Current Medicinal Chemistry (v.24, #22)
Cyclodextrins Based Electrochemical Sensors for Biomedical and Pharmaceutical Analysis by Joanna Lenik (2359-2391).
Electrochemical sensors are very convenient devices, as they may be used in a lot of fields starting from the food industry to environmental monitoring and medical diagnostics. They offer the values of simple design, reversible and reproducible measurements, as well as ensuring precise and accurate analytical information. Compared with other methods, electrochemical sensors are relatively simple as well as having low costs, which has led to intensive development, especially in the field of medicine and pharmaceuticals within the last decade. Recently, the number of publications covering the determination of aminoacids, dopamine, cholesterol, uric acid, biomarkers, vitamins and other pharmaceutical and biological compounds has significantly increased. Many possible types of such sensors and biosensors have been proposed: owing to the kind of the detection-potentiometric voltametric, amperometry, and the materials that can be used for, e.g. designing molecular architecture of the electrode/solution interface, carbon paste, carbon nanotubes, glass carbon, graphite, graphene, PVC, conductive polymers and/or nanoparticles. The active compounds which provide the complex formation with analyte (in the case of non-current techniques) or activate biomolecules electrochemically by particle recognition and selective preconcentration of analyte on the electrode surface (in the case of current techniques) are the most recently used cyclodextrins. These macrocyclic compounds have the ability to interact with a large diversity of guest particles to form complexes of the type of guest host, for example, with particles from drugs, biomolecules, through their hydrophilic outer surface and lipophilic inner cavities. Cyclodextrins have been the subject of frequent electrochemical studies that focused mostly on both their interactions in a solid state and in solution. The process of preparing of CDs modified electrodes would, consequently, open new avenues for new electrochemical sensors and, therefore, widen their use in biomedical and drug analysis. <P></P> This review presents information on manufacturing techniques and performances of these sensors and biosensors. The opportunities for these sensors to carry out biomedical and pharmaceutical researches are demonstrated.
Targeting Malassezia species for Novel Synthetic and Natural Antidandruff Agents by Letizia Angiolella, Simone Carradori, Cristina Maccallini, Gustavo Giusiano, Claudiu T. Supuran (2392-2412).
<i>Malassezia</i> spp. are lipophilic yeasts not only present in the normal skin microflora, but also responsible of skin-related diseases (pityriasis versicolor, seborrheic/atopic dermatitis and dandruff) as well as systemic fungal infections in humans and animals. Their treatment and eradication are mainly based on old azole drugs, which are characterized by poor compliance, unpredictable clinical efficacy, emerging resistance and several side effects. These drawbacks have prompted the research toward novel synthetic and natural derivatives/ nanomaterials targeting other pivotal enzymes/pathways such as carbonic anhydrase (MgCA) and lipases, alone or in combination, in order to improve the eradication rate of this fungus. This review accomplished an update on this important topic dealing with the latest discoveries of synthetic scaffolds and natural products for the treatment of <i>Malassezia</i>spp.-related diseases, thus suggesting new opportunities to design innovative and alternative anti-dandruff drugs.
Microneedle Patches as Drug and Vaccine Delivery Platform by Junwei Li, Mingtao Zeng, Hu Shan, Chunyi Tong (2413-2422).
Background: Transcutaneous delivery is the ideal method for delivering therapeutic reagents or vaccines into skin. With their promise of self-administration, cost-effective and high efficiency, microneedle patches have been studied intensively as therapeutic and vaccination delivery platform that replaces injection by syringe. This review aims to summarize the recent advancements of microneedle patches in application for drugs and vaccine delivery. <P></P> Methods: We reviewed the most of recently published papers on microneedle patches, summarized their evolution, classification, state-of the-art capabilities and discussed promising application in drugs and vaccine delivery. <P></P> Results: With the rapid development of nanotechnology, microneedle patches have been improved by switching from undissolving to dissolving microneedles, and their safety has also improved dramatically. As a drug delivery tool, microneedle patches can deliver bioactive molecular of different physical size. Additionally, microneedle patches can be coated or encapsulate with DNA vaccine, subunit antigen, inactivated or live virus vaccine. Combining clinical results with the results of patient interview, microneedle patches are found to be feasible and are predicated to soon be acceptable for the medical service. <P></P> Conclusion: In this review, we summarized the evolution, current and future application of microneedle patches as delivery vehicle for drugs and vaccines. Compared with traditional delivery tools, microneedle patches have many advantages, such as providing pain-free, non-invasive, convenient route for reagent administration and delivery, with no cold chain required for storage and transportation as well as decreasing sharp medical waste, needle-caused injury and transmission of blood-borne infectious disease in rural area. However, even though there are dramatic progress in preclinical investigation of microneedle patches, further testing will be required for clinical application. Further research should be implemented in multiple fields, such as vaccinology, immunology, and materials science, to improve this delivery platform. Because of their advantages in dose sparing, safety and treatment compliance, microneedle patches are expected to be widely applied in clinical treatment and vaccine administration in near future.
