Current Drug Targets - Volume 18, Issue 11, 2017

Background: Successful delivery of therapeutic agents in the brain is very challenging, which makes treatment of various brain disorders very difficult. One of the major causes of this difficulty is the presence of physiological barriers in the brain like blood brain barrier (BBB) and blood cerebrospinal fluid (CSF) barrier. These barriers are very specific and restrict the entry of water soluble agents and ionized molecule. Objective: The current article focuses on the transcranial route, transcranial focused ultrasound (FUS), and the techniques involved in transcranial focused ultrasound (FUS) delivery and recent updates of this system. Results: The study describes that the FUS in conjunction with various other techniques opens the BBB very effectively. Conclusion: The administration of therapeutic agent using various FUS techniques opens a new perspective in treating CNS diseases.

Background: Prostate cancer (PC) is a prostate gland cells carcinoma, the foremost reason of cancer deaths in men in developed countries, representing most common malignancy in adult males. The key obstacle to achieve practicable therapeutic effect of active drugs and capable hopeful agents including proteins and peptides, and nucleic acid for prostate cancer is the scarcity of targeted drug delivery to cells of prostate cancer. As a result, need for novel systems, strategies or therapeutic approaches to enhance the assortment of active agents meant for prostate cancer becomes an important criterion. Currently cancer research focuses on improving treatment of prostate cancer using various novel drug delivery systems of chemotherapeutic agents. These novel drug delivery systems comprise nanoparticles and liposomes. Also, strategies or therapeutic approaches intended for the prostate cancer include radiation therapy for localized prostate cancer, hormonal therapy for suppressing tumor growth, and gene-and-immunologic therapy. These systems and approaches can deliver the drugs to their selected or targeted cancer cells for the drug release in cancer atmosphere of prostate thereby enhancing the effectiveness of tumor penetration. Objective: The objective was to collect and report the recent research findings to manage the PC. Present review encloses existing diverse novel drug delivery systems and approaches intended for the management of PC. Conclusion: The reported miscellaneous novel drug delivery systems along with the diverse therapies are seem to be precise, secure and relatively effective; and in consequence could lead to a new track for obliteration of prostate cancer.

Background: Recently, there are scientific attempts to discover new drugs in the biotechnology industry in order to treat various diseases including atherosclerosis. Objective: The main objective of the present review was to highlight the cellular, molecular biology and inflammatory process related to the atheromatous plaques. Methods: A thorough literature search of Pubmed, Google and Scopus databases was done. Results: Atherosclerosis is considered to be a leading cause of death throughout the world. Atherosclerosis involves oxidative damage to the cells with production of reactive oxygen species (ROS). Development of atheromatous plaques in the arterial wall is a common feature. Specific inflammatory markers pertaining to the arterial wall in atherosclerosis may be useful for both diagnosis and treatment. These include Nitric oxide (NO), cytokines, macrophage inhibiting factor (MIF), leucocytes and Pselectin. Modern therapeutic paradigms involving endothelial progenitor cells therapy, angiotensin II type-2 (AT2R) and ATP-activated purinergic receptor therapy are notable to mention. Conclusion: Future drugs may be designed aiming three signalling mechanisms of AT2R which are (a) activation of protein phosphatases resulting in protein dephosphorylation (b) activation of bradykinin/nitric oxide/cyclic guanosine 3',5'-monophosphate pathway by vasodilation and (c) stimulation of phospholipase A(2) and release of arachidonic acid. Drugs may also be designed to act on ATP-activated purinergic receptor channel type P2X7 molecules which acts on cardiovascular system.

Background: Recent reports indicate that the tumor microenvironment plays a pivotal role in cancer development and progression, leading to a paradigm shift in the way cancer is studied and targeted. In contrast to traditional approaches, where only tumor cells are targeted for the treatment, an emerging approach is to develop therapeutics which target the tumor microenvironment while complementing or enhancing current treatments. Legumain (LGMN) is a newly identified target which is highly expressed in the tumor microenvironment and in tumor cells, and holds potential both as a biomarker and as a therapeutic target. Conclusion: This review will be the first to summarize the expression of LGMN in common cancers, as well as its roles in tumorigenesis and metastasis. This review also discusses the current developments and future prospects of targeting LGMN through the development of DNA vaccines, azopeptides, small molecule inhibitors and LGMN activated prodrugs, highlighting the potential of LGMN as a target for cancer therapeutics.

