Recent Advances in Understanding the Pathogenesis of Cardiovascular Diseases and Development of Treatment Modalities

2019 ◽  
Vol 19 (1) ◽  
pp. 19-32 ◽  
Author(s):  
Rahul Mittal ◽  
Vasanti M. Jhaveri ◽  
Sae-In Samantha Kay ◽  
Aubrey Greer ◽  
Kyle J. Sutherland ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cardiovascular Diseases ◽  
Molecular Mechanisms ◽  
Plaque Rupture ◽  
Treatment Modalities ◽  
Plaque Progression ◽  
First Line ◽  
Optimal Drug ◽  
Novel Drug ◽  
Underlying Pathology

Cardiovascular Diseases (CVDs) are a leading cause of morbidity and mortality worldwide. The underlying pathology for cardiovascular disease is largely atherosclerotic in nature and the steps include fatty streak formation, plaque progression and plaque rupture. While there is optimal drug therapy available for patients with CVD, there are also underlying drug delivery obstacles that must be addressed. Challenges in drug delivery warrant further studies for the development of novel and more efficacious medical therapies. An extensive understanding of the molecular mechanisms of disease in combination with current challenges in drug delivery serves as a platform for the development of novel drug therapeutic targets for CVD. The objective of this article is to review the pathogenesis of atherosclerosis, first-line medical treatment for CVD, and key obstacles in an efficient drug delivery.

scholarly journals Multifunctional lipidic nanocarriers for effective therapy of glioblastoma: recent advances in stimuli-responsive, receptor and subcellular targeted approaches

2021 ◽  
Author(s):  
Manasa Manjunath Hegde ◽  
Suma Prabhu ◽  
Srinivas Mutalik ◽  
Abhishek Chatterjee ◽  
Jayant S. Goda ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Current Treatment ◽  
Treatment Modalities ◽  
Cancer Type ◽  
Stimuli Responsive ◽  
Term Survival ◽  
Oncology Research ◽  
Optimal Drug ◽  
Lipid Nanocarriers ◽  
Surface Modified

Abstract Background Glioblastoma, or glioblastoma multiforme (GBM), remains a fatal cancer type despite the remarkable progress in understanding the genesis and propagation of the tumor. Current treatment modalities, comprising mainly of surgery followed by adjuvant chemoradiation, are insufficient for improving patients' survival owing to existing hurdles, including the blood–brain barrier (BBB). In contemporary practice, the prospect of long-term survival or cure continues to be a challenge for patients suffering from GBM. This review provides an insight into the drug delivery strategies and the significant efforts made in lipid-based nanoplatform research to circumvent the challenges in optimal drug delivery in GBM. Area covered Owing to the unique properties of lipid-based nanoplatforms and advancements in clinical translation, this article describes the application of various stimuli-responsive lipid nanocarriers and tumor subcellular organelle-targeted therapy to give an idea about the strategies that can be applied to enhance site-specific drug delivery for GBM. Furthermore, active targeting of drugs via surface-modified lipid-based nanostructures and recent findings in alternative therapeutic platforms such as gene therapy, immunotherapy, and multimodal therapy have also been overviewed. Expert opinion Lipid-based nanoparticles stand out among the other nanocarriers explored for GBM drug delivery, as they support both passive and active drug targeting by crossing/bypassing the BBB at the same time minimizing toxicity and projects better pharmacological parameters. Although these nanocarriers could be a plausible choice for treating GBM, in-depth research is essential to advance neuro-oncology research and enhance outcomes in patients with brain tumors.

Nanotheranostics in Evidence Based Personalized Medicine

2014 ◽  
Vol 15 (10) ◽  
pp. 915-930 ◽  
Author(s):  
Sushil Sharma
Keyword(s):  
Drug Delivery ◽  
Drug Discovery ◽  
Cardiovascular Diseases ◽  
Personalized Medicine ◽  
Neurodegenerative Diseases ◽  
Evidence Based ◽  
Significant Information ◽  
Clinically Significant ◽  
The Right ◽  
Novel Drug

Efficient drug delivery systems are exceedingly important for novel drug discovery. The evidence-based personalized medicine (EBPM) promises to deliver the right drug at the right time to a right patient as it covers clinicallysignificant genetic predisposition and chronopharmacological aspects of nanotheranostics. Recently nanotechnology has provided clinically-significant information at the cellular, molecular, and genetic level to facilitate evidence-based personalized treatment. Particularly drug encapsulation in pegylated liposomes has improved pharmacodynamics of cancer, cardiovascular diseases, and neurodegenerative diseases. Long-circulating liposomes and block copolymers concentrate slowly via enhanced permeability and retention (EPR) effect in the solid tumors and are highly significant for the drug delivery in cancer chemotherapeutics. Selective targeting of siRNA and oligonucleotides to tumor cells with a potential to inhibit multi-drug resistant (MDR) malignancies has also shown promise. In addition, implantable drug delivery devices have improved the treatment of several chronic diseases. Recently, microRNA, metallothioneins (MTs), α-synuclein index, and Charnoly body (CB) have emerged as novel drug discovery biomarkers. Hence CB antagonists-loaded ROSscavenging targeted nanoparticles (NPs) may be developed for the treatment of neurodegenerative and cardiovascular diseases. Nonspecific induction of CBs in the hyper-proliferative cells may cause alopecia, gastrointestinal tract (GIT) symptoms, myelosuppression, neurotoxicity, and infertility. Therefore selective CB agonists may be developed to augment cancer stem cell specific CB formation to eradicate MDR malignancies with minimum or no adverse effects. This review highlights recent advances on safe, economical, and effective treatment of neurodegenerative diseases, cardiovascular diseases, and cancer by adopting emerging nanotheranostic strategies to accomplish EBPM.