Polymeric Biomaterial and Lipid Based Nanoparticles for Oral Drug Delivery by Fahima Dilnawaz (2423-2438).
Background: Oral drug delivery is widespread owing to its non-invasive nature which complements high patient compliance. However, the drug administration via oral route is quite challenging due to the presence of the biochemical barriers which hinders the uptake as well as access to blood stream. Apart from that, stability, poor solubility and bioavailability of administered drug via the gastrointestinal (GI) tract are also exigent. Till now various oral formulations were developed which releases the drug in a timely manner but lacks appropriate therapeutic concentration. <P></P> Objective: Recently nanoparticles based drug delivery system has emerged as prominent strategy for optimizing the oral drug delivery and maximizing the treatment efficiency. Besides, different strategic polymeric nanoparticles are engineered for interaction both at extracellular and intracellular levels with gastrointestinal mucosa. <P></P> Methods: The review article focuses on the polymeric and lipid based various nanocarriers that have been widely studied for the enhanced oral drug delivery of different therapeutic molecules and addresses recent progress of biocompatible and biodegradable polymeric nanoparticles approach for its improvement. <P></P> Conclusion: The progress of numerous oral nanoparticulate drug delivery vehicles will be immensely helpful to improve therapeutic efficacy with reduced adverse side effects. Unlike other forms of administration, it will have better patient compliance and soothing effect. The oral drug delivery will certainly play a pivotal role soon in expanding the clinical repertoire and applications.
Exploitation of Novel Molecular Targets to Treat Idiopathic Pulmonary Fibrosis: A Drug Discovery Perspective by Bhuvaneshwar Vaidya, Ruaab Patel, Aaron Muth, Vivek Gupta (2439-2458).
Background: Idiopathic pulmonary fibrosis (IPF) is the most common fibrosing lung disease and is caused by excessive lung scarring. IPF-associated severe mortality can be attributed to late diagnosis due to its generic symptoms, and more importantly due to the lack of effective therapies available. Despite extensive research in the past decades, lung transplant still remains the most effective treatment for IPF. Though two drugs recently approved by FDA, Pirfenidone and Nintedanib, have shown an ability to reduce the progression of disease. However, they have shown minimal survival benefits to patients. <P></P> Methods: IPF is a multifaceted disorder with poorly understood pathophysiology. We believe that there are better therapeutic targets veiled in IPF pathophysiology, exploitation of which may improve current therapeutic approaches to the disease. We have performed an extensive literature search using several bibliographic databases for peer reviewed articles discussing molecular targets/pathways involved in the pathogenesis of the disease. Furthermore, studies involving exploitation of these therapeutic targets and potential therapeutic agents were identified. <P></P> Results: Recently, new and promising targets have been revealed from GWA studies and genetic microarrays of IPF patients. In this review, we discuss the efficacy and feasibility of several novel molecular targets including Semaphorin (SEMA) 7A, connective tissue growth factor, integrin αvβ6, caveolin-1, let 7-d, calcium activated potassium channel KCa3.1, matrix metalloproteinase-19, lysocardiolipin acetyltransferase, dimethylarginine dimethylaminohydrolase, and transglutaminase 2. These targets have all shown the potential to modulate IPF pathophysiology, thereby inhibiting disease progression. <P></P> Conclusion: Information gained from this review will be valuable to this field, enabling the design and development of novel therapeutics for IPF.