Novel Drug Delivery System for Curcumin: Implementation to Improve Therapeutic Efficacy against Neurological Disorders

2021 ◽  
Vol 24 ◽  
Author(s):  
Roohi Mohi-ud-din ◽  
Reyaz Hassan Mir ◽  
Taha Umair Wani ◽  
Abdul Jalil Shah ◽  
Ishtiyaq Mohi-Ud-Din ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Therapeutic Efficacy ◽  
Therapeutic Potential ◽  
Polymeric Nanoparticles ◽  
Curcuma Longa ◽  
Brain Barrier ◽  
Barrier Methods ◽  
Blood Brain ◽  
Toxicological Studies ◽  
Novel Drug

Background: Curcumin, a hydrophobic polyphenolic compound present in Curcuma longa Linn. (Turmeric), has been used to improve various neurodegenerative conditions, including Amyotrophic lateral sclerosis, Multiple Sclerosis, Parkinson's disease, Prion disease, stroke, anxiety, depression, and ageing. However, the blood-brain barrier (BBB) impedes the delivery of curcumin to the brain, as a result, limits its therapeutic potential. Objective/Aim: This review summarises the recent advances towards the therapeutic efficacy of curcumin along with various novel strategies to overcome its poor bioavailability across the blood-brain barrier. Methods: The collection of data for the compilation of this review work was searched in PubMed Scopus, Google Scholar, and Science Direct. Result: Various approaches have been opted to expedite the delivery of curcumin across the blood-brain barrier, including liposomes, micelles, polymeric nanoparticles, exosomes, dual targeting Nanoparticles etc. Conclusion: The review also summarises the numerous toxicological studies and the role of curcumin in CNS disorders.

scholarly journals Lipid polymeric nanoparticles modified with tight junction-modulating peptides promote afatinib delivery across a blood–brain barrier model

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yu-Li Lo ◽  
Hua-Ching Lin ◽  
Shu-Ting Hong ◽  
Chih-Hsien Chang ◽  
Chen-Shen Wang ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Tight Junction ◽  
Blood Brain Barrier ◽  
Polymeric Nanoparticles ◽  
Growth Factor Receptor ◽  
Brain Barrier ◽  
Polymeric Nanoparticle ◽  
Blood Brain ◽  
Blood Brain Barrier Model ◽  
Delivery Platform

Abstract Background Brain metastases from non-small cell lung cancer (NSCLC) remain one of the most challenging malignancies. Afatinib (Afa) is an orally administered irreversible ErbB family blocker approved for epidermal growth factor receptor (EGFR)-mutated NSCLC. However, the incidence of brain metastases in patients with NSCLC and EGFR mutation is high. One of the major obstacles in the treatment of brain metastases is to transport drugs across the blood–brain barrier (BBB). A lipid polymeric nanoparticle (LPN) modified with a tight junction-modulating peptide is a potential formulation to deliver therapeutics across the BBB. FD7 and CCD are short peptides that perturb the tight junctions (TJs) of the BBB. In this study, the use of LPN modified with FD7 or CCD as a delivery platform was explored to enhance Afa delivery across the BBB model of mouse brain-derived endothelial bEnd.3 cells. Results Our findings revealed that Afa/LPN-FD7 and Afa/LPN-CCD exhibited a homogeneous shape, a uniform nano-scaled particle size, and a sustained-release profile. FD7, CCD, Afa/LPN-FD7, and Afa/LPN-CCD did not cause a significant cytotoxic effect on bEnd.3 cells. Afa/LPN-FD7 and Afa/LPN-CCD across the bEnd.3 cells enhanced the cytotoxicity of Afa on human lung adenocarcinoma PC9 cells. FD7 and CCD-modulated TJ proteins, such as claudin 5 and ZO-1, reduced transendothelial electrical resistance, and increased the permeability of paracellular markers across the bEnd.3 cells. Afa/LPN-FD7 and Afa/LPN-CCD were also partially transported through clathrin- and caveolae-mediated transcytosis, revealing the effective activation of paracellular and transcellular pathways to facilitate Afa delivery across the BBB and cytotoxicity of Afa on PC9 cells. Conclusion TJ-modulating peptide-modified LPN could be a prospective platform for the delivery of chemotherapeutics across the BBB to the brain for the potential treatment of the BM of NSCLC.

scholarly journals Blood-Brain Barrier Damage in Ischemic Stroke and Its Regulation by Endothelial Mechanotransduction

2020 ◽  
Vol 11 ◽  
Author(s):  
Keqing Nian ◽  
Ian C. Harding ◽  
Ira M. Herman ◽  
Eno E. Ebong
Keyword(s):  
Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Neurovascular Unit ◽  
The United States ◽  
Brain Barrier ◽  
Endothelial Glycocalyx ◽  
Altered Expression ◽  
Blood Brain

