Potential of Newly Synthesized Sea Buckthorn Phytocarriers as Anti-Inflammatory Active Agents

<b>Background:</b> Phytocarriers are advanced drug delivery systems that use biocompatible and biodegradable materials to enhance the efficacy, stability, and bioavailability of natural products. The sea buckthorn (<i>Hippophae rhamnoides</i> L.) berry extract is rich in essential fatty acids and antioxidants, including vitamin C, vitamin E, and anthocyanins, which contribute to its wide-ranging health benefits. In this study, we assessed the morphology, intracellular delivery, and anti-inflammatory effect of sodium cholate (NaC) and sodium deoxycholate (NaDC)-based phytocarriers loaded with ethanolic extract from sea buckthorn berries (sea buckthorn carrier nanostructures, further defined as phytocarriers). <b>Methods:</b> Negative and electron cryo-microscopy were used to analyze hollow and loaded nanocarriers. The cyto-compatibility of nanocarriers was assessed by endpoint (LDH and MTS) and real-time cell assays, on both human fibroblasts (HS27) and human normal monocytes (SC). The anti-inflammatory effect of hollow and loaded nanocarriers was tested by multiplexing. <b>Results:</b> The negative and electron cryo-microscopy analyses showed that NaC-based phytocarriers were spherical, whilst NaDC-based phytocarriers were predominantly polymorphic. Moreover, the NaDC-based phytocarriers frequently formed large lipid networks or "plaques". Although 24 h cytotoxicity testing showed both types of nanocarriers are biocompatible with human fibroblasts and monocytes, based on a long-term real-time assay, NaDC delayed fibroblast proliferation. NaC sea buckthorn phytocarriers did not impair fibroblast proliferation in the long term and they were uptaken by cells, as shown by hyperspectral microscopy. NaC nanocarriers and NaC sea buckthorn phytocarriers induced an anti-inflammatory effect, lowering IL-8 cytokine production in normal human monocytes as soon as 4 h of treatment lapsed. <b>Conclusions:</b> NaC-derived phytocarriers loaded with sea buckthorn alcoholic extract are a cell-compatible delivery system with anti-inflammatory properties.