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Communication Dans Un Congrès Année : 2021

Development of a curcumin loaded-NLCs hydrogel system for topical applications

Résumé

The balance of prooxidant-antioxidant reactions plays a crucial role in the regulation of skin physiologicalprocesses, especially during wound-healing. In standard conditions acute wounds heal in few weeks. However, an uncontroled oxidative stress may hinder the normal wound-healing process by perpetuating tissue damage. Curcumin is a natural active ingredient known by its capacity to efficiently act at the wound site by controlling the toxicity of radicals and through the activation of cytoprotective signaling pathways in dermal cells, thus contributing to the regeneration of the skin barrier function [1]. However, the efficient topical application of active curcumin at cutaneous tissues is hindered by its low solubility in aqueous systems and the need to avoid its degradation (especially by heat and light) during its formulation. In this work, Nanostructured Lipid Carriers (NLCs) [2] were developed as an encapsulating drug system aimed to prevent the drawbacks of curcumin stability and to favor its delivery to the skin. This would allow its topical application at the wound site by being incorporated into a dynamic hydrogel matrix. Experimental Methods NLCs were prepared by the hot homogenization method. Particle size and polydispersity index were determined by Dynamic Light Scattering. Zeta potential was calculated from the electrophoretic mobility obtained from Laser Doppler Micro-electrophoresis. The amount of loaded curcumin was indirectly and directly determined by HPLC and UV-VIS spectrophotometry. In addition, the antioxidant properties of the formulation were assessed by the ABTS assay. The cytocompatibility of the developed nanocariers towards human fibroblasts and keratinocytes was studied by the MTT assay and by the Trypan Blue staining method. Moreover, the amount of curcumin released from NLCs was evaluated at different time points after incubation at 37°C in culture media and in PBS. After the incorporation of the system in a carbopol gel, the flow behaviour of the new composite system was analysed by rheology. Results and Discussion A stable NLCs formulation composed of negatively charged particles of an average size of about 300 nm was obtained. The curcumin encapsulation efficiency was more than 80% and the preservation of the antioxidant properties during the preparation process was demonstrated. The viability of dermal cells involved in the wound-healing process was assessed after 24 hours of contact. Curcumin cytotoxicity was decreased while being encapsulated in the NLCs. Developed NLCs were found to be non toxic to fibroblasts and keratinocytes at concentrations below 0.54 mg/mL (containing 10 μM of curcumin) and 1.1 mg/mL (containing 20 μM), respectively. Furthermore, the formulation showed a prolonged curcumin release profile in biological media, reaching a maximum of 75 % in 72 hours. Finally, NLCs were successfully incorporated into a carbopol hydrogel. Rheological analysis revealed that the mechanical properties of the gel matrix were not disturbed by the addition of NLCs. Overall, our results show the feasibility of combining a natural compound-loaded NLCs and a hydrogel support into a multiscale platform in order to modify the release of the natural compound. Conclusion The developed system is highly compatible and promising for a topical application. Most of all, it preserves the antioxidant properties of curcumin and controls its release towards dermal cells. Such behavior has been demonstrated to be a key feature in order to achieve pro wound-healing effects [3]. Currently, the ability to promote cell migration and proliferation in in-vitro wound-healing tests is under assessment. References [1] Menon, VP, Sudher, AR 2007, ‘Antioxidant and anti-inflammatory properties of curcumin’, Advances in Experimental Medicine and Biology, 105-125, Boston, MA: Springer [2] Müller, RH et al. 2002, ‘Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations’, Advanced Drug Delivery Reviews, S131-S155, Elsevier [3] Demiroic, D et al. 2011, ‘Curcumin induces stress response and hormetically modulates wound healing ability of human skin fibroblasts undergoing ageing in vitro’, Biogerontology, 437–444, Boston, MA: Spriger
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Dates et versions

hal-04449148 , version 1 (09-02-2024)

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  • HAL Id : hal-04449148 , version 1

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Rosa Calderon-Jacinto, Pietro Matricardi, Violeta Rodriguez-Ruiz, Emmanuel Pauthe. Development of a curcumin loaded-NLCs hydrogel system for topical applications. 31st Annual Conference of the European Society for Biomaterials (ESB), ESB, Sep 2021, Porto, France. ⟨hal-04449148⟩
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