Self-Surfactant Poly-3hydroxybutyrate-<i>co</i>-3hydroxyhexanoate (PHBHHx) for the Preparation of Usnic Acid Loaded Antimicrobial Nanoparticles Using Nontoxic Chemicals

Polyhydroxyalkanoates (PHAs) are naturally occurring polyesters with promising drug delivery applications. Their hydrophobicity enables lipophilic drug encapsulation, enhancing bioavailability but limiting colloidal stability and physiological compatibility. Surfactants crucially improve the nanoparticle dimensional stability, dispersion, wettability of hydrophobic matrices, and cellular interaction, yet conventional surfactants require additional purification and may pose physiological risks. Self-surfactant systems offer a sustainable alternative. Therefore, this research proposes a green chemical modification of PHAs to develop self-surfactant systems. Hydrophilic groups were introduced onto a poly-3-hydroxybutyrate-<i>co</i>-3-hydroxyhexanoate (PHBHHx) backbone via amidation using choline taurinate ([Ch][Tau]), a biocompatible ionic liquid. This approach eliminates the need for toxic reagents and complex purification. By precisely controlling the PHBHHx/[Ch][Tau] molar ratio, amphiphilic structures with varying hydrophobic tail lengths were produced, as confirmed by infrared spectroscopy and chromatographic analysis. Nanoparticles were fabricated through the emulsion-solvent evaporation method and employed to encapsulate the lipophilic and antimicrobial agent usnic acid. Dynamic light scattering highlighted the obtainment of stable colloidal suspensions with dimensions of 40-160 nm. Biological evaluations demonstrated the antimicrobial efficacy against planktonic <i>S. aureus</i> Newman strain and biofilm inhibition under fluidic conditions even for the unloaded nanoparticles. Additionally, the nanoparticles exhibited no cytotoxicity at concentrations ranging from 10 to 0.1 μg/mL while retaining antimicrobial activity, in contrast to the high cytotoxicity observed for free usnic acid. Overall, this approach offers a sustainable and scalable strategy to produce self-surfactant and intrinsically antimicrobial polymeric nanocarriers suitable for the systemic drug delivery of lipophilic compounds, smart implant coatings, and antibacterial topical formulations.