal microscope. Furthermore, we aimed to demonstrate the mode of action of skin permeation in the stratum corneum (SC) and the epidermis which are skin barriers.
Methods
Skin penetration are evaluated using cadaver skin of full thickness (epidermis, dermis) and measured by confocal microscope system. A novel peptide (INCI: Oligopeptide-191, 12 mer peptide) is prepared using solid-phase-peptide-synthesis. FITC-conjugated collagens of 3 k to 300 kDa and hyaluronic acid of 800 kDa and fluorescently labelled liposome of 200 nm are prepared as a cargo. In order to evaluate the delivery capability of novel peptide, all cargos were divided into two groups, with/without peptide. Section images by confocal are observed 3 hours after cargo treated. To investigate the mechanism of skin permeation the SC and epidermis were peeled off the skin and frozen section slides are prepared.
Results
The study on the skin penetration study, all of cargo with peptide treated group, florescence was observed in dermis. In contrast in the cargo without peptide, was not observed in dermis. The study on delivery capability by cargo size : It has been investigated that novel peptide delivers all different size of cargo to the dermis, from 3 kDa collagen, the smallest size used in the experiment, to 800 kDa hyaluronic acid. In addition, the 200 nm liposome, is known to be the size that can capture dozens of 150 kDa of immunoglobulin, were delivered to the dermis. The study on delivery capability by cargo properties at hydrophilic/ hydrophobic surface: this experiment, novel peptide delivered not only biopolymers closed to hydrophilic but also liposome closed to hydrophobic. The study on pathway of skin permeation: As a result of analyzing the fluorescence of the SC and epidermis treated with hyaluronic acid, it was investigated that it penetrates through intercellular lipid in the SC and it penetrates through intracellular in epidermis.
Discussion
This study aims to report a novel peptide for TDDS and to demonstrate it has a capability to deliver to the dermis in various cargos, and to the human skin model. We used substances of various size ranging from 3 k to 800 kDa and 200 nm of liposome as a cargo, which were also aimed at studying different chemical properties of cargo. (hydrophilic/hydrophobic). In order to investigate the skin penetration pathway, the SC and epidermis were peeled off from skin to analyze by confocal, it was confirmed that cargo penetrates through intercellular lipid in the SC and through intracellular (cell-to-cell) permeation in epidermis. It shows that the novel peptide delivers passed through skin barrier of two different characteristics through self-assembling. This study will contribute to the development of innovative cosmetics that deliver various substances to the dermis. It would be a kind of topical filler that deliver the biopolymers to the dermis with topical treatment and fat reduction technology also the technology that target cells in the dermis such as senolytic.