The Efficacy and Safety of Teprotumumab in Thyroid Eye Disease: Evidence from Randomized Controlled Trials.

In this study, we conducted a meta-analysis to assess the efficacy and safety of teprotumumab in treating thyroid eye disease. We searched the Cochrane Library, PubMed, and Embase databases from inception to May 25, 2022, and included all randomized controlled trials. Odds ratios (ORs) were calculated using fixed- or random-effect models. A total of three studies involving 341 patients were identified. Overall, the analysis revealed that teprotumumab demonstrated superior integrated proptosis response compared to placebo in both the intention-to-treat (ITT) population (OR = 17.81, 95% CI = [10.32, 30.76], I2 = 50%) and per-protocol population (OR = 24.53, 95% CI = [12.96, 46.45], I2 = 14%). Furthermore, patients receiving teprotumumab showed significant improvement in overall response (OR = 8.35, 95% CI = [4.74, 14.71], I2 = 79%), diplopia response (OR = 5.53, 95% CI = [3.24, 9.44], I2 = 0%), and achieving a clinical activity score (CAS) of 0 or 1 (OR = 6.26, 95% CI = [3.87, 10.12], I2 = 0%). Moreover, patients treated with teprotumumab experienced greater improvements in proptosis (MD = -2.49, 95% CI = [-2.54, -2.45], I2 = 98%) and Graves' ophthalmopathy-specific quality of life (GO-QOL, MD = 11.48, 95% CI = [11.03, 11.93], I2 = 95%). However, it is important to note that patients receiving teprotumumab had a higher risk of adverse events, including serious adverse events, gastrointestinal adverse reactions, and muscle spasms. In summary, teprotumumab demonstrated greater improvement in proptosis response, proptosis, diplopia response, overall response, GO-QOL, and CAS. Nonetheless, it should be considered that its use is associated with a higher risk of adverse events.

Ascorbic Palmitate as a Bifunctional Drug and Nanocarrier of Paclitaxel for Synergistic Anti-Tumor Therapy.

The in vivo application of ascorbate is currently limited by the very high blood concentrations that are required to achieve therapeutic levels in tumors, which needs to exploit a novel drug platform to improve the pharmacokinetics of vitamin C (Vc) and its antitumoral effects. In this study, ascorbyl palmitate (AP), an amphiphilic molecule, is the palmitate acid ester derivative of ascorbic acid, which can be formed a "bifunctional" nanoparticle in which the AP acts not only as an antitumor drug but also as a nanocarrier for encapsulating hydrophobic antitumor drugs such as paclitaxel (PTX). We developed a bifunctional nanocarrier based on AP, which loaded with PTX for synergistic cancer chemotherapy. The resulting PTX-AP nanoparticles (PTX-APNPs) were spherical and had an average size of 294.2 nm based on dynamic light scattering. The in vitro anti-B16F10 cells test of PTX-APNPs revealed an obvious synergistic effect of AP and PTX, and the PTX-APNPs strongly induced cell apoptosis and production of reactive oxygen species. In addition, PTX-APNPs formulation also effectively suppressed the tumorigenicity of B16F10 cells in female C57BL/6 mice without causing severe toxicity. These results suggest that AP-based nanoparticles formulated with paclitaxel are useful for synergistic chemotherapy.

Ascorbyl palmitate-incorporated paclitaxel-loaded composite nanoparticles for synergistic anti-tumoral therapy.

A co-loaded drug delivery system based on ascorbyl palmitate that can transport various functional drugs to their targets within a tumor represents an attractive strategy for increasing the efficiency of anticancer treatment. In this study, we developed a dual drug delivery system to encapsulate ascorbyl palmitate (AP) and paclitaxel (PTX) for synergistic cancer therapy. AP, which is a vitamin C derivative, and PTX were incorporated into solid lipid nanoparticles (AP/PTX-SLNs), which were used to treat murine B16F10 melanoma that had metastasized to the lungs of mice. These nanoparticles were spherical with an average size of 223 nm as measured by transmission electron microscope and dynamic light scattering. In vitro cytotoxicity assays indicated that the AP/PTX-SLNs with an AP/PTX mass ratio of 2/1 provided the optimal synergistic anticancer efficacy. In vivo, AP/PTX-SLNs were revealed to be much more effective in suppressing tumor growth in B16F10-bearing mice and in eliminating cancer cells in the lungs than single drug (AP or PTX)-loaded SLNs via a synergistic effect through reducing the Bcl-2/Bax ratio. Furthermore, no marked side effects were observed during the treatment with the AP/PTX-SLNs, indicating that the co-delivery system with ascorbyl palmitate holds promising clinical potential in cancer therapy.