PLGA nanoparticles prepared by nano-emulsion templating using low-energy methods as efficient nanocarriers for drug delivery across the blood–brain barrier

2015 ◽  
Vol 211 ◽  
pp. 134-143 ◽  
Author(s):  
C. Fornaguera ◽  
A. Dols-Perez ◽  
G. Calderó ◽  
M.J. García-Celma ◽  
J. Camarasa ◽  
...  
2013 ◽  
Vol 2 (3) ◽  
pp. 241-257 ◽  
Author(s):  
Jingyan Li ◽  
Cristina Sabliov

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.


Nanoscale ◽  
2015 ◽  
Vol 7 (28) ◽  
pp. 12076-12084 ◽  
Author(s):  
C. Fornaguera ◽  
N. Feiner-Gracia ◽  
G. Calderó ◽  
M. J. García-Celma ◽  
C. Solans

Schematic representation of the methodology used in this study to prepare GAL-loaded PLGA nanoparticles from nano-emulsion templating: nano-emulsification using the PIC low-energy method followed by solvent evaporation.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 500
Author(s):  
Kaining Zhi ◽  
Babatunde Raji ◽  
Anantha R. Nookala ◽  
Mohammad Moshahid Khan ◽  
Xuyen H. Nguyen ◽  
...  

The blood–brain barrier (BBB) is a natural obstacle for drug delivery into the human brain, hindering treatment of central nervous system (CNS) disorders such as acute ischemic stroke, brain tumors, and human immunodeficiency virus (HIV)-1-associated neurocognitive disorders. Poly(lactic-co-glycolic acid) (PLGA) is a biocompatible polymer that is used in Food and Drug Administration (FDA)-approved pharmaceutical products and medical devices. PLGA nanoparticles (NPs) have been reported to improve drug penetration across the BBB both in vitro and in vivo. Poly(ethylene glycol) (PEG), poly(vinyl alcohol) (PVA), and poloxamer (Pluronic) are widely used as excipients to further improve the stability and effectiveness of PLGA formulations. Peptides and other linkers can be attached on the surface of PLGA to provide targeting delivery. With the newly published guidance from the FDA and the progress of current Good Manufacturing Practice (cGMP) technologies, manufacturing PLGA NP-based drug products can be achieved with higher efficiency, larger quantity, and better quality. The translation from bench to bed is feasible with proper research, concurrent development, quality control, and regulatory assurance.


2020 ◽  
Vol 26 (37) ◽  
pp. 4721-4737 ◽  
Author(s):  
Bhumika Kumar ◽  
Mukesh Pandey ◽  
Faheem H. Pottoo ◽  
Faizana Fayaz ◽  
Anjali Sharma ◽  
...  

Parkinson’s disease is one of the most severe progressive neurodegenerative disorders, having a mortifying effect on the health of millions of people around the globe. The neural cells producing dopamine in the substantia nigra of the brain die out. This leads to symptoms like hypokinesia, rigidity, bradykinesia, and rest tremor. Parkinsonism cannot be cured, but the symptoms can be reduced with the intervention of medicinal drugs, surgical treatments, and physical therapies. Delivering drugs to the brain for treating Parkinson’s disease is very challenging. The blood-brain barrier acts as a highly selective semi-permeable barrier, which refrains the drug from reaching the brain. Conventional drug delivery systems used for Parkinson’s disease do not readily cross the blood barrier and further lead to several side-effects. Recent advancements in drug delivery technologies have facilitated drug delivery to the brain without flooding the bloodstream and by directly targeting the neurons. In the era of Nanotherapeutics, liposomes are an efficient drug delivery option for brain targeting. Liposomes facilitate the passage of drugs across the blood-brain barrier, enhances the efficacy of the drugs, and minimize the side effects related to it. The review aims at providing a broad updated view of the liposomes, which can be used for targeting Parkinson’s disease.


2020 ◽  
Vol 26 (13) ◽  
pp. 1448-1465 ◽  
Author(s):  
Jozef Hanes ◽  
Eva Dobakova ◽  
Petra Majerova

Tauopathies are neurodegenerative disorders characterized by the deposition of abnormal tau protein in the brain. The application of potentially effective therapeutics for their successful treatment is hampered by the presence of a naturally occurring brain protection layer called the blood-brain barrier (BBB). BBB represents one of the biggest challenges in the development of therapeutics for central nervous system (CNS) disorders, where sufficient BBB penetration is inevitable. BBB is a heavily restricting barrier regulating the movement of molecules, ions, and cells between the blood and the CNS to secure proper neuronal function and protect the CNS from dangerous substances and processes. Yet, these natural functions possessed by BBB represent a great hurdle for brain drug delivery. This review is concentrated on summarizing the available methods and approaches for effective therapeutics’ delivery through the BBB to treat neurodegenerative disorders with a focus on tauopathies. It describes the traditional approaches but also new nanotechnology strategies emerging with advanced medical techniques. Their limitations and benefits are discussed.


2016 ◽  
Vol 15 (9) ◽  
pp. 1079-1091 ◽  
Author(s):  
Barbara Ruozi ◽  
Daniela Belletti ◽  
Francesca Pederzoli ◽  
Flavio Forni ◽  
Maria Angela Vandelli ◽  
...  

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii164-ii164
Author(s):  
Rianne Haumann ◽  
Fatma El-Khouly ◽  
Marjolein Breur ◽  
Sophie Veldhuijzen van Zanten ◽  
Gertjan Kaspers ◽  
...  

Abstract INTRODUCTION Chemotherapy has been unsuccessful for pediatric diffuse midline glioma (DMG) most likely due to an intact blood-brain barrier (BBB). However, the BBB has not been characterized in DMG and therefore its implications for drug delivery are unknown. In this study we characterized the BBB in DMG patients and compared this to healthy controls. METHODS End-stage DMG pontine samples (n=5) were obtained from the VUmc diffuse intrinsic pontine glioma (DIPG) autopsy study and age-matched healthy pontine samples (n=22) were obtained from the NIH NeuroBioBank. Tissues were stained for BBB markers claudin-5, zonula occludens-1, laminin, and PDGFRβ. Claudin-5 stains were used to determine vascular density and diameter. RESULTS In DMG, expression of claudin-5 was reduced and dislocated to the abluminal side of endothelial cells. In addition, the expression of zonula occludens-1 was reduced. The basement membrane protein laminin expression was reduced at the glia limitans in both pre-existent vessels and neovascular proliferation. PDGFRβ expression was not observed in DMG but was present in healthy pons. Furthermore, the number of blood vessels in DMG was significantly (P&lt; 0.01) reduced (13.9 ± 11.8/mm2) compared to healthy pons (26.3 ± 14.2/mm2). Markedly, the number of small blood vessels (&lt; 10µm) was significantly lower (P&lt; 0.01) while larger blood vessels (&gt; 10µm) were not significantly different (P= 0.223). The mean vascular diameter was larger for DMG 9.3 ± 9.9µm compared to 7.7 ± 9.0µm for healthy pons (P= 0.016). CONCLUSION Both the BBB and the vasculature are altered at end-stage DMG. The reduced vascular density might have implications for several drug delivery methods such as focused ultrasound and convection enhanced delivery that are being explored for the treatment of DMG. The functional effects of the structurally altered BBB remain unknown and further research is needed to evaluate the BBB integrity at end-stage DMG


Neuron ◽  
2014 ◽  
Vol 81 (1) ◽  
pp. 1-3 ◽  
Author(s):  
Robert D. Bell ◽  
Michael D. Ehlers

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