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

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.

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.

scholarly journals Systemic delivery of blood–brain barrier-targeted polymeric nanoparticles enhances delivery to brain tissue

2015 ◽  
Vol 23 (7-8) ◽  
pp. 736-749 ◽  
Author(s):  
Jennifer K. Saucier-Sawyer ◽  
Yang Deng ◽  
Young-Eun Seo ◽  
Christopher J. Cheng ◽  
Junwei Zhang ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Blood Brain Barrier ◽  
Polymeric Nanoparticles ◽  
Brain Barrier ◽  
Systemic Delivery ◽  
Blood Brain

scholarly journals Development of Polymeric Nanoparticles for Blood–Brain Barrier Transfer—Strategies and Challenges

2021 ◽  
pp. 2003937
Author(s):  
Weisen Zhang ◽  
Ami Mehta ◽  
Ziqiu Tong ◽  
Lars Esser ◽  
Nicolas H. Voelcker
Keyword(s):  
Blood Brain Barrier ◽  
Polymeric Nanoparticles ◽  
Brain Barrier ◽  
Blood Brain ◽  
Transfer Strategies

scholarly journals Drug Delivery to The Brain Using Polymeric Nanoparticles: A Review

2013 ◽  
Vol 2 (3) ◽  
pp. 107-132 ◽  
Author(s):  
Bhatt Neha ◽  
Bhatt Ganesh ◽  
Kothiyal Preeti
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Polymeric Nanoparticles ◽  
Neurological Diseases ◽  
Drug Carriers ◽  
Brain Barrier ◽  
Pharmaceutical Drugs ◽  
Great Expectations ◽  
Cns Drug Delivery ◽  
Blood Brain

Nanoparticle drug carriers consist of solid biodegradable particles in size ranging from 10 to 1000 nm (50–300 nm generally). The use of minute particles as drug carriers for targeted treatment has been studied over a long period of time. A selective accumulation of active substances in target tissues has been demonstrated for certain so-called nanocarrier systems that are administered bound to pharmaceutical drugs. Great expectations are placed on nanocarrier systems that can overcome natural barriers such as the blood-brain barrier (BBB) and transport the medication directly to the desired tissue and thus heal neurological diseases that were formerly incurable. Polymeric Nanoparticle have been shown to be promising carriers for CNS drug delivery due to their potential both in encapsulating drugs, hence protecting them from excretion and metabolism, and in delivering active agents across the blood – brain barrier without inflicting any damage to the barrier. Different polymers have been used and different strategies like surface modification have been done to increase the retention time of nanoparticles. DOI: http://dx.doi.org/10.3329/ijpls.v2i3.15457 International Journal of Pharmaceutical and Life Sciences Vol.2(3) 2013: 107-132

scholarly journals Paracrine signalling of inflammatory cytokines from an in vitro blood brain barrier model upon exposure to polymeric nanoparticles

The Analyst ◽  
2014 ◽  
Vol 139 (5) ◽  
pp. 923-930 ◽  
Author(s):  
Michelle Nic Raghnaill ◽  
Mattia Bramini ◽  
Dong Ye ◽  
Pierre-Olivier Couraud ◽  
Ignacio A. Romero ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Inflammatory Cytokines ◽  
Polymeric Nanoparticles ◽  
Brain Barrier ◽  
Paracrine Signalling ◽  
Blood Brain ◽  
Blood Brain Barrier Model ◽  
Barrier Model

Potential Use of Polymeric Nanoparticles for Drug Delivery Across the Blood-Brain Barrier

2013 ◽  
Vol 999 (999) ◽  
pp. 1-6 ◽  
Author(s):  
G. Tosi ◽  
B. Bortot ◽  
B. Ruozi ◽  
D. Dolcetta ◽  
M.A. Vandelli ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Polymeric Nanoparticles ◽  
Brain Barrier ◽  
Blood Brain ◽  
Potential Use

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.

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