Current Drug Metabolism - Volume 21, Issue 11, 2020

Background: Cytochrome P450 (CYP450) enzymes play an important role in the metabolism of 70-80% of the currently used medications, including proton pump inhibitors. There are some data analyzing the impact of gene polymorphisms of CYP450 enzymes on most widely used PPIs, such as omeprazole, however, the data on pantoprazole are highly lacking. Objective: To summarize the most recent publications and studies on the role of polymorphisms of the genes encoding CYP450 enzyme 2C19 in the metabolism of pantoprazole and pantoprazole based Helicobacter pylori eradication regimens. Methods: We performed a non-systematic search of the available literature on the selected topic. Results and Conclusion: The data on cytochrome P450 gene polymorphisms and their role in pantoprazole metabolism and pantoprazole based Helicobacter pylori eradication remain conflicting. Individual differences in pantoprazole metabolism might be partly related to genetic polymorphisms of CYP450 enzymes. Most of the studies support the observation that cytochrome 2C19 polymorphisms have an impact on the pharmacokinetics of pantoprazole and its therapeutic effects: poor metabolizers of PPIs are more likely to have a better response to pantoprazole therapy and achieve better H. pylori eradication rates compared to rapid metabolizers. The determination of alleles that are associated with decreased (e.g., *2, *3 alleles) or increased (e.g., *17 allele) cytochrome 2C19 enzyme activity might be used as predictive factors for the potential of acid suppression and the success of Helicobacter pylori eradication. Overall, currently available data do not provide robust evidence, therefore, the application of genetic polymorphisms of cytochrome enzymes in clinical practice still cannot be recommended as routine practice for personalized pantoprazole prescription strategies.

Background: Oral administration of medications and current oral modified-release systems are the most preferred drug delivery routes, but they provide efficacy up to 12-24 hours per administration and are not useful when the patient has short transit time. The once-daily administered formulations are the endpoint of many types of drug development, and some innovations in capsule endoscopy (CE) can solve this problem. Objective: This review aims to reveal recent advances in drug delivery systems (DDS) for CE as an essential field of research for more precise drug targeting at the gastrointestinal (GI) tract. Methods: We performed a narrative overview of the MEDLINE database from 1991-2020 using the keywords of DDS and CE with synthesizing the findings, hand searches, and authoritative articles. Results: There are microelectromechanical systems and non-mechanical patent technologies for DDS for CE, and the implementation of wireless-capsule medical devices into the human body will provide new diagnostic and therapeutic options. Integrating biomedical CE with DDS and the cloud technology will bring remote real-time feedbackbased automated treatment or responsive medication. Conclusion: Swallowable drug delivery systems for capsule endoscopy brings an entirely new approach for diagnostic and therapeutic methods in digestive diseases.

Background: Adequate bowel cleansing is essential in achieving a good quality colonoscopy. However, one of the barriers to achieving high-quality bowel cleansing is the patient's tolerability. Different bowel preparations have been developed to improve tolerability while maintaining adequate bowel cleansing. Objectives: We aim to explore the pros and cons of commonly used bowel preparations, particularly highlighting the new ultra-low volume bowel preparation. Methods: Extensive literature search was carried out on various databases to evaluate the effectiveness and side effects of different bowel cleansing agents, including findings of recent clinical trials on ultra-low bowel preparation. Results: Polyethylene glycol (PEG) has been commonly used as a bowel prep. Due to its high volume required to ingest to achieve an adequate effect, it has been combined with various adjuncts to reduce the volume to make it more tolerable. Magnesium and phosphate-based preps can achieve low volume, but they can be associated with multiple side effects, mainly electrolyte disturbances. Ultra low volume prep (NER1006) was achieved by combing PEG with ascorbic acid, and its efficacy and side effects were demonstrated in three noninferiority studies. Conclusion: It is important to consider patient preferences, co-morbidities and tolerability, and efficacy and side effect profiles when choosing bowel prep for patients undergoing colonoscopy. New ultra-low bowel prep showed promising results in initial clinical trials, but further real-world post-marketing data will inform its value in clinical practice.

Endoscopy is in a period of continuous innovations in terms of image quality, endoscopes, post-processing software and lastly, application of Artificial Intelligence. Therapeutic boundaries have expanded, widening the grey zone between endoscopy and surgery, and increasing endoscopic approaches in clinical scenarios where, until a few years ago, surgery was the only option. New scopes and accessories have made it easier to access critical areas such as the biliary tree and the small bowel intestine. In the field of hepato-pancreato-biliary endoscopy (HPB), it is now possible to directly access the biliary ducts or cystic lesions though dedicated stents and scopes, rather than having to rely only on fluoroscopy and ultrasound, increasing the diagnostic and therapeutic options by applying a three-dimensional approach. This narrative review will give an overview of some of the most relevant emerging fields in luminal and HPB endoscopy, highlighting advantages and main limitations of the techniques, and providing considerations for future development.

