COMBINATION OF NATURAL OR ENGINEERED PHAGES AND NATURAL BIOACTIVE COMPOUNDS AGAINST STAPHYLOCOCCUS AUREUS ASSOCIATED SKIN ISSUES
Résumé
Introduction: Various skin diseases and cutaneous wound healing failures are associated with microbial dysbiosis and infectious biofilms. Furthermore, the increasing prevalence of multidrug resistant pathogens and the high tolerance of biofilms to antibiotics lead to propose therapeutic alternatives. In this work we propose to combine Nanostructured Lipid Carriers (NLCs) loaded with natural bioactive compounds having pro-healing properties such as curcumin (CUR)[1], with natural or engineered Staphylococcus aureus phages (SaP), as antibiofilm agents, for the prevention and treatment of topical cutaneous health issues.
Materials & Methods and Results: Stable, negatively charged NLCs (80 nm) with an encapsulation efficiency of 85% of curcumin where produced by hot homogenization method and characterized by Dynamic Light Scattering (DLS) and Z-Potential. Natural SaP suspension of 1010 UFP/mL were produced and tittered using the double agar-overlay approach (DAO). The effect of CUR-NLCs on SaP lytic activity was evaluated using several concentrations of actives and evaluated using DAO. Additionally, a CRISPr/Cas9 assisted homologous recombination engineering approach targeting SaP is being implemented.
Conclusion: First results show that the combination of CUR-NLCs and SaP does not impact the infectivity of phages and thus can represent a promising combination strategy for the treatment of skin associated diseases and cutaneous wound.
[1] Calderon-Jacinto R, Matricardi P, Gueguen V, Pavon-Djavid G, Pauthe E, Rodriguez-Ruiz V. Dual Nanostructured Lipid Carriers/Hydrogel System for Delivery of Curcumin for Topical Skin Applications. Biomolecules. 2022 Jun 3;12(6):780. doi: 10.3390/biom12060780. PMID: 35740905; PMCID: PMC9221280.