Development and Characterization of Intravenous Nanoemulsions Loaded with Magnolia officinalis Neolignans

Honokiol (HON) and magnolol (MAG), hepatoprotective neolignans from Magnolia spp., are promising candidates for mitigating liver damage associated with long-term parenteral nutrition (PN). However, their clinical use is limited by poor aqueous solubility. This study aimed to develop a multifunctional nanoemulsion platform based on clinically used lipid nanoemulsions (Lipofundin^®/Lipidem^®), enriched with omega-3 fatty acids and loaded with HON, MAG, or a combination of both. Nanoemulsions were prepared using a two-step homogenization process. Pre-emulsions containing HON, MAG, or both neolignans were first obtained using high-shear homogenization, then mixed in a 1:1 volume ratio with Lipofundin or Lipidem and subsequently subjected to high-pressure homogenization. All nanoemulsions met pharmacopeial standards and literature-recommended quality criteria. The formulations showed mean droplet diameters below 500 nm, PFAT5 values below the 0.05% limit, and PDI values < 0.2. Strongly negative zeta potentials (≤-30 mV) confirmed stability. The formulations were non-hemolytic, fully compatible with PN admixtures for 24 h, and non-cytotoxic in THLE-2 cells. Furthermore, all developed nanoemulsions demonstrated lower in vitro hepatotoxicity than clinically used reference formulations, indicating their promising clinical potential. However, further in vivo studies are required to confirm their therapeutic benefits and hepatoprotective effect during parenteral nutrition (PN).