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Complications of Intravesical Therapy
Published in Kevin R. Loughlin, Complications of Urologic Surgery and Practice, 2007
Michael A. O’Donnell, José L. Maymí
The anthracycline family includes doxorubicin as well as all its derivatives including epirubicin, pirarubicin, and valrubicin (among others). All of these have been tested as intravesical agents with doxorubicin tested the most, followed by epirubicin and valrubicin. All the members of the anthracycline family are relatively large molecules with molecular weights exceeding 500 Da. Doxorubicin and epirubicin are both 580 Da, while pirarubicin (853 Da) and valrubicin (724 Da) are even larger due to side-chain modifications that affect solubility and biodistribution. Less cardiotoxicity is seen with these derivatives.
Tracking and Imaging
Published in Qiu-Xing Jiang, New Techniques for Studying Biomembranes, 2020
Based on their feature SERS spectra, the investigations on chemical drugs interaction with lipid bilayers or biomembranes were also reported. It is noted that permeability of drugs across biomembrane is related to their efficacy and cytotoxicity.29,30 SERS could provide a better understanding of drug permeation across biomembranes. Because of the cytotoxicity, research on the dynamics of antitumor drugs on membranes is expected to improve treatment efficacy while reducing intracellular accumulation with optimized influx and efflux. Chazalet and colleagues initiated experiments on the behaviors of anthracyclines, chemicals used in chemotherapy, from pirarubicin and to more anthracyclines.31,32 Based on the SERS spectra of anthracyclines and lipid layers, the orientation of anthracyclines in lipid bilayer could be uncovered. Furthermore, based on changes in SERS spectra the difference in behavior of the three anthracyclines was confirmed: pirarubicin could cross the lipid bilayers based on dipalmitoylphosphatidic acid (DPPA) or POPC-DPPA on the surface, while Adriamycin, another anthracycline, would be adsorbed in the second monolayer and thus could not cross the bilayer in the presence of DPPA. Per the composition of lipid bilayers, the behavior of different chemical drugs would be different. Further details will be uncovered in the following work with DPPA, an anionic phospholipid, in a first layer of lipid bilayers could limit the pirarubicin permeation through lipid bilayers.33 Millot and colleagues moved the research of drug behavior from lipid bilayer model to the plasma membrane in living cells. They first investigated the adsorption of mitoxantrone (MTX), an antitumor drug, on the plasma membrane of MTX-sensitive and MTX-resistant cells.34 The SERS intensity of MTX showed the adsorption of MTX on both MTX-sensitive cells and MTX-resistant cells. Further, they investigated the adsorption and permeability of MTX on resistant cells under serial conditions.35
Selecting ideal drugs for encapsulation in thermosensitive liposomes and other triggered nanoparticles
Published in International Journal of Hyperthermia, 2022
Krishna K. Ramajayam, Danforth A. Newton, Dieter Haemmerich
Drug delivery based on IV-DDS depends on the complex interplay between DDS, drugs, and the in situ tumor microenvironment. Computer models can aid in the optimization of DDS and have been used in past studies to compare different TSL formulations and the impact of hyperthermia methods [12,14,18,23,24]. Here, we developed a model that simulates drug delivery based on intravascular triggered release from IV-DDS, such as TSL. To predict the effects of various drugs, we first developed mathematical models that describe the cellular uptake kinetics and cytotoxicity of four anthracycline drugs [doxorubicin (DOX), idarubicin (IDA), pirarubicin (PIR), aclarubicin (ACLA)]. Furthermore, each drug was characterized in three cancer cell lines: angiosarcoma (SVR), Lewis lung carcinoma (LLC), and oral cavity squamous cell carcinoma (SCC-1). We used the Krogh cylinder model, where a representative tumor capillary with surrounding tissue and cancer cells is represented (Figure 1) [25,26]. Importantly, for our computer model, we used in vitro experimentally-determined parameters rather than parameter estimates as is often the case (see Tables 3 and 4).
Advancements in the clinical management of upper tract urothelial carcinoma
Published in Expert Review of Anticancer Therapy, 2019
Jacob Taylor, Xiaosong Meng, Rashed Ghandour, Vitaly Margulis
Unlike for non-muscle invasive bladder cancer, the evidence for intravesical therapy for upper tract disease is far less robust, despite the intravesical recurrence rate of up to 40% after extirpative surgery [72]. In one of the two main prospective clinical trials, O'Brien and colleagues tested single dose post-operative mitomycin C at time of catheter removal versus standard of care in 284 patients and found a 10% less bladder recurrence rate in the mitomycin C group (p = 0.055) [73]. A phase II trial using pirarubicin, another anthracycline agent, reported a bladder recurrence odds ratio of 0.28 (p = 0.023) in the instillation arm compared to standard care at 2 years following RNU [74]. This reduction was larger than in the O'Brien study and is thought to be possibly due to earlier time of instillation, 48 h vs. within 10 days. In light of these early studies, the REBACARE phase II trial evaluating instillation of mitomycin 3 h prior to surgery is recruiting with planned completion in 2021 [75]. Additionally, a larger phase III of pirarubicin within 24 h after surgery is also underway to evaluate recurrence-free survival with a target sample size of 310 patients [76]. Additionally, while trials are in progress to examine the efficacy of intravesical gemcitabine instillation after radical nephroureterectomy to prevent bladder recurrence (NCT03062059), the positive data from the SWOG S0337 trial on intravesical gemcitabine on the prevention of bladder cancer recurrence after transurethral resection of bladder tumor is certainly encouraging, especially given the cheaper cost and less local toxic effects seen with intravesical gemcitabine, which had an adverse event profile similar to placebo [77]. While more level I evidence is necessary, it is clear that peri-operative intravesical therapy is effective in decreasing bladder recurrence.