In Vivo Evaluation of Almotriptan malate Formulation through Intranasal Route for the Treatment of Migraine: Systematic Development and Pharmacokinetic Assessment.

Migraine headaches are usually intolerable, and a quick-relief treatment remains an unmet medical need. Almotriptan malate is a serotonin (5-HT1B/1D) receptor agonist approved for the treatment of acute migraine in adults. It is currently available in an oral tablet dosage form and has a Tmax of 1-3 h, and therefore, there is a medical need to develop a non-invasive rapidly acting formulation. We have developed an intranasal formulation of almotriptan malate using the quality-by-design (QbD) approach. A 2-factor 3-level full factorial design was selected to build up the experimental setting. The developed formulation was characterized for pH, viscosity, in vitro permeation, ex vivo permeation, and histopathological tolerance. To assess the potential of the developed formulation to produce a rapid onset of action following intranasal delivery, a pharmacokinetic study was performed in the Sprague-Dawley rat model and compared to the currently available marketed oral tablet formulation. For this, the LC-MS/MS bioanalytical method was developed and used for the determination of plasma almotriptan malate concentrations. Results of a pharmacokinetic study revealed that intranasal administration of optimized almotriptan malate formulation enabled an almost five-fold reduction in Tmax and about seven-fold increase in bioavailability in comparison to the currently available oral tablet formulation, suggesting the potential of developed almotriptan malate intranasal formulation in producing a rapid onset of action as well as enhanced bioavailability.

Bugs as Drugs: Understanding the Linkage between Gut Microbiota and Cancer Treatment.

The commensal microbiota is known to regulate host physiology. Dysbiosis or compromised resilience in the microbial ecology is related to the impending risk of cancer. A potential link between cancer and microbiota is indicated by a lot of evidence. The current review explores in detail the various links leading to and /or facilitating oncogenesis, providing sound reasoning or a basis for its utilization as potential therapeutic targets. The present review emphasizes the existing knowledge of the microbiome in cancer and further elaborates on the factors, like genetic modifications, effects of dietary components, and environmental agents, that are considered to assess the direct and indirect effect of microbes in the process of oncogenesis and on the host's health. Strategies modulating the microbiome and novel biotherapeutics are also discussed. Pharmacomicrobiomics is one such niche accounting for the interplay between the microbiome, xenobiotic, and host responses, which is also looked upon. The literature search strategy for this review was conducted by following the methodology of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). The method includes the collection of data from different search engines, like PubMed, ScienceDirect, SciFinder, etc., to get coverage of relevant literature for accumulating appropriate information regarding microbiome, cancer, and their linkages. These considerations are made to expand the existing literature on the role of gut microbiota in the host's health, the interaction between host and microbiota, and the reciprocal relationship between the microbiome and modified neoplastic cells. Potential therapeutic implications of cancer microbiomes that are yet unexplored and have rich therapeutic dividends improving human health are discussed in detail in this review.