A surfactant-stripped cabazitaxel micelle formulation optimized with accelerated storage stability.

Pluronic (Poloxomer) micelles can solubilize cabazitaxel (CTX), a second-generation taxane, and then be subjected to low-temperature "surfactant-stripping" to selectively remove loose and free surfactant, thereby increasing the drug-to-surfactant ratio. We previously found that the addition of certain other co-loaded hydrophobic cargo to the micelles can result in stabilized, surfactant-stripped cabazitaxel (sss-CTX) micelles, which resist drug aggregation in aqueous storage, a common challenge for taxanes. Here, we show that elevated temperatures can accelerate the aggregation of sss-CTX micelles, thereby enabling rapid optimization of formulations with respect to the type and ratio of co-loader used for stabilization. A sss-CTX micelle formulation was developed using mifepristone as the co-loader, at a 60% mass ratio to the CTX. Drug release, hemolysis and complement activation were investigated in vitro. Microtubule stabilization and in vitro cytotoxicity were similar for sss-CTX and a conventional Tween-80 micelle formulation. In vivo pharmacokinetics also revealed similar blood circulation of the two formulations. In subcutaneous Lewis lung carcinoma tumors, as well as in an aggressive mouse model of malignant pleural effusion, sss-CTX showed a similar therapeutic effect as the Tween-80 based formulation. Altogether, these data show that sss-CTX can achieve similar efficacy as conventional Tween-80 formulations, albeit with substantially higher drug-to-surfactant ratio and with capability of extended aqueous storage.

Utility of Ultrasonography for Diagnosing and Differentiating Periapical Granuloma from Radicular Cyst.

RATIONALE AND OBJECTIVES: This study aimed to investigate the reliability and accuracy of high-resolution ultrasonography (US) for diagnosing periapical lesions and differentiating radicular cysts from granulomas. MATERIALS AND METHODS: This study included 109 teeth with periapical lesions of endodontic origin from 109 patients scheduled for apical microsurgery. Ultrasonic outcomes were analyzed and categorized after thorough clinical and radiographic examinations using US. B-mode US images reflected the echotexture, echogenicity, and lesion margin, while color Doppler US assessed the presence and features of blood flow of interested areas. Pathological tissue samples were obtained during apical microsurgery and subjected to histopathological examination. Fleiss' κ was used to measure interobserver reliability. Statistical analyses were performed to assess the diagnostic validity and the overall agreement between US and histological findings. The reliability of US compared to histopathological examinations was assessed based on Cohen's κ. RESULTS: The percent accuracy of US for diagnosing cysts, granulomas, and cysts with infection based on histopathological findings was 89.9%, 89.0%, and 97.2%, respectively. The sensitivity of US diagnoses was 95.1% for cysts, 84.1% for granulomas, and 80.0% for cysts with infection. The specificity of US diagnoses was 86.8% for cysts, 95.7% for granulomas, and 98.1% for cysts with infection. The reliability for US compared to histopathological examinations was good (κ = 0.779). CONCLUSION: The echotexture characteristics of lesions in US images correlated with their histopathological features. US can provide accurate information on the nature of periapical lesions based on the echotexture of their contents and the presence of vascularity. It can help improve clinical diagnosis and avoid overtreatment of patients with apical periodontitis.