Background: Glioblastoma (GBM) is an extremely invasive and heterogenous malignant brain tumor. Despite advances in current anticancer therapy, treatment options for glioblastoma remain limited, and tumor recurrence is inevitable. Therefore, alternative therapies or new active compounds that can be used as adjuvant therapy are needed. This study aimed to develop, optimize, and characterize honokiol-loaded nanoemulsions intended for intravenous administration in glioblastoma therapy. Methods: Honokiol-loaded nanoemulsion was developed by incorporating honokiol into Lipofundin MCT/LCT 20% using a horizontal shaker. The Box–Behnken design, coupled with response surface methodology, was used to optimize the incorporation process. The effect of the developed formulation on glioblastoma cell viability was determined using the MTT test. Long-term and short-term stress tests were performed to evaluate the effect of honokiol on the stability of the oil-in-water system and the effect of different stress factors on the stability of honokiol, respectively. Its physicochemical properties, such as MDD, PDI, ZP, OSM, pH, and loading efficiency (LE%), were determined. Results: The optimized honokiol-loaded nanoemulsion was characterized by an MDD of 201.4 (0.7) nm with a PDI of 0.07 (0.02) and a ZP of −28.5 (0.9) mV. The LE% of honokiol was above 95%, and pH and OSM were sufficient for intravenous administration. The developed formulation was characterized by good stability and a satisfactory toxicity effect of the glioblastoma cell lines. Conclusions: The honokiol-loaded nanoemulsion is a promising pharmaceutical formulation for further development in the adjuvant therapy of glioblastoma.

Flavonols, representing a subclass of flavonoids, are an important group of polyphenols. Their activity is associated with a number of beneficial properties, including hepatoprotective, senolytic, neuroprotective, and anticancer properties. They are found abundantly in many fruits, vegetables, and plant products, but flavonols’ chemistry and structural properties result in their low bioavailability in vivo. In recent years, more and more studies have emerged that aim to increase the therapeutic potential of compounds belonging to this group, including by developing innovative nanoformulations. The present work focuses on the various steps, such as chemical analysis of the compounds, preformulation studies using drug delivery systems, preclinical studies, and finally clinical trials. Each of these elements is important not only for the innovation and efficacy of the therapy but most importantly for the patient’s health. There are also a limited number of studies assessing the population concentration of flavonols in the blood; therefore, this review presents an up-to-date survey of the most recent developments, using the most important compounds from the flavonol group.

Intestinal failure-associated liver disease (IFALD) is a severe liver injury occurring due to factors related to intestinal failure and parenteral nutrition administration. Different approaches are studied to reduce the risk or ameliorate the course of IFALD, including providing omega-3 fatty acids instead of soybean oil-based lipid emulsion or administering active compounds that exert a hepatoprotective effect. This study aimed to develop, optimize, and characterize magnolol-loaded intravenous lipid emulsion for parenteral nutrition. The preformulation studies allowed for chosen oils mixture of the highest capacity of magnolol solubilization. Then, magnolol-loaded SMOFlipid was developed using the passive incorporation method. The Box–Behnken design and response surface methodology were used to optimize the entrapment efficiency. The optimal formulation was subjected to short-term stress tests, and its effect on normal human liver cells and erythrocytes was determined using the MTT and hemolysis tests, respectively. The optimized magnolol-loaded SMOFlipid was characterized by the mean droplet diameter of 327.6 ± 2.9 nm with a polydispersity index of 0.12 ± 0.02 and zeta potential of −32.8 ± 1.2 mV. The entrapment efficiency of magnolol was above 98%, and pH and osmolality were sufficient for intravenous administration. The magnolol-loaded SMOFlipid samples showed a significantly lower toxic effect than bare SMOFlipid in the same concentration on THLE-2 cells, and revealed an acceptable hemolytic effect of 8.3%. The developed formulation was characterized by satisfactory stability. The in vitro studies showed the reduced cytotoxic effect of MAG-SMOF applied in high concentrations compared to bare SMOFlipid and the non-hemolytic effect on human blood cells. The magnolol-loaded SMOFlipid is promising for further development of hepatoprotective lipid emulsion for parenteral nutrition.

