Contrast enhancement agents and radiopharmaceuticals
A Stewart Whitley, Jan Dodgeon, Angela Meadows, Jane Cullingworth, Ken Holmes, Marcus Jackson, Graham Hoadley, Randeep Kumar Kulshrestha in Clark’s Procedures in Diagnostic Imaging: A System-Based Approach, 2020
Selecting the appropriate contrast media to use depends on a number of factors; however, the following molecular characteristics should be considered: Electrically neutral (no charge).Small molecules (low molecular mass).High water solubility.High hydrophilicity.Low molecular toxicity.Low neurotoxicity.
Nanoscale Drug Delivery Vehicles for Solid Tumors: A New Paradigm for Localized Drug Delivery Using Temperature Sensitive Liposomes
Mansoor M. Amiji in Nanotechnology for Cancer Therapy, 2006
Small molecules are on the order of a few nanometers. A liposomal carrier by definition must be larger than the drug it is carrying. Furthermore, a larger liposome can encapsulate a much greater volume, resulting in a higher drug to lipid ratio (for water-soluble drugs).* This is important because an overload of carrier material can impair liver metabolism and phagocytosis (RES uptake) and can cause granulomatous inflammation of the liver. In fact, large doses of empty liposomes were used in the past to block the RES and promote longer liposome-circulation half-lives.55,56Figure 34.3 shows that although only two molecules thick (~ 5 nm), the lipid bilayer† becomes a significant fraction of the total liposome volume at diameters of 200 nm and smaller. For reasons to be later discussed, liposomes are traditionally ~ 100 nm in diameter. At this size, the membrane already takes up 30% of the total liposome volume. Because of mechanical restrictions imposed by membrane thickness and bending stiffness of the lipid bilayer itself (limited curvature), the smallest possible liposome has a diameter of ~ 30 nm, exhibiting a hydrophobic volume fraction of ~ 80% and a limited capacity to carry water soluble drugs
Principles of Radioiodination and Iodine-Labeled Tracers in Biomedical Investigation †
Garimella V. S. Rayudu, Lelio G. Colombetti in Radiotracers for Medical Applications, 2019
The starting material should be of high purity. Trace contaminants are likely to be radioiodinated, sometimes preferentially labeled. Some stabilizing protein, e.g., albumin, could be added after iodination. For most proteins, buffered saline solution is the optimal medium. For small molecules, aqueous or organic solvent in which all the ingredients are soluble could be used. Detergents, for example, Tween® 80, or a solubility enhancer, for example, polyethylene glycol, could be used in the radioiodinizing medium. In enzymatic radioiodination, enzyme inhibitors, thimerosal, or sodium azide should not be present. Overnight dialysis of starting material against several changes of buffer should remove the contaminants. For radioiodination, reductant-free radioiodine must be used. Although sodium bisulfite, thiosulfate, and ethylenediamine-tetraacetate are acceptable as standard preservatives for preventing the oxidation of radioiodide to iodine vapor, such reductants should never be used for iodination because they are difficult to titrate. Radioiodide solutions that have been stocked for more than 2 or 3 weeks contain an unknown amount of iodine vapor, iodate, and periodate and lead to poor yield.
Current status of the development of intravesical drug delivery systems for the treatment of bladder cancer
Published in Expert Opinion on Drug Delivery, 2020
Ho Yub Yoon, Hee Mang Yang, Chang Hyun Kim, Yoon Tae Goo, Myung Joo Kang, Sangkil Lee, Young Wook Choi
Small molecules are molecules with an average molecular weight below 500 Da [127]. Folate is the most widely used ligand owing to the presence of highly upregulated receptors in a wide variety of tumors [127]. Recently, Yoon et al. prepared rapamycin (R)-loaded conventional liposomes (R-CL) and folate-modified liposomes (R-FL) and evaluated their potential to target folate receptor-expressing bladder cancer cells [81]. The in vitro cytotoxic effects of R-FL increased dose-dependently; these liposomes successfully inhibited mTOR signaling and induced autophagy in the bladder cancer cells. In vitro cellular uptake studies using DiI as a model probe revealed that R-FL enhanced the uptake over 2-fold compared to R-CL. For intravesical instillation into an orthotopic mouse model, R-CL and R-FL were dispersed into a P407-gel generating R-CL/P407 and R-FL/P407, respectively. The results showed a significant difference between R-CL/P407 and R-FL/P407, revealing the highest inhibition of tumor growth in the R-FL/P407 group. Increased poly(ADP-ribose) polymerase (PARP) cleavage was also observed in the R-FL/P407 group, indicating apoptosis.
Biosimilars for the treatment of psoriasis
Published in Expert Opinion on Biological Therapy, 2019
Lluís Puig, Anna López-Ferrer
Biologic products are produced using biotechnology methods for in vivo therapeutic uses. They are high molecular weight proteins of biological origin that are highly complex and possess specific tertiary and quaternary structures and a complex biochemical structure giving rise to notorious heterogeneity. These complex proteins need to be produced in living organisms and -generally speaking- cannot be synthesized using chemical manufacturing techniques, as is the case of small-molecule drugs. Biologics used for the treatment of psoriasis are produced using recombinant DNA technology in Chinese hamster ovary mammalian expression systems. Following production in bioreactors, the protein needs to be extracted and purified from cell cultures using complex analytical methods such as chromatographic and filtration techniques to ensure the correct conformation of the protein produced, to remove any contaminants and prevent any contaminating substances form entering the final product, and to ensure that the protein is in the right concentration and solution to prepare it for injection into humans [10]. The complexity of biologic drugs (which in the case of those used for the treatment of psoriasis are immunoglobulins or contain the constant end of IgG) is also derived from posttranslational modifications of proteins, such as glycosylation. Furthermore, every batch of a biologic product consists of multiple variants that may change from batch to batch, increasing the heterogeneity of the protein because biotechnological synthesis is highly process-dependent.
Physician attitudes about non-medical switching to biosimilars: results from an online physician survey in the United States
Published in Current Medical Research and Opinion, 2019
A. Teeple, L.A. Ellis, L. Huff, C. Reynolds, S. Ginsburg, L. Howard, D. Walls, J. R. Curtis
To evaluate the potential implications of NMS to biosimilar products, it is important to consider the differences between small-molecule drugs and biologics. In contrast to traditional small-molecule drugs, biologics are large, complex molecules, produced in living systems, and are often difficult to characterize completely. This makes replication of a biologic product and its manufacturing process much more challenging than that of a small-molecule drug2. As a result, a biosimilar is a product that has been shown to be highly similar to its originator biologic product with no clinically meaningful differences, but it is not identical to the originator biologic. Biosimilars are not considered generics and have a different approval process from that of their originator biologic3. To be designated as interchangeable by the US Food and Drug Administration (FDA), a biosimilar must meet additional requirements beyond biosimilarity. Specifically, it must be demonstrated that the biosimilar is expected to produce the same clinical result as the originator product in any given patient. In addition, the manufacturer must also evaluate the risk of switching between the originator and biosimilar products, in both safety and efficacy4. To date, no biosimilar has been approved as an interchangeable product in the US5.
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