A pandemic lesson for every CRO: Empower infrastructure to handle crises biopharmadive.com - get the latest breaking news, showbiz & celebrity photos, sport news & rumours, viral videos and top stories from biopharmadive.com Daily Mail and Mail on Sunday newspapers.
A single cellular pathway helps drive almost one in four cancers. After 40 years, scientists may have finally found a way to target the mutant protein that kicks it into overdrive.
Synthetic Oligonucleotides: Regulatory, Analytical & Manufacturing Considerations
By Maura Kibbey, Ph.D., and Nick Healy, U.S. Pharmacopeia (USP)
After decades of investment, research, and development, the therapeutic value of oligonucleotides has started to materialize. Dozens of developers now have dedicated pipelines for diverse indications such as oncology, central nervous system diseases, cardiometabolic disorders, liver diseases, and viral infections, including COVID-19. A search for “oligonucleotide” on ClinicalTrials.gov returned more than 50 active studies. Advances in analytical methods are helping to support these pipelines.
Across the development and release landscapes, methods continue to refine, streamline, and support the development of oligonucleotides from new applications of nuclear magnetic resonance (NMR) spectroscopy that are pushing the boundaries of what can be accomplished in development, to innovative platform approaches for specification and release t
82 and lipid nanoparticles
74 have been developed and used in cancer imaging and diagnosis. During traditional clinical CT imaging, iodinated small molecules and barium sulfate suspensions are usually used as contrast agents,
121,122 but they are not ideal for imaging IBD due to their nonspecificity. Furthermore, when administered orally, these suspensions are nonspecifically distributed throughout the GIT, thus interfering with diagnosis and leading to accumulative radiation exposure in IBD patients.
123 Therefore, the CT contrast agent must not only be stable in the GIT microenvironment but also must be specifically enriched in the diseased parts of the intestine to better detect disease.
Based on the microenvironmental characteristics of the GIT and the design strategy of orally administered DDSs for IBD therapy, the application of nanoparticles may create ideas for the CT imaging in IBD. Naha et al designed and synthesized nanocontrast agents that can be used in the diagnosis
21,22 and photothermal therapy (PTT)
23,24), SDT is featured with sufficient tissue-penetrating depth, high therapeutic efficiency, mitigating side effects and low cost, which makes it specific for treating some patients with tumors in deep positions that are challenging to access surgically.
25,26 The therapeutic mechanism of SDT generally involves the sono-cavitation effect using sonosensitizers and the production of highly toxic reactive oxygen species (ROS), predominantly the singlet oxygen (
1O
2), which kills cancer cells directly by inducing necrosis or apoptosis, also known as immunogenic cell death (ICD), and indirectly by damaging vessels or inhibiting neovascularization in tumor tissues and producing tumor-specific immunity.
21,27,28 Although tumor-associated antigens like peptides or proteins may induce antitumor immune effects under the help of immunologic adjuvants, the existing heterogeneity of patients limits their clinical application.