Evaluation of BBB permeable nucleolipid (NLDPU): A di-C15-ketalised palmitone appended uridine as neuro-tracer for SPECT

Swastika,; Chaturvedi, Shubhra; Kaul, Ankur; Hazari, Puja Panwar; Jha, Preeti; Pal, Sunil; Singh, B.; Barthélémy, Philippe; Mishra, Anil K.

doi:10.1016/j.ijpharm.2019.04.074

Cited by 10 publications

(2 citation statements)

References 40 publications

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“…Oil-in-water (O/W) NEs, made of submicrometric oily droplets stabilized by a corona of amphiphilic surfactants, present enhanced stability compared to other nanosystems and high loading capacity of hydrophobic drugs or imaging probes. ,− Very recently it has also been reported that some NLs, such as an NL radiotracer, were successfully able to permeate the BBB, suggesting that NLs could be promising absorption promoters. In this work, original NEs associated with nucleolipids were developed to enhance the membrane-crossing properties for therapeutic purposes and particularly in the context of neurodegenerative diseases.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Intracellular Uptake of Rhodamine–Nucleolipid Conjugates into a Nanoemulsion Vehicle

et al. 2020

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Neurodegenerative diseases represent some of the greatest challenges for both basic science and clinical medicine. Due to their prevalence and the lack of known biochemical-based treatments, these complex pathologies result in an increasing societal cost. Increasing genetic and neuropathological evidence indicates that lysosomal impairment may be a common factor linking these diseases, demanding the development of therapeutic strategies aimed at restoring the lysosomal function. Here, we propose the design and synthesis of a nucleolipid conjugate as a nonviral chemical nanovector to specifically target neuronal cells and intracellular organelles. Herein, thymidine, appropriately substituted to increase its lipophilicity, was used as a model nucleoside and a fluorophore moiety, covalently bound to the nucleoside, allowed the monitoring of nucleolipid internalization in vitro. To improve nucleolipid protection and cellular uptake, these conjugates were formulated in nanoemulsions. In vitro biological assays demonstrated cell uptake-and internalization-associated colocalization with lysosomal markers. Overall, this nucleolipid− nanoemulsion-based formulation represents a promising drug-delivery tool to target the central nervous system, able to deliver drugs to restore the impaired lysosomal function.

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Section: Introductionmentioning

confidence: 99%

Synthesis and Intracellular Uptake of Rhodamine–Nucleolipid Conjugates into a Nanoemulsion Vehicle

et al. 2020

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“…It is widely accepted that NLs are efficient molecular carriers for the delivery of therapeutic ingredients (Simeone et al, 2011), (Benizri et al, 2018), (Zhou et al, 2020). Their ability to cross the BBB was also recently highlighted (Swastika et al, 2019), making them good candidates for our goal. Based on this outcome, it was first demonstrated that a NL appropriately functionalized could be loaded in an O/W NE and subsequently efficiently internalized within human neuronal cells and co-localized with targeted lysosomes (Cunha et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Nucleolipid Acid-Based Nanocarriers Restore Neuronal Lysosomal Acidification Defects

et al. 2021

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Increasing evidence suggests that lysosomal dysfunction has a pathogenic role in neurodegenerative diseases. In particular, an increase in lysosomal pH has been reported in different cellular models of Parkinson’s disease. Thus, targeting lysosomes has emerged as a promising approach. More specifically, regulating its pH could play a central role against the neurodegeneration process. To date, only a few agents specifically targeting lysosomal pH are reported in the literature, partly due to the challenge of crossing the Blood-Brain-Barrier (BBB), preventing drug penetration into the central nervous system (CNS). To develop chronic treatments for neurodegenerative diseases, crossing the BBB is crucial. We report herein the conception and synthesis of an innovative DNA derivative-based nanocarrier. Nucleolipids, carrying a biocompatible organic acid as an active ingredient, were designed and synthesized as prodrugs. They were successfully incorporated into an oil-in-water nanoemulsion vehicle to cross biological membranes and then release effectively biocompatible acidic components to restore the functional lysosomal pH of neuronal cells. Biological assays on a genetic cell model of Parkinson’s disease highlighted the non-toxicity of such nucleolipids after cellular uptake and their ability (at c = 40 µM) to fully restore lysosomal acidity.

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Novel dicationic pyrimidine-based nucleolipid bearing piperidine head groups: Synthesis, aggregation behavior, solubilization capacity and interaction with DNA decamer

Gabdrakhmanov

Kuznetsova

Saifina

et al. 2020

Colloids and Surfaces A: Physicochemical and Engineering Aspect

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Evaluation of BBB permeable nucleolipid (NLDPU): A di-C15-ketalised palmitone appended uridine as neuro-tracer for SPECT

Cited by 10 publications

References 40 publications

Synthesis and Intracellular Uptake of Rhodamine–Nucleolipid Conjugates into a Nanoemulsion Vehicle

Synthesis and Intracellular Uptake of Rhodamine–Nucleolipid Conjugates into a Nanoemulsion Vehicle

Nucleolipid Acid-Based Nanocarriers Restore Neuronal Lysosomal Acidification Defects

Novel dicationic pyrimidine-based nucleolipid bearing piperidine head groups: Synthesis, aggregation behavior, solubilization capacity and interaction with DNA decamer

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