Cancer is a leading cause of death worldwide, and the effectiveness of treatment is consistently not at a satisfactory level. This review thoroughly examines the present knowledge and perspectives of honokiol (HON) in cancer therapeutics. The paper synthesizes critical insights into the molecular mechanisms underlying the observed anticancer effects, emphasizing both in vitro and in vivo studies. The effects of HON application, primarily in the common types of cancers, are presented. Because the therapeutic potential of HON may be limited by its physicochemical properties, appropriate delivery systems are sought to overcome this problem. This review discusses the effect of different nanotechnology-based delivery systems on the efficiency of HON. The data presented show that HON exhibits anticancer effects and can be successfully administered to the site of action. Honokiol exerts its anticancer activity through several mechanisms. Moreover, some authors used the combinations of classical anticancer drugs with HON. Such an approach is very interesting and worth further investigation. Understanding HON’s multiple molecular mechanisms would provide valuable insights into how HON might be developed as an effective therapeutic. Therefore, further research is needed to explore its specific applications and optimize its efficacy in diverse cancer types.

Honokiol (HON) and magnolol (MAG), structural isomers from Magnolia officinalis, exhibit notable anticancer activity, particularly against head and neck squamous cell carcinoma (HNSCC). However, due to their high lipophilicity, their intravenous administration is challenging. This study aimed to develop HON- and MAG-loaded intravenous (IV) nanoemulsions using commercial lipid preparations with varying fatty acid compositions. The formulations were physicochemically characterized and evaluated in vitro using FaDu and SCC-040 HNSCC cell lines. HON and MAG were sterilized via ionizing radiation at doses of 25, 100, and 400 kGy. Their suitability for IV use was assessed through PXRD, DSC, TGA, EPR, FT-IR, NMR, and HPLC analyses. All formulations met safety criteria for IV administration, with mean droplet diameters below 241 nm and encapsulation efficiencies exceeding 95%. They significantly reduced cancer cell viability, with a synergistic effect observed in combined HON and MAG formulations compared to single-compound nanoemulsions. Clinoleic-based formulations showed enhanced anticancer efficacy, likely due to the pro-apoptotic properties of oleic acid. Notably, radiation sterilization at the standard 25 kGy dose preserved the thermal, crystalline, and structural stability of HON and MAG, whereas higher doses (400 kGy) induced degradation. Although free radicals were detected via EPR, their transient nature and rapid decay confirmed the method’s safety. HON/MAG-loaded nanoemulsions exhibited strong anticancer potential, while radiation sterilization at 25 kGy ensured sterility without compromising stability. These findings provide a preliminary in vitro basis for future in vivo studies investigating HON and MAG as potential adjuvant therapies for HNSCC.

(1) Background: Glioblastoma is the most common and aggressive primary brain tumor in adults, with a median survival time for patients treated with standard chemotherapy often of less than 1 year. Potential anticancer activity against glioblastoma is demonstrated by flavonoids, including fisetin (FIS). Although, its clinical application is limited by poor solubility and chemical instability. This study aimed to conduct a preliminary evaluation of fisetin’s suitability for intravenous delivery by developing and characterizing FIS-loaded poly(lactic-co-glycolic acid) nanoparticles (FIS-PLGA-NPs) and assessing their in vitro cytotoxic potential against glioblastoma. (2) Methods: Six FIS-PLGA nanoparticle formulations were prepared via the emulsification–solvent evaporation method and evaluated for key physicochemical properties. The biological activity of fisetin was examined through cell cycle analysis and apoptosis assays, and the most promising formulation was further assessed using an MTT assay in U-138 MG glioblastoma cells. In parallel, pure fisetin was exposed to ionizing radiation, including the standard sterilization dose of 25 kGy, to evaluate its structural stability and suitability for terminal sterilization approaches. (3) Results: The selected formulation (NP4) exhibited a mean particle size of approximately 330 nm, a zeta potential of −7.2 mV, a polydispersity index of 0.25, and high encapsulation efficiency and drug loading of 83.58% and 13.93%, respectively. Despite its preliminary nature, this formulation retained cytotoxic activity in vitro. Moreover, pure fisetin maintained its structural and chemical integrity following radiation exposure, supporting the feasibility of radiation sterilization prior to nanoparticle incorporation. (4) Conclusions: These findings confirm the feasibility of combining radiosterilizable fisetin with PLGA-based nanoencapsulation and provide an initial foundation for the development of an injectable fisetin delivery system for glioblastoma treatment. Further optimization, particularly surface modification, will be required to enhance colloidal stability and systemic performance.

Background/Objectives: Parenteral nutrition (PN) supports patients unable to receive nutrients via the gastrointestinal tract, but it lacks the health-promoting natural bioactive compounds found in a typical oral diet. This study aimed to develop a human serum albumin-based intravenous delivery system for lutein (an antioxidant carotenoid with vision-supportive and hepatoprotective properties) as a PN additive. Methods: An albumin–lutein nanosuspension (AlbLuteN) was synthesized using a modified nanoparticle albumin-bound (nab^TM) technology and characterized physicochemically. The nanoformulation was added to four commercial PN admixtures to assess the supplementation safety throughout the maximum infusion period. Visual inspection and measurements of fat globules larger than 5 µm (PFAT5) and the mean hydrodynamic diameter (Z-average), zeta potential, pH, osmolality, and lutein content were performed to detect potential interactions and evaluate the physicochemical stability. Results: AlbLuteN consisted of uniform particles (Z-average of 133.5 ± 2.8 nm) with a zeta potential of −28.1 ± 1.8 mV, lutein content of 4.76 ± 0.39%, and entrapment efficiency of 84.4 ± 6.3%. Differential scanning calorimetry confirmed the amorphous state of lutein in the nanosuspension. AlbLuteN was successfully incorporated into PN admixtures, without visible phase separation or significant changes in physicochemical parameters. The PFAT5 and Z-average values remained within pharmacopeial limits over 24 h. No substantial shifts in zeta potential, pH, or osmolality were observed. The lutein content remained stable, with losses below 3%. Conclusions: AlbLuteN can be safely added to representative PN admixtures without compromising their stability. This approach offers a novel strategy for intravenous lutein delivery and may contribute to improving the nutritional profile of PN.

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).