Role of MCP-1 in cardiovascular disease: molecular mechanisms and clinical implications

2009 ◽  
Vol 117 (3) ◽  
pp. 95-109 ◽  
Author(s):  
Jianli Niu ◽  
Pappachan E. Kolattukudy
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Molecular Mechanisms ◽  
Zinc Finger Protein ◽  
Plaque Rupture ◽  
Inflammatory Diseases ◽  
Critical Role ◽  
Protective Effects ◽  
Ischaemia Reperfusion Injury

Many of the major diseases, including cardiovascular disease, are widely recognized as inflammatory diseases. MCP-1 (monocyte chemotactic protein-1) plays a critical role in the development of cardiovascular diseases. MCP-1, by its chemotactic activity, causes diapedesis of monocytes from the lumen to the subendothelial space where they become foam cells, initiating fatty streak formation that leads to atherosclerotic plaque formation. Inflammatory macrophages probably play a role in plaque rupture and the resulting ischaemic episode as well as restenosis after angioplasty. There is strong evidence that MCP-1 plays a major role in myocarditis, ischaemia/reperfusion injury in the heart and in transplant rejection. MCP-1 also plays a role in cardiac repair and manifests protective effects under certain conditions. Such protective effects may be due to the induction of protective ER (endoplasmic reticulum) stress chaperones by MCP-1. Under sustained ER stress caused by chronic exposure to MCP-1, the protection would break down resulting in the development of heart failure. MCP-1 is also involved in ischaemic angiogenesis. The recent advances in our understanding of the molecular mechanisms that might be involved in the roles that MCP-1 plays in cardiovascular disease are reviewed. The gene expression changes induced by the signalling events triggered by MCP-1 binding to its receptor include the induction of a novel zinc-finger protein called MCPIP (MCP-1-induced protein), which plays critical roles in the development of the pathophysiology caused by MCP-1 production. The role of the MCP-1/CCR2 (CC chemokine receptor 2) system in diabetes, which is a major risk factor for cardiovascular diseases, is also reviewed briefly. MCP-1/CCR2- and/or MCPIP-targeted therapeutic approaches to intervene in inflammatory diseases, including cardiovascular diseases, may be feasible.

scholarly journals Recent Advances in Tannic Acid (Gallotannin) Anticancer Activities and Drug Delivery Systems for Efficacy Improvement; A Comprehensive Review

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1486 ◽  
Author(s):  
Rana A. Youness ◽  
Rabab Kamel ◽  
Nermeen A. Elkasabgy ◽  
Ping Shao ◽  
Mohamed A. Farag
Keyword(s):  
Drug Delivery ◽  
Tannic Acid ◽  
Drug Delivery Systems ◽  
Molecular Mechanisms ◽  
Delivery Systems ◽  
Clinical Applications ◽  
Lipid Solubility ◽  
Anticancer Activities ◽  
Cancer Management ◽  
Novel Drug

Tannic acid is a chief gallo-tannin belonging to the hydrolysable tannins extracted from gall nuts and other plant sources. A myriad of pharmaceutical and biological applications in the medical field has been well recognized to tannic acid. Among these effects, potential anticancer activities against several solid malignancies such as liver, breast, lung, pancreatic, colorectal and ovarian cancers have been reported. Tannic acid was found to play a maestro-role in tuning several oncological signaling pathways including JAK/STAT, RAS/RAF/mTOR, TGF-β1/TGF-β1R axis, VEGF/VEGFR and CXCL12/CXCR4 axes. The combinational beneficial effects of tannic acid with other conventional chemotherapeutic drugs have been clearly demonstrated in literature such as a synergistic anticancer effect and enhancement of the chemo-sensitivity in several resistant cases. Yet, clinical applications of tannic acid have been limited owing to its poor lipid solubility, low bioavailability, off-taste, and short half-life. To overcome such obstacles, novel drug delivery systems have been employed to deliver tannic acid with the aim of improving its applications and/or efficacy against cancer cells. Among these drug delivery systems are several types of organic and metallic nanoparticles. In this review, the authors focus on the molecular mechanisms of tannic acid in tuning several neoplastic diseases as well as novel drug delivery systems that can be used for its clinical applications with an attempt to provide a systemic reference to promote the development of tannic acid as a cheap drug and/or drug delivery system in cancer management.

