HPLC-UV and LC-MS/MS analysis to study formulation and long-term stability of some anticancer drugs in elastomeric pumps

Drug stability evaluations in elastomeric pump represent the first step to certify the safety of a therapeutic treatment in oncology. Since the stability of several anticancer molecules is due to their reactivity and stability in elastomeric pumps, made up of different materials, several experimental conditions, such as temperature, pH, concentration and possible chemical interactions among drugs in a single formulation, should be always investigated. Galenic preparation of anticancer drugs is an important prerogative of Anticancer Units within hospital pharmacies and, considering the burden of COVID-19 pandemic event, specific guidelines for therapeutic administration in elastomeric pumps reducing hospitalization both for post-surgical treatment and for therapeutic treatment have been worldwide elaborated. In the present study, the stability of Doxorubicin and Vincristine as a single formulation at different experimental conditions has been investigated. Moreover, we report a systematic study of 5-FU, which is known to be largely used in these medical devices, although its criticisms in terms of solubility, pH effect, storage time and conditions. Our results demonstrate that doxorubicin and vincristine can be mixed safely as a single formulation and 5-FU is stable for 32 days at different temperatures and concentrations in elastomeric pumps

Selective sigma-2 ligands preferentially bind to pancreatic adenocarcinomas: applications in diagnostic imaging and therapy

<p>Abstract</p> <p>Background</p> <p>Resistance to modern adjuvant treatment is in part due to the failure of programmed cell death. Therefore the molecules that execute the apoptotic program are potential targets for the development of anti-cancer therapeutics. The sigma-2 receptor has been found to be over-expressed in some types of malignant tumors, and, recently, small molecule ligands to the sigma-2 receptor were found to induce cancer cell apoptosis.</p> <p>Results</p> <p>The sigma-2 receptor was expressed at high levels in both human and murine pancreas cancer cell lines, with minimal or limited expression in normal tissues, including: brain, kidney, liver, lung, pancreas and spleen. Micro-PET imaging was used to demonstrate that the sigma-2 receptor was preferentially expressed in tumor as opposed to normal tissues in pancreas tumor allograft-bearing mice. Two structurally distinct sigma-2 receptor ligands, SV119 and WC26, were found to induce apoptosis to mice and human pancreatic cancer cells <it>in vitro </it>and <it>in vivo</it>. Sigma-2 receptor ligands induced apoptosis in a dose dependent fashion in all pancreatic cell lines tested. At the highest dose tested (10 μM), all sigma-2 receptor ligands induced 10–20% apoptosis in all pancreatic cancer cell lines tested (p < 0.05). In pancreas tumor allograft-bearing mice, a single bolus dose of WC26 caused approximately 50% apoptosis in the tumor compared to no appreciable apoptosis in tumor-bearing, vehicle-injected control animals (p < 0.0001). WC26 significantly slowed tumor growth after a 5 day treatment compared to vehicle-injected control animals (p < 0.0001) and blood chemistry panels suggested that there is minimal peripheral toxicity.</p> <p>Conclusion</p> <p>We demonstrate a novel therapeutic strategy that induces a significant increase in pancreas cancer cell death. This strategy highlights a new potential target for the treatment of pancreas cancer, which has little in the way of effective treatments.</p

Nuclear Medicine Imaging Tracers for Neurology

Tracers to investigate neurological disorders with positron emission tomography (PET) or single-photon emission computed tomography (SPECT) have found many applications. Several molecular targets can be studied in the human brain in vivo, both in health and disease. Initially, most attention was given to tracers for translocator protein (TSPO), deposition of beta-amyloid, and the dopaminergic system. Many clinical studies have been published with application of a variety of tracers for these targets. During the past few years, more tracers have reached the stage of human studies such as imaging agents for tau protein, P2X7 receptor, SV2A receptor, and the cholinergic system. Other targets of interest that have been studied in man to a lesser extent are N-methyl-d-aspartic acid (NMDA), serotonergic, adenosine, gamma-aminobutyric acid (GABA), sigma, opioid, and metabotropic glutamate subtype 5 (mGlu5) receptors. In addition, several transporter systems have received a great deal of attention. Many tracers for new molecular targets are under development and may open new horizons in the future. Most PET tracers for the brain were initially labeled with 11C but were later replaced by 18F-labeled analogs, since this radionuclide enables longer scanning protocols, dissemination to other hospitals, and commercialization. This initial chapter will highlight PET tracers that have already reached the state of human application.</p

An updated patent review on P-glycoprotein inhibitors (2011-2018)

Introduction: P-glycoprotein is a complex ATP-ase transporter involved in physiological and pathological functions. In particular, it is involved in the onset of multidrug resistance in cancer, in ocular disease, Chronic Rhinosinusitis, CNS diseases such as Alzheimer, Parkinson, and epilepsy. One of the aims of clinicians and pharmacologists is to monitor P-gp activity through the inhibitors and to use its activity and/or expression in physiological barriers for the early diagnosis of several pathologies. Considering P-glycoprotein activity, several substrates have been characterized but the challenge is to design ‘pure’ P-glycoprotein inhibitors. Area covered: P-glycoprotein inhibitors display a large spectrum of activities. Here the contents of patents focused on the role of P-glycoprotein inhibitor in modulating MDR in cancer, in bioavailability, in ocular disease and Chronic Rhinosinusitis are reported. Expert opinion: the use of P-glycoprotein inhibitor sic et simpliciter, or in coadministration with therapeutic agents, for ocular disease, and Chronic Rhinosinusitis is promising and could be suggested for additional trials. By contrast, the bioavailability of the coadministrated drugs, increased by P-glycoprotein inhibitor, deserves a wider discussion, in particular on the pharmacokinetic aspect of both P-glycoprotein inhibitor and the coadministered drug

ABC pumps and their role in active drug transport

Pharmacokinetic limitations affect drug bioavailability determining the loss or the reduction of the pharmacological effects. The Gastro Intestinal tract (GI) and the Blood Brain Barrier (BBB) are the most important restrictive and selective physiological lines of defense of the organism. Although several parameters such as LogP, LogD and K(a) have been extensively employed for determining drug bioavailability, the active transports, present in these biological barriers, play an important role for dosing and limiting cell drugs concentration. In particular, ATP Binding Cassette (ABC) transporters are involved in the active transport both in GI and BBB. Their strategic activity and biochemical and pharmacological role are herein treated

Activatable fluorescent probes: a new concept in optical molecular imaging

Activatable fluorescent probes share the unique feature of being turned on only under specific conditions: they are &quot;silent&quot; when not interacting with a specific target protein, microenvironment, or reactive species. Several activatable fluorescence probes have demonstrated their potential in cell biology study, disease study and diagnosis, and even in the rapidly expanding field of image-guided surgery. In this review, we will summarize progress in the design of activatable probes and their application in studying cell biology or in optical imaging. Some of the most effective examples of activatablefluorescent probes will be resented and their application will be discussed