Nanomedicine-based drug-delivery systems have significant interest in cancer treatment, such as improving the stabilities and biocompatibilities, precise targeting, and reducing toxicities for non-cancerous cells. Herein, this study presents the synthesis and characterisation of carbonate apatite nanoparticles (nCA) and encapsulated afatinib (AFA) as promising drug delivery candidates for lung cancer treatment. nCA/AFA was synthesised and physicochemically characterised, then the encapsulation capacity, drug loading, and cumulative drug release profile were evaluated. Powder X-ray diffraction (PXRD) confirmed that the synthesised nCA is apatite. Fourier-transform infrared spectroscopy (FTIR) results confirmed the drug loading into the nanoparticles. High-resolution transmission electron microscopy (HR-TEM) determined the morphology of nCA and nCA/AFA and the diameters of 47.36 ± 3.16 and 42.97 ± 2.78 nm, respectively, without an unaltered nCA phase. Encapsulation efficiency (%) and drug loading (%) were 55.08% ± 1.68% and 8.19% ± 0.52%. Brunauer-Emmett-Teller (BET) and dynamic light-scattering (DLS) results revealed that the synthesised nCA is mesoporous, with a surface area of 55.53 m2/g, and is negatively charged. Atomic force microscopy (AFM) showed increasing roughness of nCA/AFA compared to nCA. The drug release from the nano-formulation nCA/AFA demonstrated slow and sustained release compared to the pure drug. Accordingly, nCA/AFA represents a promising drug delivery system for NSCLC treatment.
Several randomized controlled trials (RCTs) evaluated the afatinib efficacy in patients with advanced non-small cell lung cancer (NSCLC) and recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). This review systemically outlined and meta-analyzed the afatinib efficacy in NSCLC and R/M HNSCC in terms of overall survival (OS) and progression-free survival (PFS) endpoints. Records were retrieved from PubMed, Web of Science, and ScienceDirect from 2011 to 2020. Eight afatinib RCTs were included and assessed for the risk of bias. In meta-analysis, overall pooled effect size (ES) of OS in afatinib group (AG) significantly improved in all RCTs and NSCLC-RCTs [hazard ratios (HRs): 0.89 (95% CI: 0.81-0.98, p = 0.02); I2 = 0%, p = 0.71/ 0.86 (95% CI: 0.76-0.97; p = 0.02); I2 = 0%, p = 0.50, respectively]. ES of PFS in AG significantly improved in all RCTs, NSCLC-RCTs, and HNSCC-RCTs [HRs: 0.75 (95% CI: 0.68-0.83; p < 0.00001); I2 = 26%, p = 0.24; 0.75 (95% CI: 0.66-0.84; p < 0.00001); I2 = 47%, p = 0.15/0.76 (95% CI: 0.65-88; p = 0.0004); I2 = 34%, p = 0.0004, respectively]. From a clinical viewpoint of severity, interstitial lung disease, dyspnea, pneumonia, acute renal failure, and renal injury were rarely incident adverse events in the afatinib group. In conclusion, first- and second-line afatinib monotherapy improved the survival of patients with NSCLC, while second-line afatinib monotherapy could be promising for R/M HNSCC. The prospective protocol is in PROSPERO (ID = CRD42020204547).
The immune-modulatory effects of black seeds (Nigella sativa seeds, NSS) are well documented, but the overall in vivo impact of this important natural medicinal product on immune system function has yet to be established. Here we systematically reviewed and meta-analyzed the effects of NSS on humoral [serum titers of immunoglobulins including IgG, IgM, anti-Newcastle virus disease (anti-NDV), and sheep red blood cell antigen (anti-SRBC)] and cellular immunity [total white blood cell (WBC) count and percentages of monocytes, lymphocytes, basophils, neutrophils, and eosinophils] in healthy animals. The PubMed, ScienceDirect, Web of Science, and Scopus databases were searched according to predefined eligibility criteria. Meta-analyses were performed to estimate the final effect size using RevMan software. Seventeen animal studies were eligible for analysis. For humoral immunity, the overall pooled effect size (ES) of NSS on serum titers of IgM and anti-NVD antibodies was not significantly different [mean difference (MD) 75.27, 95% CI: -44.76 to 195.30, p = 0.22 (I2 = 89%, p = 0.003), and -0.01, 95% CI: -0.27 to 0.25, p = 0.94 (I2 = 74%, p = 0.02), respectively]. However, NSS significantly increased serum titers of IgG and anti-SRBC antibodies [MD 3.30, 95% CI: 2.27 to 4.32, p = 0.00001 (I2 = 0%, p = 0.97), and 1.15, 95% CI: 0.74 to 1.56, p = 0.00001 (I2 = 0%, p = 0.43), respectively]. For cellular immunity, the ES of NSS on WBCs, monocytes, and lymphocytes were not significantly different [MD 0.29, 95% CI: -0.55 to 1.13, p = 0.50, (I2 = 14%, p = 0.32), - 0.01, 95% CI: -0.45 to 0.44, p = 0.97 (I2 = 0%, p = 0.77), and 4.73, 95% CI: -7.13 to 16.59, p = 0.43, (I2 = 99%, p = 0.00001), respectively]. In conclusion, black seeds enhance humoral immunity in healthy animals but do not affect cellular immunity.