Inflammageing in the cardiovascular system: mechanisms, emerging targets, and novel therapeutic strategies

2020 ◽  
Vol 134 (17) ◽  
pp. 2243-2262
Author(s):  
Danlin Liu ◽  
Gavin Richardson ◽  
Fehmi M. Benli ◽  
Catherine Park ◽  
João V. de Souza ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Cardiovascular System ◽  
Nlrp3 Inflammasome ◽  
Molecular Mechanisms ◽  
Molecular Targets ◽  
Therapeutic Interventions ◽  
Low Grade ◽  
Cardiovascular Research ◽  
Inflammatory Processes ◽  
Ach Receptors

Abstract In the elderly population, pathological inflammation has been associated with ageing-associated diseases. The term ‘inflammageing’, which was used for the first time by Franceschi and co-workers in 2000, is associated with the chronic, low-grade, subclinical inflammatory processes coupled to biological ageing. The source of these inflammatory processes is debated. The senescence-associated secretory phenotype (SASP) has been proposed as the main origin of inflammageing. The SASP is characterised by the release of inflammatory cytokines, elevated activation of the NLRP3 inflammasome, altered regulation of acetylcholine (ACh) nicotinic receptors, and abnormal NAD+ metabolism. Therefore, SASP may be ‘druggable’ by small molecule therapeutics targeting those emerging molecular targets. It has been shown that inflammageing is a hallmark of various cardiovascular diseases, including atherosclerosis, hypertension, and adverse cardiac remodelling. Therefore, the pathomechanism involving SASP activation via the NLRP3 inflammasome; modulation of NLRP3 via α7 nicotinic ACh receptors; and modulation by senolytics targeting other proteins have gained a lot of interest within cardiovascular research and drug development communities. In this review, which offers a unique view from both clinical and preclinical target-based drug discovery perspectives, we have focused on cardiovascular inflammageing and its molecular mechanisms. We have outlined the mechanistic links between inflammageing, SASP, interleukin (IL)-1β, NLRP3 inflammasome, nicotinic ACh receptors, and molecular targets of senolytic drugs in the context of cardiovascular diseases. We have addressed the ‘druggability’ of NLRP3 and nicotinic α7 receptors by small molecules, as these proteins represent novel and exciting targets for therapeutic interventions targeting inflammageing in the cardiovascular system and beyond.

Novel drug delivery approaches in treating pulmonary fibrosis

2018 ◽  
Vol 60 (4) ◽  
Author(s):  
Kamal Dua ◽  
Rajendra Awasthi ◽  
Jyotsana R. Madan ◽  
Dinesh K. Chellappan ◽  
Buchi N. Nalluri ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Pulmonary Fibrosis ◽  
Novel Drug

Update Treatment for Prolactinoma

2018 ◽  
Vol 3 (06) ◽  
Author(s):  
Chávez Hernández María Margarita ◽  
Jiménez Báez María Valeria ◽  
Armijo Medina María Fernanda ◽  
Domínguez Leyva Jorge Miguel ◽  
Góngora Valencia Karen Alejandra ◽  
...  
Keyword(s):  
Dopamine Agonist ◽  
Safety Profile ◽  
Pituitary Tumor ◽  
Common Type ◽  
Treatment Modalities ◽  
First Line ◽  
Agonist Therapy ◽  
Dopamine Agonist Therapy ◽  
Gonadal Dysfunction

Prolactinomas are the most common type of functional pituitary tumor. The present manuscript is an update on the treatment modalities for prolactinomas. Effective hyperprolactinemia treatment is of great importance, due to its potential deleterious effects including infertility, gonadal dysfunction and osteoporosis. Dopamine agonist therapy is the first line of treatment for prolactinomas; recurrence of disease after cessation of the drug may occur in patients. Its safety profile remains high, allowing its use during pregnancy.

A Review on Fast Dissolving Tablet

2017 ◽  
Vol 8 (03) ◽  
Author(s):  
Sagar T. Malsane ◽  
Smita S. Aher ◽  
R. B. Saudagar
Keyword(s):  
Drug Delivery ◽  
Patient Compliance ◽  
Research Area ◽  
Oral Route ◽  
Dosage Forms ◽  
The Novel ◽  
The Past ◽  
Orally Disintegrating Tablets ◽  
Novel Drug ◽  
Experience Difficulty

Oral route is presently the gold standard in the pharmaceutical industry where it is regarded as the safest, most economical and most convenient method of drug delivery resulting in highest patient compliance. Over the past three decades, orally disintegrating tablets (FDTs) have gained considerable attention due to patient compliance. Usually, elderly people experience difficulty in swallowing the conventional dosage forms like tablets, capsules, solutions and suspensions because of tremors of extremities and dysphagia. In some cases such as motion sickness, sudden episodes of allergic attack or coughing, and an unavailability of water, swallowing conventional tablets may be difficult. One such problem can be solved in the novel drug delivery system by formulating “Fast dissolving tablets” (FDTs) which disintegrates or dissolves rapidly without water within few seconds in the mouth due to the action of superdisintegrant or maximizing pore structure in the formulation. The review describes the various formulation aspects, superdisintegrants employed and technologies developed for FDTs, along with various excipients, evaluation tests, marketed formulation and drugs used in this research area.

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