Solid emulsion gel as a vehicle for delivery of polyunsaturated fatty acids: implications for tissue repair, dermal angiogenesis and wound healing

Abstract

The paper describes preparation and biological characterization of the solid hybrid biomaterial that was designed for cell-targeted lipid delivery in healing tissues. The material referred to as 'solid emulsion gel' combines a protein-stabilized lipid emulsion and a hydrogel structure in a single compartment. The potential of the omega-3 (n-3)-fatty acids rich solid emulsion gel for tissue repair applications was investigated at the macro-, micro-, molecular and gene expression levels, using human fibroblasts and endothelial cells and a porcine model of full-thickness wounds. Being non-cytotoxic in vitro and in vivo, the biomaterial was found to affect cell metabolism, modulate expression of certain genes, stimulate early angiogenesis and promote wound repair in vivo. The neovascular response in vivo was correlated with upregulated expression of the genes involved in lipid transport (e.g. adipophilin), anti-apoptosis (e.g. heat shock proteins, haem oxygenase 1) and angiogenesis (vascular endothelial growth factor, placental growth factor). Collectively, the results of this study provide first evidence that the angiogenic response provided by solid emulsion gel-mediated delivery of n-3 fatty acids is an alternative to the topical administration of exogenous growth factors or gene therapy, and can be advantageously used for the stimulation of tissue repair in complex wounds.

14S,21R-Dihydroxydocosahexaenoic Acid Remedies Impaired Healing and Mesenchymal Stem Cell Functions in Diabetic Wounds

“…The extracts for each sample were pooled together and purified via C18 solid-phase extraction and then analyzed using a LC-UV-MS/MS (LTQ, Thermo, Waltham, MA). The deuterated internal standards added to samples at the time of collection for quantification of interested components were prostaglandin F 2␣ -d 4 14S,21R-diHDHA and 14S,21S-diHDHA were generated by incubating 14S-hydroxy-DHA (14S-HDHA) (50 g) with 1 nmol of human cytochrome P450 mixture (h-P450) (BioCatalytics, Pasadena, CA) at 30°C for 12 h. Under the same condition, 14R,21R-diHDHA and 14R,21S-diHDHA were generated from 14R-HDHA by the h-P450 (11). The h-P450 contains NADPH cofactor, buffer salts, and h-P450 (recombinant human CYP1A2, -2C8, -2C9, -2D6, -2E1, and -3A4) in the company's proprietary ratios.…”

“…The fraction of 14S,21R-diHDHA was dried completely by N 2 gas blower and reconstituted to ethanol. The purified 14S,21R-diHDHA and 14S,21R-diHDHA-d 4 were quantified by LC-UV-MS/MS using NPD1 (10,17-diHDHA, 99% purity) (38) as an internal standard. Additionally, the purified 14S-HDHA-d 5 was quantified by LC-UV-MS/MS using Ϯ14-HDHA (Cayman Chemical) as the standard.…”

“…As shown from our lipidomic analysis, the essential fatty acid docosahexaenoic acid (DHA) 2 is a relatively abundant endogenous lipid component in blood and in wounded full-thickness skin. DHA ameliorates complications of diabetes (3) and significantly promotes wound healing (4). Resolvins, neuroprotectins/protectins, and maresins are lipid mediators (LMs) that are generated naturally from essential -3 fatty acids, DHA, and eicosapentaenoic acid, during acute inflammation and have potent anti-inflammatory functions (5)(6)(7)(8)(9).…”

Cosmetic and Therapeutic Applications of Fish Oil’s Fatty Acids on the Skin

“…It is possible that omega-3 and omega-6 PUFAs modulate or enhance local inflammatory response at wound areas, accelerating the healing rate [98]. Shingel et al [99] described the preparation of a solid emulsion gel for cell-targeted PUFA delivery to skin wounds. The emulsion hydrogel is a combination of a protein-stabilized lipid emulsion and a hydrogel vehicle.…”

Autacoid 14S,21R-Dihydroxy-Docosahexaenoic Acid Counteracts Diabetic Impairment of Macrophage Prohealing Functions

“…9 -11 DHA can also significantly promote wound healing by enhancing angiogenesis. 12 Resolvins, neuroprotectins/protectins, and maresins are lipid mediators generated naturally from DHA during acute inflammation that have potent anti-inflammatory and protective functions. 13,14 Their discovery has opened a new avenue for unraveling the mechanisms behind the beneficial effects of DHA.…”