Current Medicinal Chemistry - Volume 27, Issue 10, 2020

Medical devices are important diagnosis and therapy tools for several diseases which include a wide range of products. Technological advances in this area have been proposed to reduce adverse complication incidences. New technologies and manufacturing processes, as well as the development of new materials or medical devices with modified surface and the use of biodegradable polymeric devices such as a substrate for cell culture in the field of tissue engineering, have attracted considerable attention in recent years by the scientific community intended to produce medical devices with superior properties and morphology. This review article focused on implantable devices, addresses the major advances in the biomedical field related to the devices manufacture processes such as 3D printing and hot melting extrusion, and the use of polymer matrices composed of copolymers, blends, nanocomposites or grafted with antiproliferative drugs for manufacturing and/or coating the devices surface.

Radioembolization (RE) is a valuable treatment for liver cancer. It consists of administering radioactive microspheres by an intra-arterially placed catheter with the aim of lodging these microspheres, which are driven by the bloodstream, in the tumoral bed. Even though it is a safe treatment, some radiation-induced complications may arise. In trying to detect or solve the possible incidences that cause nontarget irradiation, simulating the particle- hemodynamics in hepatic arteries during RE by computational fluid dynamics (CFD) tools has become a valuable approach. This paper reviews the parameters that influence the outcome of RE and that have been studied via numerical simulations. In this numerical approach, the outcome of RE is regarded as successful if particles reach the artery branches that feed tumor-bearing liver segments. Up to 10 parameters have been reviewed. The variation of each parameter actually alters the hemodynamic pattern in the vicinities of the catheter tip and locally alters the incorporation of the particles into the bloodstream. Therefore, in general, the local influences of these parameters should result in global differences in terms of particle distribution in the hepatic artery branches. However, it has been observed that under some (qualitatively described) appropriate conditions where particles align with blood streamlines, the local influence resulting from a variation of a given parameter vanishes and no global differences are observed. Furthermore, the increasing number of CFD studies on RE suggests that numerical simulations have become an invaluable research tool in the study of RE.

Polymeric materials, due to their excellent physicochemical properties and versatility found applicability in multiples areas, including biomaterials used in tissue regeneration, prosthetics (hip, artificial valves), medical devices, controlled drug delivery systems, etc. Medical devices and their applications are very important in modern medicine and the need to develop new materials with improved properties or to improve the existent materials is increasing every day. Numerous reasearches are activated in this domain in order to obtain materials/surfaces that does not have drawbacks such as structural failure, calcifications, infections or thrombosis. One of the most used material is poly(vinylchloride) (PVC) due to its unique properties, availability and low cost. The most common method used for obtaining tubular devices that meet the requirements of medical use is the surface modification of polymers without changing their physical and mechanical properties, in bulk. PVC is a hydrophobic polymer and therefore many research studies were conducted in order to increase the hydrophilicity of the surface by chemical modification in order to improve biocompatibility, to enhance wettability, reduce friction or to make lubricious or antimicrobial coatings. Surface modification of PVC can be achieved by several strategies, in only one step or, in some cases, in two or more steps by applying several techniques consecutively to obtain the desired modification / performances. The most common processes used for modifying the surface of PVC devices are: plasma treatment, corona discharge, chemical grafting, electric discharge, vapour deposition of metals, flame treatment, direct chemical modification (oxidation, hydrolysis, etc.) or even some physical modification of the roughness of the surface.

Treatment of cardiovascular disease has achieved great success using artificial implants, particularly synthetic-polymer made grafts. However, thrombus formation and restenosis are the current clinical problems need to be conquered. New biomaterials, modifying the surface of synthetic vascular grafts, have been created to improve long-term patency for the better hemocompatibility. The vascular biomaterials can be fabricated from synthetic or natural polymers for vascular tissue engineering. Stem cells can be seeded by different techniques into tissue-engineered vascular grafts in vitro and implanted in vivo to repair the vascular tissues. To overcome the thrombogenesis and promote the endothelialization effect, vascular biomaterials employing nanotopography are more bio-mimic to the native tissue made and have been engineered by various approaches such as prepared as a simple surface coating on the vascular biomaterials. It has now become an important and interesting field to find novel approaches to better endothelization of vascular biomaterials. In this article, we focus to review the techniques with better potential improving endothelization and summarize for vascular biomaterial application. This review article will enable the development of biomaterials with a high degree of originality, innovative research on novel techniques for surface fabrication for vascular biomaterials application.