Ischemic stroke, a major cause of mortality in the United States, often contributes to disruption of the blood-brain barrier (BBB). The BBB along with its supportive cells, collectively referred to as the “neurovascular unit,” is the brain’s multicellular microvasculature that bi-directionally regulates the transport of blood, ions, oxygen, and cells from the circulation into the brain. It is thus vital for the maintenance of central nervous system homeostasis. BBB disruption, which is associated with the altered expression of tight junction proteins and BBB transporters, is believed to exacerbate brain injury caused by ischemic stroke and limits the therapeutic potential of current clinical therapies, such as recombinant tissue plasminogen activator. Accumulating evidence suggests that endothelial mechanobiology, the conversion of mechanical forces into biochemical signals, helps regulate function of the peripheral vasculature and may similarly maintain BBB integrity. For example, the endothelial glycocalyx (GCX), a glycoprotein-proteoglycan layer extending into the lumen of bloods vessel, is abundantly expressed on endothelial cells of the BBB and has been shown to regulate BBB permeability. In this review, we will focus on our understanding of the mechanisms underlying BBB damage after ischemic stroke, highlighting current and potential future novel pharmacological strategies for BBB protection and recovery. Finally, we will address the current knowledge of endothelial mechanotransduction in BBB maintenance, specifically focusing on a potential role of the endothelial GCX.

scholarly journals Multiple blood-brain barrier transport mechanisms limit bumetanide accumulation, and therapeutic potential, in the mammalian brain

2017 ◽  
Vol 117 ◽  
pp. 182-194 ◽  
Author(s):  
Kerstin Römermann ◽  
Maren Fedrowitz ◽  
Philip Hampel ◽  
Edith Kaczmarek ◽  
Kathrin Töllner ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Therapeutic Potential ◽  
Brain Barrier ◽  
Mammalian Brain ◽  
Transport Mechanisms ◽  
Blood Brain ◽  
Multiple Blood

scholarly journals Novel drug-delivery approaches to the blood-brain barrier

2015 ◽  
Vol 31 (2) ◽  
pp. 257-264 ◽  
Author(s):  
Xiaoqing Wang ◽  
Xiaowen Yu ◽  
William Vaughan ◽  
Mingyuan Liu ◽  
Yangtai Guan
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain ◽  
Novel Drug

scholarly journals M01 as a novel drug enhancer for specifically targeting the blood-brain barrier.

2021 ◽  
Author(s):  
Olga Breitkreuz-Korff ◽  
Christian Tscheik ◽  
Giovanna Del Vecchio ◽  
Sophie Dithmer ◽  
Wolfgang Walther ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain ◽  
Novel Drug

PLA/PLGA nanoparticles for delivery of drugs across the blood-brain barrier

2013 ◽  
Vol 2 (3) ◽  
pp. 241-257 ◽  
Author(s):  
Jingyan Li ◽  
Cristina Sabliov
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Polymeric Nanoparticles ◽  
Drug Carrier ◽  
Plga Nanoparticles ◽  
Brain Barrier ◽  
Poly Lactic Acid ◽  
Blood Brain

AbstractThe blood-brain barrier (BBB), which protects the central nervous system (CNS) from unnecessary substances, is a challenging obstacle in the treatment of CNS disease. Many therapeutic agents such as hydrophilic and macromolecular drugs cannot overcome the BBB. One promising solution is the employment of polymeric nanoparticles (NPs) such as poly (lactic-co-glycolic acid) (PLGA) NPs as drug carrier. Over the past few years, significant breakthroughs have been made in developing suitable PLGA and poly (lactic acid) (PLA) NPs for drug delivery across the BBB. Recent advances on PLGA/PLA NPs enhanced neural delivery of drugs are reviewed in this paper. Both in vitro and in vivo studies are included. In these papers, enhanced cellular uptake and therapeutic efficacy of drugs delivered with modified PLGA/PLA NPs compared with free drugs or drugs delivered by unmodified PLGA/PLA NPs were shown; no significant in vitro cytotoxicity was observed for PLGA/PLA NPs. Surface modification of PLGA/PLA NPs by coating with surfactants/polymers or covalently conjugating the NPs with targeting ligands has been confirmed to enhance drug delivery across the BBB. Most unmodified PLGA NPs showed low brain uptake (<1%), which indirectly confirms the safety of PLGA/PLA NPs used for other purposes than treating CNS diseases.

Tailoring Lipid and Polymeric Nanoparticles as siRNA Carriers towards the Blood-Brain Barrier – from Targeting to Safe Administration

2016 ◽  
Vol 12 (1) ◽  
pp. 107-119 ◽  
Author(s):  
Maria João Gomes ◽  
Carlos Fernandes ◽  
Susana Martins ◽  
Fernanda Borges ◽  
Bruno Sarmento
Keyword(s):  
Blood Brain Barrier ◽  
Polymeric Nanoparticles ◽  
Brain Barrier ◽  
Blood Brain
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