Background: Hepatocellular carcinoma (HCC) is among the world’s most common cancers. For over ten years, the only medical treatment for it has been the multikinase inhibitor Sorafenib. Currently, however, other first or second-line therapeutic options have also shown efficacy against HCC, such as multikinase inhibitors (Regorafenib, Lenvatinib, and Cabozantinib), a monoclonal antibody against the vascular endothelial growth factor receptor 2 (Ramucirumab), and immune-checkpoint inhibitors (Nivolumab, Pembrolizumab, Ipilimumab). Aim: The aim of this paper is to review the metabolic pathways of drugs that have been tested for the treatment of HCC and the potential influence of liver failure over those pathways. Methods: The Food and Drug Administration (FDA)’s and European Medicines Agency (EMA)’s datasheets, results from clinical trials and observational studies have been reviewed. Results: This review summarizes the current knowledge regarding targets, metabolic pathways, drug interactions, and adverse events of medical treatments for HCC in cirrhotic patients. Conclusion: The new scenario of systemic HCC therapy includes more active drugs with different metabolic pathways and different liver adverse events. Clinical and pharmacological studies providing more data on the safety of these molecules are urgently needed.

Background: Surfactants are an important category of additives that are used widely in most of the formulations as solubilizers, stabilizers, and emulsifiers. Current drug delivery systems comprise of numerous synthetic surfactants (such as Cremophor EL, polysorbate 80, Transcutol-P), which are associated with several side effects though used in many formulations. Therefore, to attenuate the problems associated with conventional surfactants, a new generation of surface-active agents is obtained from the metabolites of fungi, yeast, and bacteria, which are termed as biosurfactants. Objectives: In this article, we critically analyze the different types of biosurfactants, their origin along with their chemical and physical properties, advantages, drawbacks, regulatory status, and detailed pharmaceutical applications. Methods: 243 papers were reviewed and included in this review. Results: Briefly, Biosurfactants are classified as glycolipids, rhamnolipids, sophorolipids, trehalolipids, surfactin, lipopeptides & lipoproteins, lichenysin, fatty acids, phospholipids, and polymeric biosurfactants. These are amphiphilic biomolecules with lipophilic and hydrophilic ends and are used as drug delivery vehicles (foaming, solubilizer, detergent, and emulsifier) in the pharmaceutical industry. Despite additives, they have some biological activity as well (anti-cancer, anti-viral, anti-microbial, P-gp inhibition, etc.). These biomolecules possess better safety profiles and are biocompatible, biodegradable, and specific at different temperatures. Conclusion: Biosurfactants exhibit good biomedicine and additive properties that can be used in developing novel drug delivery systems. However, more research should be driven due to the lack of comprehensive toxicity testing and high production cost which limits their use.

Background: Among all cancers, lung cancer has high mortality among patients in most of the countries in the world. Targeted delivery of anticancer drugs can significantly reduce the side effects and dramatically improve the effects of the treatment. Folate, a suitable ligand, can be modified to the surface of tumor-selective drug delivery systems because it can selectively bind to the folate receptor, which is highly expressed on the surface of lung tumor cells. Objective: This study aimed to construct a kind of folate-targeted topotecan liposomes for investigating their efficacy and mechanism of action in the treatment of lung cancer in preclinical models. Methods: We conjugated topotecan liposomes with folate, and the liposomes were characterized by particle size, entrapment efficiency, cytotoxicity to A549 cells and in vitro release profile. Technical evaluations were performed on lung cancer A549 cells and xenografted A549 cancer cells in female nude mice, and the pharmacokinetics of the drug were evaluated in female SD rats. Results: The folate-targeted topotecan liposomes were proven to show effectiveness in targeting lung tumors. The anti-tumor effects of these liposomes were demonstrated by the decreased tumor volume and improved therapeutic efficacy. The folate-targeted topotecan liposomes also lengthened the topotecan blood circulation time. Conclusion: The folate-targeted topotecan liposomes are effective drug delivery systems and can be easily modified with folate, enabling the targeted liposomes to deliver topotecan to lung cancer cells and kill them, which could be used as potential carriers for lung chemotherapy.