Glutathione conjugation dose-dependently increases brain-specific liposomal drug delivery in vitro and in vivo

Maussang, David; Rip, Jaap; Kregten, Joan van; Heuvel, Angelique van den; Pol, Susanne van der; Boom, Burt van der; Reijerkerk, Arie; Chen, Linda; Boer, Marco de; Gaillard, Pieter J.; Vries, Helga E. de

doi:10.1016/j.ddtec.2016.09.003

Cited by 76 publications

(38 citation statements)

References 43 publications

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“…PS 80 and F-68 have been previously shown to promote drug delivery across BBB by binding to endogenous apolipoproteins and interacting with lipoprotein receptors on BBB (30)(31)(32). GSH, a BBB shuttle peptide that has reached phase II clinical trials can transport NPs through BBB via GSH transporters (33,34).…”

Section: Resultsmentioning

confidence: 99%

BBB pathophysiology independent delivery of siRNA in traumatic brain injury

Qiu

et al. 2020

Preprint

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Small interfering RNA (siRNA) represents a powerful strategy to mitigate the long-term sequelae of traumatic brain injury (TBI). However, poor permeability of siRNA across the blood brain barrier (BBB) poses a major hurdle. One approach to overcome this challenge involves treatment administration while the BBB is physically breached post-injury. However, this approach is only applicable to a subset of injuries with substantial BBB breach and can lead to variable therapeutic response due to the heterogeneity of physical breaching of BBB in TBI. Moreover, since physical breaching of BBB is transient, this approach offers a limited window for therapeutic intervention, which is not ideal as repeated dosing beyond the transient window of physically breached BBB might be required. Herein, we report a nanoparticle platform for BBB pathophysiology-independent delivery of siRNA in TBI. We achieved this by combined modulation of surface chemistry and coating density, which maximized the active transport of nanoparticles across BBB. Intravenous injection of engineered nanoparticles, within or outside the window of physically breached BBB in TBI mice resulted in 3-fold higher brain accumulation compared to conventional PEGylated nanoparticles and demonstrated up to 50% gene silencing. To our knowledge, this is the first reported example of BBB pathophysiology-independent drug delivery in TBI, and the first time combined modulation of surface chemistry and coating density has been shown to tune BBB penetration of nanoparticles. Taken together, our approach offers a clinically relevant approach to develop siRNA therapeutics for preventing long-term effects of TBI and deserves further exploration.

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Section: Resultsmentioning

confidence: 99%

BBB pathophysiology independent delivery of siRNA in traumatic brain injury

Qiu

et al. 2020

Preprint

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“…The liposomes were prepared by the ethanol injection method, with cholesterol, mPEG-2000-1,2-distearoyl-sn-glycero-3-phosphoethanolamine, and different lipids: the brain accumulation was higher for egg-yolk phosphatidylcholine liposomes than 1,2-dimyristoyl-sn-glycero-3-phosphocholine liposomes. Maussang et al studied the mechanisms of increased in vivo brain delivery of the model drug ribavirin when encapsulated into PEGylated liposomes conjugated with GSH, intravenously administered to rats [ 142 ]. They demonstrated that this brain-specific uptake was positively correlated with increasing amounts of GSH coating and involved a receptor-mediated mechanism.…”

Section: Gsh Decoration As a Tool For Targeted Drug Delivery Systementioning

confidence: 99%

Glutathione: Antioxidant Properties Dedicated to Nanotechnologies

et al. 2018

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Which scientist has never heard of glutathione (GSH)? This well-known low-molecular-weight tripeptide is perhaps the most famous natural antioxidant. However, the interest in GSH should not be restricted to its redox properties. This multidisciplinary review aims to bring out some lesser-known aspects of GSH, for example, as an emerging tool in nanotechnologies to achieve targeted drug delivery. After recalling the biochemistry of GSH, including its metabolism pathways and redox properties, its involvement in cellular redox homeostasis and signaling is described. Analytical methods for the dosage and localization of GSH or glutathiolated proteins are also covered. Finally, the various therapeutic strategies to replenish GSH stocks are discussed, in parallel with its use as an addressing molecule in drug delivery.

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“…The results showed that the carboxifluorescein level in brain increased in liposomal formulation; in particular, the GSH-PEG LP option made this level fourfold higher with respect to undecorated PEG LPs. The efficiency of GSH-PEG LP delivery in the brain was also tested for ribavirin drug (Rip et al, 2010;Maussang et al, 2016). The concentration of drug in brain tissue increased in modified LP formulation in Wistar rats after administration by intravenous route; the permeation rate beyond the BBB became proportional to the amount of GSH coating (ranging from 0 to 2%).…”

Section: Permeabilitymentioning

confidence: 99%

The New Frontiers in Neurodegenerative Diseases Treatment: Liposomal-Based Strategies

Cascione

Matteis

Leporatti

et al. 2020

Front. Bioeng. Biotechnol.

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In the last decade, the onset of neurodegenerative (ND) diseases is strongly widespread due to the age increase of the world population. Despite the intensive investigations boosted by the scientific community, an efficacious therapy has not been outlined yet. The drugs commonly used are only able to relieve symptom severity; following their oral or intravenous administration routes, their effectiveness is strictly limited due to their low ability to reach the Central Nervous System (CNS) overcoming the Blood Brain Barrier (BBB). Starting from these assumptions, the engineered-nanocarriers, such as lipid-nanocarriers, are suitable agents to enhance the delivery of drugs into the CNS due to their high solubility, bioavailability, and stability. Liposomal delivery systems are considered to be the ideal carriers, not only for conventional drugs but also for neuroprotective small molecules and green-extracted compounds. In the current work, the LP-based drug delivery improvements in in vivo applications against ND disorders were carefully assessed.

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Glutathione conjugation dose-dependently increases brain-specific liposomal drug delivery in vitro and in vivo

Cited by 76 publications

References 43 publications

BBB pathophysiology independent delivery of siRNA in traumatic brain injury

BBB pathophysiology independent delivery of siRNA in traumatic brain injury

Glutathione: Antioxidant Properties Dedicated to Nanotechnologies

The New Frontiers in Neurodegenerative Diseases Treatment: Liposomal-Based Strategies

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