Background: Global death rate due to cardiovascular diseases (CVDs) is highest as compared to other ailments. Principal risk factor associated with CVDs is hypertension. Major classes of current antihypertensive (AHT) therapies include angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARBs) and calcium channel blockers (CCBs). All these antihypertensive therapeutic drugs have low oral bioavailability and can induce upper respiratory tract abstraction, angioedema, reflex tachycardia and extreme hypotensive effect after oral administration which can cause lethal effects in patients with heart diseases. Objective: Controlled and targeted release by using antihypertensive nano-medicines can provide better solution to overcome above-mentioned side effects. Results: Scientific evolution towards the development of biopolymer based nano-carrier systems has unlocked new horizons for safe and/or edible nano drug delivery systems. In this article, we have reviewed in detail various mechanisms of AHT drugs, major draw backs associated with current therapeutic strategies, and the advantages of AHT nano-medicines over conventional drugs. Furthermore, recent reports of bio-based nano/micro -carrier systems with different AHT drugs have been analyzed with their key features. In depth review has been presented for chitosan as a potential carrier of AHT drugs due to its distinctive properties comprising muco-adhesive attribute, permeation enhancement as well as its biocompatible and biodegradable nature. Conclusion: Chitosan based novel AHT nano-ceuticals can improve oral bioavailability, reduce hydrophobicity and increase the plasma half-life of AHT drugs by their sustained release in lower part of the GIT.

Bone is one of the most common and most dangerous sites for metastatic growth across cancer types, and bone metastasis remains incurable. Unfortunately, the processes by which cancers preferentially metastasize to bone are still not well understood. In this review, we summarize the morphological features, physical properties, and cell signaling events that make bone a unique site for metastasis and bone remodeling. The signaling crosstalk between the tumor cells and bone cells begins a vicious cycle – a self-sustaining feedback loop between the tumor cells and the bone microenvironment composed of osteoclasts, osteoblasts, other bone marrow cells, bone matrix, and vasculature to support both tumor growth and bone destruction. Through this crosstalk, bone provides a fertile microenvironment that can harbor dormant tumor cells, sometimes for long periods, and support their growth by releasing cytokines as the bone matrix is destroyed, similar to providing nutrients for a seed to germinate in soil. However, few models exist to study the late stages of bone colonization by metastatic tumor cells. We describe some of the current methodologies used to study bone metastasis, highlighting the limitations of these methods and alternative future strategies to be used to study bone metastasis. While in vivo animal and patient studies may provide the gold standard for studying metastasis, ex vivo models can be used as an alternative to enable more controlled experiments designed to study the late stages of bone metastasis.

Background: The natural polysaccharides contain plant polysaccharides, animal polysaccharides and microbial polysaccharides. They are a kind of biological macromolecules with immune regulation, anti-tumor, anti-radiation, anti-inflammation, anti-fatigue and anti-aging effects. Objective: These effects are related to their antioxidant properties. Results: The action mechanisms of antioxidation and scavenging free radicals for natural polysaccharides were reviewed. The recent research progresses and our work on antioxidant properties of polysaccharides and their derivatives were summarized. At last, the existing problems of antioxidant polysaccharides were analyzed, and the development prospects were also presented. Conclusion: It is important to study the antioxidant activities of polysaccharides and their derivatives for the development of natural antioxidants.

Background: The renin angiotensin system (RAS) plays an important role in inflammation and fibrosis. The classical axis of the RAS, formed by angiotensin converting en-zyme (ACE), angiotensin II (Ang II) and angiotensin receptor type 1 (AT1), activates several cell functions and molecular signaling pathways related to tissue injury, inflammation and fibrosis. In sharp contrast, the RAS axis composed by angiotensin converting enzyme 2 (ACE2), angiotensin-(1-7) and Mas receptor exerts opposite effects in relation to inflammatory response and tissue fibrosis. Objective: In this review, we have the aim to summarize recent findings on the anti-inflammatory and anti-fibrogenic role of ACE2/Ang-(1-7)/Mas axis in the context of basic research, experimental human dis-eases and clinical studies. Results: Several studies showed that ACE2/Angiotensin-(1-7)/Mas axis reduces cytokine release and inhibits signaling pathways of tissue fibrosis in experimental models of human diseases including atherosclerosis, cerebral ischemia, obesity, chronic kidney disease, liver diseases and asthma. On the other hand, very few data was provided by clinical studies. Conclusion: Experimental studies clearly support the anti-inflammatory and anti-fibrotic effects of ACE2/ Ang-(1-7)/Mas axis. Clinical studies, especially phase III and IV trials, will be necessary to establish the therapeutic role of ACE2/Ang-(1-7)/Mas axis in controlling inflammation in different human diseases.