Selective Delivery of Tofacitinib Citrate to Hair Follicles Using Lipid-Coated Calcium Carbonate Nanocarrier Controls Chemotherapy-Induced Alopecia Areata.

Chemotherapy-induced alopecia (CIA) is one of the common side effects in cancer treatment. The psychological distress caused by hair loss may cause patients to discontinue chemotherapy, affecting the efficacy of the treatment. The JAK inhibitor, Tofacitinib citrate (TFC), showed huge potential in therapeutic applications for treating baldness, but the systemic adverse effects of oral administration and low absorption rate at the target site limited its widespread application in alopecia. To overcome these problems, we designed phospholipid-calcium carbonate hybrid nanoparticles (PL/ACC NPs) for a topical application to target deliver TFC. The results proved that PL/ACC-TFC NPs showed excellent pH sensitivity and transdermal penetration in vitro. PL/ACC NPs offered an efficient follicular targeting approach to deliver TFC in a Cyclophosphamide (CYP)-induced alopecia areata mouse model. Compared to the topical application of TFC solution, PL/ACC-TFC NPs significantly inhibited apoptosis of mouse hair follicles and accelerated hair growth. These findings support that PL/ACC-TFC NPs has the potential for topical application in preventing and mitigating CYP-induced Alopecia areata.

Plant-derived extracellular vesicles as a promising anti-tumor approach: A comprehensive assessment of effectiveness, safety, and mechanisms.

BACKGROUND: Plant-derived extracellular vesicles (PDEs) are expected to be a compelling alternative for cancer treatment due to their low cytotoxicity, low immunogenicity, high yield, and potential anti-tumor efficacy. Despite the significant advantages of PDEs, the reliable evidence for PDEs as promising anti-tumor approach remains unsystematic and insufficient. Some challenges remain for the clinical application and large-scale industrial production of PDEs. PURPOSE: Through systematic evaluation and meta-analysis, the objective was to provide scientific, systematic and reliable preclinical evidence to support the clinical use of PDEs in cancer therapy. METHODS: The search for relevant literature, conducted up to March 2024, encompassed various databases including Web of Science, the Cochrane Library, Embase, PubMed, CNKI, Wanfang Data, and the China Science and Technology Journal Database. The SYRCLE´s risk of bias tool was used to assess the methodological quality of the animal studies. For overall effect analysis and subgroup analysis, RevMan 5.4 and Stata 12.0 were utilized. RESULTS: The analysis incorporated a total of 38 articles, comprising 29 in vivo studies and 9 in vitro studies. Meta-analysis indicated that PDEs significantly reduced cancer cell activity and induced apoptosis, reduced tumor volume and tumor weight when used as therapeutic agents, as well as exhibited synergistic anti-cancer via combination therapy. Additionally, PDEs-drugs exerted stronger inhibition of tumor volume compared to the free drug or commercial liposome-drugs. Their therapeutic effects were closely related to regulating tumor cell biological behavior and remodeling the tumor microenvironment. The safety was associated with administration route of PDEs, oral administration was currently preferred until more in-depth studies on the safety of other methods are conducted. CONCLUSIONS: The meta-analysis revealed that PDEs have systematic and reliable preclinical evidence in preclinical studies of cancer therapy, and their efficacy and certain safety could support the clinical application of PDEs in cancer therapy. Of course, further researches are required for large-scale industrial production to meet the needs of clinical applications.

Co-delivery of minoxidil and tocopherol acetate ethosomes to reshape the hair Follicular Microenvironment and promote hair regeneration in androgenetic alopecia.

The most prevalent kind of hair loss is androgenic alopecia (AGA), which is characterized by hair follicle miniaturization and microenvironment dysfunction. Although topical Minoxidil (MXD) was considered to be a safe and effective treatment for AGA, excess reactive oxygen species (ROS) and lower sulfotransferase activity in the hair follicular microenvironment led to an unsatisfactory treatment of AGA. Here, we developed the ethosome (MTE) load of minoxidil and tocopherol acetate to improve the therapeutic effect of MXD on androgenic alopecia. It could regulate the microenvironment around hair follicles, promote the telogen-to-anagen transition of hair follicles, and boost hair regeneration, thus achieving a synergistic effect of 1 + 1 > 2. The results proved that MTE showed excellent stability, biosafety, and good dermal and follicular permeability in vitro. The hair regeneration ability of AGA model mice showed that the co-delivery ethosome might regulate the microenvironment around the hair follicles and improve hair regeneration in comparison to the commercial minoxidil tincture alone. As a result, the strategy provided a promising new strategy for the treatment of AGA.

The Clinical Value of Chemotherapy Combined With Capecitabine in Triple-Negative Breast Cancer-A Meta-Analysis.

Purpose: Triple-negative breast cancer (TNBC) is the most dangerous subtype of breast cancer with high rates of metastasis and recurrence. The efficacy of capecitabine in chemotherapy for TNBC is still controversial. This study evaluated the efficacy and safety of capecitabine combining with standard, adjuvant or neoadjuvant chemotherapy for TNBC. Methods: We systematically searched clinical studies through PubMed, Cochrane library, Embase, Wanfang Database, China Academic Journals (CNKI), and American Society of Clinical Oncology's (ASCO) annual conference report. Studies were assessed for design and quality by the Cochrane risk of bias tool. A meta-analysis was performed using Review Manager to quantify the effect of capecitabine combined with standard, adjuvant or neoadjuvant chemotherapy on the disease-free survival (DFS) rate and overall survival (OS) rate of TNBC patients. Furthermore, safety analysis was performed to evaluate the adverse events. Results: Twelve randomized controlled clinical trials involving totally 4854 TNBC patients were included, of which 2,214 patients received chemotherapy as control group, and 2,278 patients received capecitabine combining with chemotherapy. The results indicated that capecitabine could significantly improve the DFS [hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.71-0.90, P = 0.0003] and OS (HR 0.83, 95% CI 0.74-0.93, P = 0.001). In subgroup analysis, the combination of capecitabine and cyclophosphamide exhibited a significant benefit in all outcomes (DFS HR 0.75, 95% CI 0.63-0.90, P = 0.002; OS HR 0.65, 95% CI 0.52-0.80, p < 0.0001). Additionally, defferent dose of capecitabine subgroup showed same significant effect on the results. Safety analysis showed that the addition of capecitabine was associated with a much higher risk of hand-foot syndrome, diarrhea and mucositis or stomatitis. Conclusion: The results showed that adjuvant capecitabine could bring significant benefits on DFS and OS to unselected TNBC patients, the combination of capecitabine and cyclophosphamide could improve the survival rate of patients, although the addition of capecitabine could bring significant side effects such as hand foot syndrome (HFS) and diarrhea.