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e23561 Background: TGCT/PVNS is an uncommon benign but locally aggressive tumor that affects joints and can lead to significant morbidity. It is characterized in most cases by a t(1;2) translocation that leads to overexpression of colony-stimulating factor 1 (CSF-1) and the accumulation of inflammatory cells that express CSF-1 receptor (CSF-1R) in the affected joints. Imatinib inhibits the tyrosine kinase activity of CSF-1R. Methods: We retrospectively reviewed patients with TGCT/PVNS who received treatment with imatinib within Kaiser Permanente Northern California. Results: Nine patients with relapsed TGCT/PVNS were treated with imatinib from 2019 to 2022. Median age was 43 years. 6 patients were female. The imatinib dose was 400 mg daily. All patients had been treated with surgery previously and relapsed, and further surgery was considered not to be beneficial. All patients presented with persistent joint pain that affected joint mobility and walking. After imatinib therapy was initiated, 7 patients (78%) reported significant improvement in their symptoms, while 2 patients (22%) reported no significant changes. Improvement in symptoms occurred soon after starting therapy, ranging from 3 days to 5 weeks. 8 patients (89%) had stable disease by RECIST criteria based on MRI, and 1 patient was not evaluable. 5 patients are still receiving imatinib currently. The longest treatment duration is 27 months. 4 patients required a dose reduction secondary to toxicity, and 3 patients discontinued therapy (2 patients with G3/4 hepatotoxicity and 1 patient self-discontinued treatment). 2 patients who discontinued imatinib continue to experience resolution of joint pain and other symptoms 10 and 24 months later respectively. Conclusions: Our study shows that treatment with imatinib can result in rapid and lasting symptomatic improvement in patients with relapsed TGCT/PVNS, even after treatment discontinuation. This suggests that imatinib can be an effective and safe treatment option for patients with relapsed TGCT/PVNS refractory or not amenable to further surgery.

Zicao is a traditional Chinese herbal medicine that has been used for the topical treatment of wounds in the form of oil-based ointment for several hundred years. To overcome the disadvantages of oil-based ointment such as irritation, discomfort, and difficulty in cleaning, this study developed a water-based topical formulation of Zicao. An ethanol extract of Zicao was included in 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) to form a water-soluble Zicao-HP-β-CD complex. The formation of the Zicao-HP-β-CD complex was determined using LC-MS, 1H NMR, ROSEY, and solubility analysis. The bioactivity of Zicao-HP-β-CD complex in aqueous solution was evaluated using cellular uptake in vitro and experimental excision wounds in vivo. The LC-MS, 1H NMR, ROESY, and solubility analyses results show that Zicao extract was successfully included by the HP-β-CD. The results of the cellular uptake in vitro and wound healing in vivo suggest that the effect of Zicao was enhanced following the formation of the Zicao-HP-β-CD complex. Therefore, we concluded that complexation with HP-β-CD might provide a potential method for developing an effective water-based topical solution of Zicao.

Minoxidil dissolved in organic solvents is commonly used in the treatment of androgenic alopecia because it is hydrophobic and poorly soluble in water. The aim of this investigation was to develop an aqueous minoxidil solution without addition of organic solvents. To this end, minoxidil was encapsulated in 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) to form a minoxidil–HP-β-CD inclusion complex with aqueous solubility higher than that of pure minoxidil. Minoxidil–HP-β-CD inclusion complexes were prepared using a freeze-drying method from minoxidil and HP-β-CD at a molar ratio of 1:1. Complex formation was confirmed by nuclear magnetic resonance, thermogravimetric analysis, and thin layer chromatography. The structure of the complex was determined using two-dimensional rotating frame overhauser effect spectroscopy. Minoxidil–HP-β-CD inclusion complexes were dissolved in water to form a homogeneous aqueous solution, and its effect on the hair cycle of mice was evaluated in vivo. The results support the feasibility of using HP-β-CD to prepare an aqueous minoxidil solution to replace organic solvent-based solutions.

Ferulic acid (FA) belongs to the family of phenolic acids and exhibits a wide variety of biological activities. However, the bioavailability of FA is not optimal, owing to its limited aqueous solubility. Several methods have been developed to increase FA bioavailability and enhance its cytoprotective effects. Complexing FA with cyclodextrins (CDs) may provide an alternative method to approach these goals. In this study, we prepared an FA-2-hydroxypropyl-β-CD (FA-HP-β-CD) complex, at a 1:1 M ratio of FA to HP-β-CD, which was characterized by 1H NMR, two-dimensional rotating frame spectroscopy and differential scanning calorimetry. Aqueous solubility of FA was improved after complexing with HP-β-CD. Furthermore, in vitro and in vivo experimental results indicated that the FA-HP-β-CD complex had greater bioactivity than FA alone. Therefore, we can conclude that the limitations of FA usage due to low aqueous solubility and bioavailability can be overcome by creating an HP-β-CD inclusion complex with the hydrophobic FA.

β-Sitosterol (Sit) has been used as a functional food additive. Among its many beneficial effects, this phytosterol plays a role in controlling obesity by inhibiting the adipogenesis process of pre-adipocytes. However, the highly lipophilic character of Sit limits its bioavailability. In the present study, 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) was used to form a complex with Sit, namely the Sit-HP-β-CD inclusion complex, and the inhibitory effect of this complex on adipogenesis in the 3T3-L1 pre-adipocyte cell line was investigated. The results of DSC, TLC, 1H NMR spectroscopy, and 2D ROESY showed that the Sit-HP-β-CD inclusion complex was successfully synthesized. In addition, the inhibitory effect of the Sit-HP-β-CD inclusion complex on adipogenesis was evaluated using the Oil Red O staining method and western blot analysis after a 14-day adipogenesis induction in 3T3-L1 pre-adipocytes. The results showed that the Sit-HP-β-CD inclusion complex had a higher efficiency than Sit in reducing intracellular lipid accumulation and the expression levels of PPARγ and FAS in 3T3-L1 cells, suggesting that the inhibitory effect on adipogenesis was improved by the formation of the Sit and HP-β-CD complex.

Rhubarb is a traditional Chinese medicinal herb, and the ethanolic extract of rhubarb consists of active anthraquinones, which are hydrophobic and have antiproliferative effects on hepatoma cell lines. To increase the aqueous solubility of rhubarb and study the consequent bioavailability, the ethanolic extract of rhubarb was complexed with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), a cyclic oligosaccharide that has a hydrophilic outer surface and a hydrophobic central cavity, to form a rhubarb-HP-β-CD complex. This complex was characterized by performing nuclear magnetic resonance spectroscopy, two-dimensional rotating frame spectroscopy and thin layer chromatography to confirm the inclusion of anthraquinones from rhubarb extract in HP-β-CD (weight ratio of rhubarb extract:HP-β-CD=1:9). We investigated the effects of complexing rhubarb extract with HP-β-CD on the growth of Huh7 and HepG2 cells by performing cytotoxicity analysis, cellular uptake test, and colony formation assay. Our results showed that complexation of rhubarb extract with HP-β-CD increased the aqueous solubility and bioavailability of rhubarb and thus enhanced its effect on hepatoma cells.