Dual-targeting for brain-specific drug delivery: synthesis and biological evaluation

Abstract Ibuprofen is one of the most potent non-steroid anti-inflammatory drugs (NSAIDs) and plays an important role in the treatment of neurodegenerative diseases. However, its poor brain penetration and serious side effects at therapeutic doses, has hindered its further application. Thus, it is of great interest to develop a carrier-mediated transporter (CMT) system that is capable of more efficiently delivering ibuprofen into the brain at smaller doses to treat neurodegenerative diseases. In this study, a dual-mediated ibuprofen prodrug modified by glucose (Glu) and vitamin C (Vc) for central nervous system (CNS) drug delivery was designed and synthesized in order to effectively deliver ibuprofen to brain. Ibuprofen could be released from the prepared prodrugs when incubated with various buffers, mice plasma and brain homogenate. Also, the prodrug showed superior neuroprotective effect in vitro and in vivo than ibuprofen. Our results suggest that chemical modification of therapeutics with warheads of glucose and Vc represents a promising and efficient strategy for the development of brain-targeting prodrugs by utilizing the endogenous transportation mechanism of the warheads.

• Publication year

  2018

• Venue

  Drug Delivery

• Publication date

  2018-01-01

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1080/10717544.2018.1431978PMID 29382239PMCID 6058731
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Surface functionalized exosomes as targeted drug delivery vehicles for cerebral ischemia therapy.

  2018cited by this paper
• GLUT1‐mediated venlafaxine‐thiamine disulfide system‐glucose conjugates with “lock‐in” function for central nervous system delivery

  2018cited by this paper
• Design, Synthesis and Evaluation of Dual-targeting Prodrug Co-modified by Organic Amine and L-ascorbic Acid for CNS Delivery

  2017cited by this paper
• Blood-brain barrier dysfunction induced by silica NPs in vitro and in vivo: Involvement of oxidative stress and Rho-kinase/JNK signaling pathways.

  2017cited by this paper
• Pyrilamine‐sensitive proton‐coupled organic cation (H+/OC) antiporter for brain‐specific drug delivery

  2017cited by this paper
• Dual-modified liposome codelivery of doxorubicin and vincristine improve targeting and therapeutic efficacy of glioma

  2017cited by this paper
• Nanoparticle-mediated brain drug delivery: Overcoming blood-brain barrier to treat neurodegenerative diseases.

  2016cited by this paper
• Ibuprofen or piroxicam protects nigral neurons and delays the development of l-dopa induced dyskinesia in rats with experimental Parkinsonism: Influence on angiogenesis.

  2016cited by this paper
• Novel anionic polymer as a carrier for CNS delivery of anti-Alzheimer drug

  2016cited by this paper
• Oleic acid derivative of polyethylenimine-functionalized proliposomes for enhancing oral bioavailability of extract of Ginkgo biloba

  2016cited by this paper
• Novel flurbiprofen derivatives with improved brain delivery: synthesis, in vitro and in vivo evaluations

  2016cited by this paper
• Design, synthesis and biological evaluation of multivalent glucosides with high affinity as ligands for brain targeting liposomes.

  2014cited by this paper
• Design, synthesis and biological evaluation of brain targeting l-ascorbic acid prodrugs of ibuprofen with "lock-in" function.

  2014cited by this paper
• Design, synthesis and preliminary biological evaluation of brain targeting l-ascorbic acid prodrugs of ibuprofen

  2013cited by this paper
• Design, synthesis and biological evaluation of brain-specific glucosyl thiamine disulfide prodrugs of naproxen.

  2011cited by this paper
• Synthesis, in vitro and in vivo characterization of glycosyl derivatives of ibuprofen as novel prodrugs for brain drug delivery

  2009cited by this paper
• Physiology and pharmacological role of the blood-brain barrier.

  2008cited by this paper
• Progress in Drug Delivery to the Central Nervous System by the Prodrug Approach

  2008cited by this paper

• The Dopaminergic and Anti-Neuroinflammatory Properties of Functionalized Nanoliposomes Containing Levodopa and Ibuprofen and Conjugated with Anti-Alpha-Synuclein Aptamer

  2025cites this paper
• Prodrugs and their activation mechanisms for brain drug delivery

  2025cites this paper
• Current status and advances to improving drug delivery in diffuse intrinsic pontine glioma.

  2024cites this paper
• Fo-Shou-San Ameliorates Chronic Cerebral Hypoperfusion-Induced Cognitive Impairment in Mice by Regulating NRF2/HO-1 Pathway Against Ferroptosis.

  2023cites this paper
• Non-Invasive Drug Delivery across the Blood–Brain Barrier: A Prospective Analysis

  2023cites this paper
• Medulloblastoma targeted therapy: From signaling pathways heterogeneity and current treatment dilemma to the recent advances in development of therapeutic strategies.

  2023cites this paper
• Application of ionic liquid to enhance the nose-to-brain delivery of etodolac.

  2022cites this paper
• Increased/Targeted Brain (Pro)Drug Delivery via Utilization of Solute Carriers (SLCs)

  2022cites this paper
• Current Update on Transcellular Brain Drug Delivery

  2022cites this paper
• Astragalus Polysaccharide Alleviates Constipation in the Elderly Via Modification of Gut Microbiota and Fecal Metabolism

  2022cites this paper
• Targeting Transporters for Drug Delivery to the Brain: Can We Do Better?

  2022influential citation
• Cysteine Donor-Based Brain-Targeting Prodrug: Opportunities and Challenges

  2022cites this paper
• Asiaticoside alleviates cardiomyocyte apoptosis and oxidative stress in myocardial ischemia/reperfusion injury via activating the PI3K-AKT-GSK3β pathway in vivo and in vitro

  2021cites this paper
• Novel Multifunctional Ascorbic Triazole Derivatives for Amyloidogenic Pathway Inhibition, Anti-Inflammation, and Neuroprotection

  2021cites this paper
• The Protective Effect of Aspirin Eugenol Ester on Oxidative Stress to PC12 Cells Stimulated with H2O2 through Regulating PI3K/Akt Signal Pathway

  2021cites this paper
• Multi-disciplinary Approach for Drug and Gene Delivery Systems to the Brain

  2021cites this paper
• The Protective Effect of Aspirin Eugenol Ester on Paraquat-Induced Acute Liver Injury Rats

  2020cites this paper
• Development, Characterization, and Pharmacological Investigation of Sesamol and Thymol Conjugates of Mefenamic Acid

  2020cites this paper
• Nanocarriers for Successful Drug Delivery Across Blood-Brain Barrier

  2020cites this paper
• Biotin and glucose co-modified multi-targeting liposomes for efficient delivery of chemotherapeutics for the treatment of glioma.

  2020cites this paper
• Evaluation of the binding properties of drugs to albumin from DSC thermograms.

  2020cites this paper
• Liposomes actively recognizing the glucose transporter GLUT1 and integrin αvβ3 for dual‐targeting of glioma

  2019cites this paper
• Dual-targeting liposomes with active recognition of GLUT5 and αvβ3 for triple-negative breast cancer.

  2019cites this paper
• Dual-targeting for brain-specific liposomes drug delivery system: Synthesis and preliminary evaluation.

  2018cites this paper
• Pyrilamine‐sensitive proton‐coupled organic cation (H+/OC) antiporter for brain‐specific drug delivery

  2017cites this paper