Current Medicinal Chemistry - Volume 27, Issue 4, 2020

Positron Emission Tomography (PET) and Single Photon Emission Computerized Tomography (SPECT) are ultra-sensitive, fully translational and minimally invasive nuclear imaging techniques capable of tracing the spatiotemporal distribution of positron (PET) or gamma (SPECT) emitter-labeled molecules after administration into a living organism. Besides their impact in the clinical diagnostic, PET and SPECT are playing an increasing role in the process of drug development, both during the evaluation of the pharmacokinetic properties of new chemical entities as well as in the proof of concept, proof of mechanism and proof of efficacy studies. However, they have been scarcely applied in the context of ophthalmic drugs. In this paper, the basics of nuclear imaging and radiochemistry are briefly discussed, and the few examples of the use of these imaging modalities in ophthalmic drug development reported in the literature are presented and discussed. Finally, in a purely theoretical exercise, some labeling strategies that could be applied to the preparation of selected ophthalmic drugs are proposed and potential applications of nuclear imaging in ophthalmology are projected.

Background: Numerous studies have analysed the effect of using different Contact Lenses (CLs) or care solutions, and suffering discomfort or diseases associated with CL wear on the inflammatory mediator release into the tears. Objective: To summarize the published data on tear inflammatory molecules related to CL use. Methods: A PubMed-NCBI search has been conducted and those publications which carried out original investigations including the analysis of tear inflammatory mediators in CL wearers were selected. Results: Forty-three articles, from 1990 to 2019, have been included. Wearing hydrogel CLs, rigid gas permeable CLs, and special designs for irregular corneas in keratoconus patients (CLs with keratoconic design, hybrid CLs, piggyback fit, and scleral CLs) have been reported to alter the concentration of several molecules in tears. Moreover, there seems to be an effect of the wearing time and schedule, CL materials and designs, and care solutions used. Regarding CL discomfort, its relation with inflammatory mediators is not clear. However, some diseases associated to CL wear, such as giant papillary conjunctivitis, CL induced acute red eye, CL induced peripheral ulcer, and acanthamoeba keratitis have been related to the release of certain inflammatory mediators, which may serve as potential biomarkers. Conclusion: There is evidence suggesting that different aspects of CL wear alter the inflammatory mediator profile in tears, which may indicate an inflammatory state of the lacrimal functional unit. However, more studies need to be carried out to better understand how this inflammatory process works and its repercussion on the different aspects of CL wear.

The current review is focussing different factors that contribute and directly correlate to the onset and progression of Age-related Macular Degeneration (AMD). In particular, the susceptibility to AMD due to genetic and non-genetic factors and the establishment of risk scores, based on the analysis of different genes to measure the risk of developing the disease. A correlation with the actual therapeutic landscape to treat AMD patients from the point of view of pharmacokinetics and pharmacogenetics is also exposed. Treatments commonly used, as well as different regimes of administration, will be especially important in trying to classify individuals as “responders” and “non-responders”. Analysis of different genes correlated with drug response and also the emerging field of microRNAs (miRNAs) as possible biomarkers for early AMD detection and response will be also reviewed. This article aims to provide the reader a review of different publications correlated with AMD from the molecular and kinetic point of view as well as its commonly used treatments, major pitfalls and future directions that, to our knowledge, could be interesting to assess and follow in order to develop a personalized medicine model for AMD.

The administration of drugs to treat ocular disorders still remains a technological challenge in this XXI century. Although there is an important arsenal of active molecules useful to treat ocular diseases, ranging from classical compounds to biotechnological products, currenty, no ideal delivery system is able to profit all their therapeutic potential. Among the Intraocular Drug Delivery Systems (IODDS) proposed to overcome some of the most important limitations, microsystems and nanosystems have raised high attention. While microsystems are able to offer long-term release after intravitreal injection, nanosystems can protect the active compound from external environment (reducing their clearance) and direct it to its target tissues. In recent years, some researchers have explored the possibility of combining micro and nanosystems in “Nanoparticle-in-Microparticle (NiMs)” systems or “trojan systems”. This excellent idea is not exempt of technological problems, remains partially unsolved, especially in the case of IODDS. The objective of the present review is to show the state of art concerning the design, preparation and characterization of trojan microparticles for drug delivery and to remark their potential and limitations as IODDS, one of the most important challenges faced by pharmaceutical technology at the moment.