Background: Parenteral nutrition (PN) is a lifesaving therapeutic approach for patients unable to meet nutritional needs through oral or enteral routes. Lipid nanoemulsions (NEs), a critical component of PN, provide essential fatty acids and influence the formulation’s physicochemical properties. Advances in drug delivery systems have led to novel intravenous NEs with improved stability, purity, or ability for nutrient/active substance delivery. Due to scattered information and the lack of a standardized protocol for testing intravenous lipid NEs, this study aimed to develop a robust assessment method. The protocol focuses on characterizing the physicochemical properties, stability, and biological efficacy of novel NEs while adhering to bioethical standards. Methods: Four NEs were formulated based on fatty acid profile analysis, and to demonstrate the applicability of our protocol, each NE utilized a distinct emulsifier system. A comprehensive in vitro assessment protocol integrating multiple analytical techniques was employed to evaluate their performance. Results: The mean droplet diameter (MDD) of developed NEs ranged from 180.7 to 185.9 nm, significantly smaller than commercial formulations (249.6–335.4 nm). PFAT5 remained below 0.02%, except for ILE-HS (0.12%), and the zeta potential (ZP) was below −29.8 mV. The freeze–thaw stability constant (K_F) of developed NEs was in the range of commercial formulation, and the sterilization stability constant (K_S) was below 10, except for ILE-HS (23.61 ± 1.65). Injectability tests confirmed that ILE-ELP and ILE-T could be infused at 50 mL/h using an intravenous access with a minimum diameter of 21 G. Hemolytic activity met the strictest criteria (<5%), and MTT assays showed higher cell viability at low concentrations for all NEs except ILE-ELP. Conclusions: The developed five-step protocol provides a unified framework for assessing intravenous lipid NEs, allowing for the selection of NEs with the highest potential for further in vivo assessment.

Curcumin is a well-known and widely used substance of natural origin. It has also been found to be helpful in the treatment of liver diseases. Unfortunately, curcumin has very low bioavailability and a sensitivity to external agents. Improving these parameters is the subject of many studies. One way to overcome these problems may be to use Phosal^® Curcumin as a source of curcumin and encapsulate this dispersion into a nanoemulsion using different types and concentrations of surfactants and co-surfactants, thus manipulating the physicochemical parameters of the nanoemulsion. The present study aimed to develop curcumin-loaded nanoemulsions for intravenous administration and to investigate the effect of Kolliphor HS15 concentration on their critical quality attributes. Methods: Phosal^® Curcumin-loaded nanoemulsions with different concentrations of Kolliphor HS15 were prepared by high-pressure homogenization. The effect of Kolliphor HS15 on emulsion physicochemical properties such as mean droplet diameter (MDD), polydispersity index (PDI), zeta potential (ZP), osmolality (OSM), and pH, as well as encapsulation efficiency (EE) and retention rate (RR) of curcumin, were determined. Mid-term stability studies and short-term stress tests were conducted to evaluate the impact of Kolliphor HS15 on the critical quality attributes of the curcumin-loaded nanoemulsions stored under various conditions. Results: Five nanoemulsions with increasing Kolliphor HS15 concentrations were developed. Their MDD ranged from 85.2 ± 2.0 to 154.5 ± 5.1 nm, with a PDI from 0.18 ± 0.04 to 0.10 ± 0.01 and ZP from −15.6 ± 0.7 to −27.6 ± 3.4 mV. Depending on the concentration of Kolliphor HS15, the EE ranged from 58.42 ± 1.27 to 44.98 ± 0.97%. Conclusions: The studied parameters of the developed nanoemulsions meet the requirements for formulations for intravenous administration. Using the appropriate concentration of Kolliphor HS15 allows for a formulation that presents a protective effect against both curcumin and emulsion degradation.

Fisetin (FIS) is a bioactive flavonoid with antioxidant, anti-inflammatory, and anticancer activity, but its poor aqueous solubility and high lipophilicity limit its therapeutic use. In this study, three-component FIS-loaded mixed micelles based on Poloxamer 407 (P407) or Poloxamer 188 (P188), sodium deoxycholate, and Kolliphor HS15 or Kolliphor ELP were developed and comparatively evaluated. The formulations were prepared by the thin-film hydration method and characterized in terms of physicochemical properties, storage stability, solid-state properties, and in vitro biological activity. All freshly prepared formulations formed nanosized systems with high encapsulation efficiency. Although P188-based micelles showed smaller initial particle sizes, P407-based systems exhibited superior stability after lyophilization and rehydration. Formulations containing Kolliphor ELP showed the most favorable stability profile over 28 days of storage. FT-IR, TG, DSC, and XRPD analyses confirmed successful incorporation of FIS into the polymeric matrix and transformation of the drug into an amorphous or molecularly dispersed state. In vitro studies demonstrated that micellar encapsulation enhanced the cytotoxic activity of FIS against MICH-2 melanoma cells compared with the free compound, while P407-based systems showed a more favorable safety profile toward MRC-5 fibroblasts. These findings indicate that P407-based mixed micelles, particularly those containing Kolliphor ELP, may serve as promising nanocarriers for improving FIS delivery with potential relevance for dermal and anticancer applications.