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Areas covered: This comprehensive review deals with the survey, performed through different electronic databases, regarding various challenges and their solutions attained by fabricating delivery systems like nanoparticles, micelle, nanocapsules, nanochannels, and liposomes. It also covers the synthesis of novel LAPA-conjugates for diagnostic purpose.
Expert opinion: Unfortunately, clinical use of LAPA is restricted because of its extensive albumin binding capacity, poor oral bioavailability, and poor aqueous solubility. LAPA is marketed as the oral tablet only. Therefore, it becomes imperative to formulate alternate efficient multiparticulate or nano-delivery systems for administration through non-oral routes, for active/passive targeting, and to scale-up by pharmaceutical scientists followed by their clinical trials by clinical experts. LAPA combinations with capecitabine and letrozole should also be tried for breast cancer treatment. 相似文献
Background
Mast cells and neuroimmune interactions regulate the severity of intestinal radiation mucositis, a dose-limiting toxicity during radiation therapy of abdominal malignancies.Aim
Because endocannabinoids (eCB) regulate intestinal inflammation, we investigated the effect of the cannabimimetic, palmitoylethanolamide (PEA), in a mast competent (+/+) and mast cell-deficient (Ws/Ws) rat model.Methods
Rats underwent localized, fractionated intestinal irradiation, and received daily injections with vehicle or PEA from 1 day before until 2 weeks after radiation. Intestinal injury was assessed noninvasively by luminol bioluminescence, and, at 2 weeks, by histology, morphometry, and immunohistochemical analysis, gene expression analysis, and pathway analysis.Results
Compared with +/+ rats, Ws/Ws rats sustained more intestinal structural injury (p = 0.01), mucosal damage (p = 0.02), neutrophil infiltration (p = 0.0003), and collagen deposition (p = 0.004). PEA reduced structural radiation injury (p = 0.02), intestinal wall thickness (p = 0.03), collagen deposition (p = 0.03), and intestinal inflammation (p = 0.02) in Ws/Ws rats, but not in +/+ rats. PEA inhibited mast cell-derived cellular immune response and anti-inflammatory IL-6 and IL-10 signaling and activated the prothrombin pathway in +/+ rats. In contrast, while PEA suppressed nonmast cell-derived immune responses, it increased anti-inflammatory IL-10 and IL-6 signaling and decreased activation of the prothrombin pathway in Ws/Ws rats.Conclusions
These data demonstrate that the absence of mast cells exacerbate radiation enteropathy by mechanisms that likely involve the coagulation system, anti-inflammatory cytokine signaling, and the innate immune system; and that these mechanisms are regulated by PEA in a mast cell-dependent manner. The eCB system should be explored as target for mitigating intestinal radiation injury. 相似文献Vaccination prevents severe morbidity and mortality from COVID-19 in the general population. The immunogenicity and efficacy of SARS-CoV-2 vaccines in patients with antibody deficiency is poorly understood.
ObjectivesCOVID-19 in patients with antibody deficiency (COV-AD) is a multi-site UK study that aims to determine the immune response to SARS-CoV-2 infection and vaccination in patients with primary or secondary antibody deficiency, a population that suffers from severe and recurrent infection and does not respond well to vaccination.
MethodsIndividuals on immunoglobulin replacement therapy or with an IgG less than 4 g/L receiving antibiotic prophylaxis were recruited from April 2021. Serological and cellular responses were determined using ELISA, live-virus neutralisation and interferon gamma release assays. SARS-CoV-2 infection and clearance were determined by PCR from serial nasopharyngeal swabs.
ResultsA total of 5.6% (n?=?320) of the cohort reported prior SARS-CoV-2 infection, but only 0.3% remained PCR positive on study entry. Seropositivity, following two doses of SARS-CoV-2 vaccination, was 54.8% (n?=?168) compared with 100% of healthy controls (n?=?205). The magnitude of the antibody response and its neutralising capacity were both significantly reduced compared to controls. Participants vaccinated with the Pfizer/BioNTech vaccine were more likely to be seropositive (65.7% vs. 48.0%, p?=?0.03) and have higher antibody levels compared with the AstraZeneca vaccine (IgGAM ratio 3.73 vs. 2.39, p?=?0.0003). T cell responses post vaccination was demonstrable in 46.2% of participants and were associated with better antibody responses but there was no difference between the two vaccines. Eleven vaccine-breakthrough infections have occurred to date, 10 of them in recipients of the AstraZeneca vaccine.
ConclusionSARS-CoV-2 vaccines demonstrate reduced immunogenicity in patients with antibody deficiency with evidence of vaccine breakthrough infection.
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