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  • Chitosan-shelled oxygen-loaded nanodroplets abrogate hypoxia dysregulation of human keratinocyte gelatinases and inhibitors: New insights for chronic wound healing.

Chitosan-shelled oxygen-loaded nanodroplets abrogate hypoxia dysregulation of human keratinocyte gelatinases and inhibitors: New insights for chronic wound healing.

Toxicology and applied pharmacology (2015-05-06)
Amina Khadjavi, Chiara Magnetto, Alice Panariti, Monica Argenziano, Giulia Rossana Gulino, Ilaria Rivolta, Roberta Cavalli, Giuliana Giribaldi, Caterina Guiot, Mauro Prato
RESUMEN

In chronic wounds, efficient epithelial tissue repair is hampered by hypoxia, and balances between the molecules involved in matrix turn-over such as matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are seriously impaired. Intriguingly, new oxygenating nanocarriers such as 2H,3H-decafluoropentane-based oxygen-loaded nanodroplets (OLNs) might effectively target chronic wounds. To investigate hypoxia and chitosan-shelled OLN effects on MMP/TIMP production by human keratinocytes. HaCaT cells were treated for 24h with 10% v/v OLNs both in normoxia or hypoxia. Cytotoxicity and cell viability were measured through biochemical assays; cellular uptake by confocal microscopy; and MMP and TIMP production by enzyme-linked immunosorbent assay or gelatin zymography. Normoxic HaCaT cells constitutively released MMP-2, MMP-9, TIMP-1 and TIMP-2. Hypoxia strongly impaired MMP/TIMP balances by reducing MMP-2, MMP-9, and TIMP-2, without affecting TIMP-1 release. After cellular uptake by keratinocytes, nontoxic OLNs abrogated all hypoxia effects on MMP/TIMP secretion, restoring physiological balances. OLN abilities were specifically dependent on time-sustained oxygen diffusion from OLN core. Chitosan-shelled OLNs effectively counteract hypoxia-dependent dysregulation of MMP/TIMP balances in human keratinocytes. Therefore, topical administration of exogenous oxygen, properly encapsulated in nanodroplet formulations, might be a promising adjuvant approach to promote healing processes in hypoxic wounds.

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Sigma-Aldrich
Ethyl alcohol, Pure, 200 proof, anhydrous, ≥99.5%
Sigma-Aldrich
Ethyl alcohol, Pure, 190 proof, meets USP testing specifications
Sigma-Aldrich
Ethyl alcohol, Pure, 190 proof, ACS spectrophotometric grade, 95.0%
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Ethanol, anhydrous, denatured
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Palmitic acid, ≥99%
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Palmitic acid, BioXtra, ≥99%
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Palmitic acid, ≥95%, FCC, FG
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Palmitic acid, natural, 98%, FG
Supelco
Ethanol standards 10% (v/v), 10 % (v/v) in H2O, analytical standard
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Palmitic acid, ≥98% palmitic acid basis (GC)