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e., CHIM). The method successfully quantified >75% of the target DMETs in the trypsin digests of 1 mg tissue homogenate, 15,000 hepatocytes, and 0.06 mg/ml microsomal protein concentration. The precision of DMET quantification measured as the coefficient of variation across different tissue weights, cell counts, or microsomal protein concentration was within 30%. The method confirmed significant extrahepatic abundance of non-cytochrome P450 enzymes such as dihydropyridine dehydrogenase (DPYD), epoxide hydrolases (EPXs), arylacetamide deacetylase (AADAC), paraoxonases (PONs), and glutathione S-transferases (GSTs). The ultrasensitive method developed here is applicable to characterize emerging miniaturized in vitro models and small volume biopsies. In addition, the differential tissue abundance data of the understudied DMETs will be important for physiologically-based pharmacokinetic (PBPK) modeling of drugs.Multivariate model based spectroscopic methods require model maintenance through their lifecycle. A survey conducted by the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) in 2019 showed that regulatory reporting categories for the model related changes can be a hurdle for the routine use of these types of methods. This article introduces industry best practices on multivariate method and model lifecycle management within the Pharmaceutical Quality System. Case studies are provided to demonstrate how the Established Conditions and Post-Approval Change Management Protocol concepts may be leveraged to allow regulatory flexibility for change management and to encourage the use of these techniques for the development and commercialization of pharmaceutical products.Glioma-targeted drug delivery is a hugely challenging task because of the multibarrier in the brain. read more In this study, we report a magnetic T7 peptide&AS1411 aptamer-modified microemulsion for triple glioma-targeted delivery of shikonin and docetaxel (Fe3O4@T7/AS1411/DTX&SKN-M). Such a system comprises two tumor-targeted ligands (T7 peptide and AS1411 aptamer), ultra-small superparamagnetic iron oxide nanoparticle (Fe3O4), and shikonin&docetaxel-coloaded microemulsion (SKN&DTX-M). Fe3O4@T7/AS1411/DTX&SKN-M is capable of stably circulating in the blood, accumulating around the brain under an external magnetic field, distributing inside the glioma via the affinity to nucleolin/transferrin receptor, and retarding the growth of orthotopic glioma. Fe3O4@T7/AS1411/DTX&SKN-M encapsulated Fe3O4 nanoparticles in the core to obtain the superparamagnetism, which did not influence the main surface properties. Introducing 6% (wt%) of DSPE-PEG2000-T7 and 180 nM of AS1411 collaboratively enhanced the murine glioma (G422) cellular uptake of Fe3O4@T7/AS1411/DTX&SKN-M and thereby achieved the strongest antiproliferation among all the groups. Notably, the drug distribution at the brain sites of orthotopic Luc-G422 glioma tumor-bearing nude mice treated with Fe3O4@T7/AS1411/DTX&SKN-M was overwhelming among all the treatments. Most importantly, Fe3O4@T7/AS1411/DTX&SKN-M not only significantly reduced the luminescence signal at the brain areas of orthotopic Luc-G422 glioma mice but also prolonged the overall survival period. The enhancement of anti-glioma efficacy was associated with down-regulating the population of CD133- and CD44-positive cells within the tumors. In summary, such a triple glioma-targeted delivery of shikonin and docetaxel using combinational magnetism and T7/AS1411 modification strategies provides a promising method for synergistic and precise glioma therapy.The SARS-CoV-2 pandemic has provided the stimulus for the rapid development of a variety of diagnostic testing methods. Initially these were deployed as screening tools to evidence spread of the virus within populations. The recent availability of vaccines against the virus and the need to better understand the parameters of post-infection protective immunity requires development of methods, suitable for use in the routine diagnostic laboratory, capable of characterising the viral immune response in greater detail. Such methods need to consider both cellular and humoral immunity. Toward this aim we have investigated use of a commercial multiplex assay (COVID Plus Assay, One Lambda), providing assessment of the SARS-CoV-2 response at structural level, and developed an in-house cell stimulation assay using commercially available viral peptides (Miltenyi). This paper reports our experience in use of these methods in extended investigation of a cohort of healthcare workers with prior screening results indicative of viral infection. The antibody response generated is shown to be both qualitatively and quantitatively different in different individuals. Similarly a recall response to SARS-CoV-2 antigen involving the T cell compartment can be readily demonstrated in recovered individuals but is of variable magnitude.Acute respiratory distress syndrome (ARDS) is a form of oxygenation failure primarily characterized by rapid inflammation resulting from a direct pulmonary or indirect systemic insult. ARDS has been a major cause of death in the recent COVID-19 outbreak wherein asymptomatic respiratory tract infection progresses to ARDS from pneumonia have emphasized the need for a reliable therapy for the disease. The disease has a high mortality rate of approximately 30-50%. Despite the high mortality rate, a dearth of effective pharmacotherapy exists that demands extensive research in this area. The complex ARDS pathophysiology which remains to be understood completely and the multifactorial etiology of the disease has led to the poor diagnosis, impeded drug-delivery to the deeper pulmonary tissues, and delayed treatment of the ARDS patients. Besides, critically ill patients are unable to tolerate the off-target side effects. The vast domain of nanobiotechnology presents several drug delivery systems offering numerous benefits such as targeted delivery, prolonged drug release, and uniform drug-distribution. The present review presents a brief insight into the ARDS pathophysiology and summarizes conventional pharmacotherapies available to date. Furthermore, the review provides an updated report of major developments in the nanomedicinal approaches for the treatment of ARDS. We also discuss different nano-formulations studied extensively in the ARDS preclinical models along with underlining the advantages as well as challenges that need to be addressed in the future.
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