Matrix Gla protein (MGP) is a vitamin K-dependent protein, which is synthesized in bone and many other mesenchymal cells, which is also highly expressed by vascular smooth muscle cells (VSMCs) and chondrocytes. Numerous studies have confirmed that MGP acts as a calcification-inhibitor although the mechanism of action is still not fully understood. The modulation of tissue calcification by MGP is potentially regulated in several ways including direct inhibition of calcium-phosphate precipitation, the formation of matrix vesicles (MVs), the formation of apoptotic bodies (ABs), and trans-differentiation of VSMCs. MGP occurs as four species, i.e. fully carboxylated (cMGP), under-carboxylated, i.e. poorly carboxylated (ucMGP), phosphorylated (pMGP), and non-phosphorylated (desphospho, dpMGP). ELISA methods are currently available that can detect the different species of MGP. The expression of the MGP gene can be regulated via various mechanisms that have the potential to become genomic biomarkers for the prediction of vascular calcification (VC) progression. VC is an established risk factor for cardiovascular disease and is particularly prevalent in those with chronic kidney disease (CKD). The specific action of MGP is not yet clearly understood but could be involved with the functional inhibition of BMP-2 and BMP-4, by blocking calcium crystal deposition and shielding the nidus from calcification.

Background: This paper provides a critical review of biopolymer-based substrates, especially the cellulose derivatives, for their application in buccal drug delivery. Drug delivery to the buccal mucous has the benefits of immobile muscle, abundant vascularization and rapid recovery, but not all the drugs can be administered through the buccal mucosa (e.g., macromolecular drugs), due to the low bioavailability caused by their large molecular size. This shortfall inspired the rapid development of drug-compounding technologies and the corresponding usage of biopolymer substrates. Methods: Cellulose derivatives have been extensively developed for drug manufacturing to facilitate its delivery. We engaged in structured research of cellulose-based drug compounding technologies. We summarized the characteristic cellulose derivatives which have been used as the biocompatible substrates in buccal delivery systems. The discussion of potential use of the rapidly-developed nanocellulose (NC) is also notable in this paper. Results: Seventy-eight papers were referenced in this perspective paper with the majority (sixty-five) published later than 2010. Forty-seven papers defined the buccal drug delivery systems and their substrates. Fifteen papers outlined the properties and applications of cellulose derivatives. Nanocellulose was introduced as a leading edge of nanomaterial with sixteen papers highlighted its adaptability in drug compounding for buccal delivery. Conclusion: The findings of this perspective paper proposed the potential use of cellulose derivatives, the typical kind of biopolymers, in the buccal drug delivery system for promoting the bioavailability of macromolecular drugs. Nanocellulose (NC) in particular was proposed as an innovative bio-binder/carrier for the controlled-release of drugs in buccal system.

Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) play crucial and often opposing regulatory roles in health and in pathological conditions. n-3 and n-6 PUFA undergo biotransformation to parallel series of lipid mediators that are potent modulators of many cellular processes. A wide range of biological actions have been attributed to lipid mediators derived from n-6 PUFA, and these mediators have served as lead compounds in the development of numerous clinically approved drugs, including latanoprost (Xalatan: Pfizer), which is listed on the WHO Model List of Essential Medicines. n-3 PUFA-derived mediators have received less attention, in part because early studies suggested that n-3 PUFA act simply as competitive substrates for biotransformation enzymes and decrease the formation of n-6 PUFA-derived lipid mediators. However, more recent studies suggest that n-3 PUFA-derived mediators are biologically important in their own right. It is now emerging that many n-3 PUFA-derived lipid mediators have potent and diverse activities that are distinct from their n-6 counterparts. These findings provide new opportunities for drug discovery. Herein, we review the biosynthesis of n-3 PUFA-derived lipid mediators and highlight their biological actions that may be exploited for drug development. Lastly, we provide examples of medicinal chemistry research that has utilized n-3 PUFA-derived lipid mediators as novel lead compounds in drug design.

Background: The pathophysiology and neurochemical mechanisms of essential tremor (ET) are not fully understood, because only a few post-mortem studies have been reported, and there is a lack of good experimental model for this disease. Objective: The main aim of this review is to update data regarding the neurochemical features of ET. Alterations of certain catecholamine systems, the dopaminergic, serotonergic, GABAergic, noradrenergic, and adrenergic systems have been described, and are the object of this revision. Methods: For this purpose, we performed a literature review on alterations of the neurotransmitter or neuromodulator systems (catecholamines, gammaaminobutyric acid or GABA, excitatory amino acids, adenosine, T-type calcium channels) in ET patients (both post-mortem or in vivo) or in experimental models resembling ET. Results and Conclusion: The most consistent data regarding neurochemistry of ET are related with the GABAergic and glutamatergic systems, with a lesser contribution of adenosine and dopaminergic and adrenergic systems, while there is not enough evidence of a definite role of other neurotransmitter systems in ET. The improvement of harmaline-induced tremor in rodent models achieved with T-type calcium channel antagonists, cannabinoid 1 receptor, sphingosine-1-phosphate receptor agonists, and gap-junction blockers, suggests a potential role of these structures in the pathogenesis of ET.