Over the past few decades, applications of ultrasound (US) in drug delivery have been documented widely for local and site-specific release of bioactives in a controlled manner, after acceptable use in mild physical therapy for tendinitis and bursitis, and for high-energy applications in fibroid ablation, cataract removal, bone fracture healing, etc. US is a non-invasive, efficient, targetable and controllable technique. Drug delivery can be enhanced by applying directed US in terms of targeting and intracellular uptake. US cannot only provide local hyperthermia but can also enhance local extravasations and permeability of the cell membrane for delivery of cell-impermeable and poorly permeable drugs. It is also found to increase the anticancer efficacy of drug against solid tumors by facilitating uniform drug delivery throughout the tumor mass. This review summarizes the mechanism of US; various drug delivery systems like microbubbles, liposomes, and micelles; and biological manifestations employed for improving treatment of cancer, i.e., hyperthermia and enhanced extravasation. Safety issues are also discussed for better therapeutic outcomes of US-assisted drug delivery to tumors. This review can be a beneficial asset to the scientists looking at non-invasive techniques (externally guided) for improving the anticancer potential of drug delivery systems.
Colorectal cancer (CRC) is the third most common cancer of mortality in the world. Chemotherapy based treatment leads to innumerable side effects as it delivers the anticancer drug to both normal cells besides cancer cells. Sonic Hedgehog (SHH), Wnt wingless-type mouse mammary tumor virus/β-catenin, transforming growth factor-β/SMAD, epidermal growth factor receptor and Notch are the main signaling pathways involved in the progression of CRC. Targeted therapies necessitate information regarding the particular aberrant pathways. Advancements in gene therapies have resulted in the recognition of novel therapeutic targets related with these signal-transduction cascades. CRC is a step-wise process where mutations occur over the time and activation of oncogenes and deactivation of tissue suppressor genes takes place. Genetic changes which are responsible for the induction of carcinogenesis include loss of heterozygosity in tumor suppressor genes such as adenomatous polyposis coli, mutation or deletion of genes like p53 and K-ras. Therefore, many gene-therapy approaches like gene correction, virus-directed enzyme-prodrug therapy, immunogenetic manipulation and virotherapy are currently being explored. Development of novel strategies for the safe and effective delivery of drugs to the cancerous site is the need of the hour. This editorial accentuates different novel strategies with emphasis on gene therapy and immunotherapy for the management of CRC.
Several studies have documented the role of hyper-activation of extracellular signal-regulated kinases (ERK) in Autism pathogenesis. Alpha-mangostin (AMG) is a phytoconstituents with anti-oxidants, anti-inflammatory, and ERK inhibition properties in many diseases. Our research aims to investigate the neuroprotective effect of AMG in the rat model of intracerebroventricular-propionic acid (ICV-PPA) induced autism with a confirmation of its effect on the ERK signaling. Autism was induced in Wistar rats (total 36 rats; 18 male/18 female) by multiple doses of PPA through ICV injection for 11 days. Actophotometer and beam walking tasks were used to evaluate animals' motor abilities, and the Morris water maze task was utilized to confirm the cognition and memory in animals. Long term administration of AMG 100 mg/kg and AMG 200mg/kg continued from day 12 to day 44 of the experiment. Before that, animals were sacrificed, brains isolated, morphological, gross pathological studies were performed, and neurochemical analysis was performed in the brain homogenates. Cellular and molecular markers, including ERK, myelin basic protein, apoptotic markers including caspase-3, Bax, Bcl-2, neuroinflammatory markers, neurotransmitters, and oxidative stress markers, have been tested throughout the brain. Thus, AMG reduces the overactivation of the ERK signaling and also restored autism-like behavioral and neurochemical alterations.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.