Age-related macular degeneration is an acquired degenerative disease that is responsible for severe loss of vision in elderly people. There are two types: dry age-related macular degeneration and wet age-related macular degeneration. Its treatment has been improved and tries to be tailored in the future. The aim of this review is to summarize the pharmacological advances in the treatment of age-related macular degeneration. Regarding dry AMD, there is no effective treatment to reduce its progression. However, some molecules such as lampalizumab and eculizumab were under investigation, although they have shown low efficacy. Herein, in an attempt to prevent dry AMD progression, the most important studies suggested increasing the antioxidants intake and quitting the smoke habit. On the other hand, wet AMD has more developed treatment. Nowadays, the gold standard treatment is anti-VEGF injections. However, more effective molecules are currently under investigation. There are different molecules under research for dry AMD and wet AMD. This fact could help us treat our patients with more effective and lasting drugs but more clinical trials and safety studies are required in order to achieve an optimal treatment.

Glioma, especially its most malignant type, Glioblastoma (GBM), is the most common and the most aggressive malignant tumour in the central nervous system. Currently, we have no specific therapies that can significantly improve its dismal prognosis. Recent studies have reported promising in vitro experimental results of several novel glioma-targeting drugs; these studies are encouraging to both researchers and patients. However, clinical trials have revealed that novel compounds that focus on a single, clear glioma genetic alteration may not achieve a satisfactory outcome or have side effects that are unbearable. Based on this consensus, phytochemicals that exhibit multiple bioactivities have recently attracted much attention. Traditional Chinese medicine and traditional Indian medicine (Ayurveda) have shown that phytocompounds inhibit glioma angiogenesis, cancer stem cells and tumour proliferation; these results suggest a novel drug therapeutic strategy. However, single phytocompounds or their direct usage may not reverse comprehensive malignancy due to poor histological penetrability or relatively unsatisfactory in vivo efficiency. Recent research that has employed temozolomide combination treatment and Nanoparticles (NPs) with phytocompounds has revealed a powerful dual-target therapy and a high blood-brain barrier penetrability, which is accompanied by low side effects and strong specific targeting. This review is focused on major phytocompounds that have contributed to glioma-targeting treatment in recent years and their role in drug resistance inhibition, as well as novel drug delivery systems for clinical strategies. Lastly, we summarize a possible research strategy for the future.

Background: Tuberculosis (TB) has been present in the history of human civilization since time immemorial and has caused more deaths than any other infectious disease. It is still considered one of the ten most common epidemiologic causes of death in the world. As a transmissible disease, it is initiated by rod-shaped (bacillus) mycobacteria. The management of tuberculosis became possible owing to several discoveries beginning in 1882 with the isolation of the TB bacillus by Robert Koch. The diagnosis of TB was enabled by finding a staining method for TB bacteria identification (1883). It was soon realized that a large-scale policy for the treatment and prevention of tuberculosis was necessary, which resulted in the foundation of International Union against Tuberculosis and Lung Diseases (1902). An antituberculosis vaccine was developed in 1921 and has been in therapeutic use since then. TB treatment regimens have changed over the decades and the latest recommendations are known as Directly Observed Treatment Short-course (DOTS, WHO 1993). Methods: A search of bibliographic databases was performed for peer-reviewed research literature. A focused review question and inclusion criteria were applied. Standard tools were used to assess the quality of retrieved papers. Results: A total of 112 papers were included comprising original publications and reviews. The paper overviews anti-TB drugs according to their mechanism of action. The chemical structure, metabolism and unwanted effects of such drugs have been discussed. The most recent treatment regimens and new drugs, including those in clinical trials, are also presented. Conclusion: Despite a 22% decrease in the tuberculosis fatality rate observed between 2000 and 2015, the disease remains one of the ten prime causes of death worldwide. Increasing bacterial resistance and expensive, prolonged therapies are the main reasons for efforts to find effective drugs or antituberculosis regimens, especially to cure multidrug-resistant tuberculosis.