Dataset Information

Topical Lyophilized Targeted Lipid Nanoparticles in the Restoration of Skin Barrier Function following Burn Wound.

ABSTRACT: Lyophilized keratinocyte-targeted nanocarriers (TLN?) loaded with locked nucleic acid (LNA) modified anti-miR were developed for topical application to full thickness burn injury. TLN? were designed to selectively deliver LNA-anti-miR-107 to keratinocytes using the peptide sequence ASKAIQVFLLAG. TLN? employed DOTAP/DODAP combination pH-responsive lipid components to improve endosomal escape. To minimize interference of clearance by non-targeted cells, especially immune cells in the acute wound microenvironment, surface charge was neutralized. Lyophilization was performed to extend the shelf life of the lipid nanoparticles (LNPs). Encapsulation efficiency of anti-miR in lyophilized TLN? was estimated to be 96.54%. Cargo stability of lyophilized TLN? was tested. After 9 days of loading with anti-miR-210, TLN? was effective in lowering abundance of the hypoxamiR miR-210 in keratinocytes challenged with hypoxia. Keratinocyte uptake of DiD-labeled TLN? was selective and exceeded 90% within 4 hr. Topical application of hydrogel-dispersed lyophilized TLN? encapsulating LNA anti-miR-107 twice a week significantly accelerated wound closure and restoration of skin barrier function. TLN?/anti-miR-107 application depleted miR-107 and upregulated dicer expression, which accelerated differentiation of keratinocytes. Expression of junctional proteins such as claudin-1, loricrin, filaggrin, ZO-1, and ZO-2 were significantly upregulated following TLN?/anti-miR-107 treatment. These LNPs are promising as topical therapeutic agents in the management of burn injury.

SUBMITTER: Li J

PROVIDER: S-EPMC6127501 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Topical Lyophilized Targeted Lipid Nanoparticles in the Restoration of Skin Barrier Function following Burn Wound.

Li Jilong J Ghatak Subhadip S El Masry Mohamed S MS Das Amitava A Liu Yang Y Roy Sashwati S Lee Robert J RJ Sen Chandan K CK

Molecular therapy : the journal of the American Society of Gene Therapy 20180427 9

Lyophilized keratinocyte-targeted nanocarriers (TLNκ) loaded with locked nucleic acid (LNA) modified anti-miR were developed for topical application to full thickness burn injury. TLNκ were designed to selectively deliver LNA-anti-miR-107 to keratinocytes using the peptide sequence ASKAIQVFLLAG. TLNκ employed DOTAP/DODAP combination pH-responsive lipid components to improve endosomal escape. To minimize interference of clearance by non-targeted cells, especially ...[more]

PMID: 29802017

Similar Datasets

Project description:BackgroundExcessive scarring and fibrosis are the most severe and common complications of burn injury. Prolonged exposure to high levels of glucocorticoids detrimentally impacts on skin, leading to skin thinning and impaired wound healing. Skin can generate active glucocorticoids locally through expression and activity of the 11β-hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1). We hypothesised that burn injury would induce 11β-HSD1 expression and local glucocorticoid metabolism, which would have important impacts on wound healing, fibrosis and scarring. We additionally proposed that pharmacological manipulation of this system could improve aspects of post-burn scarring.MethodsSkin 11β-HSD1 expression in burns patients and mice was examined. The impacts of 11β-HSD1 mediating glucocorticoid metabolism on burn wound healing, scar formation and scar elasticity and quality were additionally examined using a murine 11β-HSD1 genetic knockout model. Slow-release scaffolds containing therapeutic agents, including active and inactive glucocorticoids, were developed and pre-clinically tested in mice with burn injury.ResultsWe demonstrate that 11β-HSD1 expression levels increased substantially in both human and mouse skin after burn injury. 11β-HSD1 knockout mice experienced faster wound healing than wild type mice but the healed wounds manifested significantly more collagen deposition, tensile strength and stiffness, features characteristic of excessive scarring. Application of slow-release prednisone, an inactive glucocorticoid, slowed the initial rate of wound closure but significantly reduced post-burn scarring via reductions in inflammation, myofibroblast generation, collagen production and scar stiffness.ConclusionsSkin 11β-HSD1 expression is a key regulator of wound healing and scarring after burn injury. Application of an inactive glucocorticoid capable of activation by local 11β-HSD1 in skin slows the initial rate of wound closure but significantlyimproves scar characteristics post burn injury.

Dataset Information

Topical Lyophilized Targeted Lipid Nanoparticles in the Restoration of Skin Barrier Function following Burn Wound.

Publications

Topical Lyophilized Targeted Lipid Nanoparticles in the Restoration of Skin Barrier Function following Burn Wound.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets