Antibiotic-LoadedCalcium Crosslinked Alginate WoundDressings Fabricated via Pressurized Gas eXpanded Liquids Technologyin Combination with Supercritical Adsorptive Precipitation for TreatingMethicillin-Resistant Staphylococcus Infections

Antibiotic resistance is a major healthcare challenge globally, and the development of antimicrobial therapies and modes for their targeted delivery is not keeping pace. Many promising antimicrobial candidates are abandoned early in discovery because of their high hydrophobicity and low bioavailability, limiting their evaluation in preclinical models. Therefore, developing drug delivery technologies compatible with potent yet hydrophobic antimicrobial candidates could revitalize a stagnant antibiotic pipeline. Herein, we combined Pressurized Gas eXpanded liquid technology (PGXTEC) with supercritical adsorptive precipitation to load and subsequently deliver poorly water-soluble antimicrobial compounds directly to an infected wound. PGXTEC-processed cross-linked sodium alginate compressed into disks exhibits extremely high specific surface area (∼160 m2/g) to enable drug impregnation and effective exudate absorption. As proof of concept, PGXTEC alginate disks loaded with fusidic acid (FA) suppressed bacterial growth in full thickness wounds infected with methicillin-resistant Staphylococcus aureus (MRSA); furthermore, PGXTEC disks loaded with tigecycline (TIG), typically considered a bacteriostatic antibiotic when used conventionally against MRSA, sterilized wounds with bactericidal activity even at low overall drug doses relative to the conventionally used therapeutic doses for intravenous TIG. PGXTEC combined with adsorptive precipitation is thus a flexible platform technology to deliver hydrophobic antibiotics in a bioavailable format, offering the potential to revive classes of antimicrobial compounds that are excluded early in the discovery process due to low water solubility and incompatible modes of delivery.