ArticleJournal of controlled release : official journal of the Controlled Release Society2010
Stimuli-responsive star poly(ethylene glycol) drug conjugates for improved intracellular delivery of the drug in neuroinflammation.
Article in Journal of controlled release : official journal of the Controlled Release Society, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed, 61 citations in OpenAlex.
- Polymeric Nano Drug Delivery Systems for Overcoming Tumor Microenvironment-Mediated Drug Resistance.Pharmaceutics · 2026Review
- Precise intracellular uptake and endosomal release of diverse functional mRNA payloads via glutathione-responsive nanogels.Materials today. Bio · 2025Article
- Dendrimer nanotherapy targeting of glial dysfunction improves inflammation and neurobehavioral phenotype in adult female Mecp2-heterozygous mouse model of Rett syndrome.Journal of neurochemistry · 2024Article
- Development of a Potassium-Ion-Responsive Star Copolymer with Controlled Aggregation/Dispersion Transition.ACS omega · 2023Article
- Degradable redox-responsive disulfide-based nanogel drug carriers via dithiol oxidation polymerization.Biomaterials science · 2019Article
- Synthesis and In Vitro Evaluation of Polyethylene Glycol-Paclitaxel Conjugates for Lung Cancer Therapy.Pharmaceutical research · 2016Article
- Dendrimer nanocarriers for transport modulation across models of the pulmonary epithelium.Molecular pharmaceutics · 2015Article
- Dendrimer nanoscaffolds for potential theranostics of prostate cancer with a focus on radiochemistry.Molecular pharmaceutics · 2013Review
- Injectable PAMAM dendrimer-PEG hydrogels for the treatment of genital infections: formulation and in vitro and in vivo evaluation.Molecular pharmaceutics · 2011Article
- Synthesis of PEGylated lactose analogs for inhibition studies on T.cruzi trans-sialidase.Glycoconjugate journal · 2010Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
N-Acetyl cysteine (NAC) is a vital drug currently under clinical trials for the treatment of neuroinflammation in maternal-fetal applications. The free sulfhydryl groups in NAC lead to high plasma protein binding, resulting in low bioavailability. Preparation and activity of conjugates of NAC with thiol terminated multi-arm (6 and 8) poly(ethylene-glycol) (PEG) with disulfide linkages involving sulfhydryls of NAC are reported. Multiple copies (5 and 7) of NAC were conjugated on 6 and 8-arm-PEG respectively. Both the conjugates released 74% of NAC within 2h by thiol exchange reactions in the redox environment provided by glutathione (GSH) intracellularly (2-10mM). At physiological extracellular glutathione concentration (2 microM) both the conjugates were stable and did not release NAC. MTT assay showed comparable cell viability for unmodified PEGs and both the PEG-S-S-NAC conjugates. The conjugates were readily endocytosed by cells, as confirmed by flow cytometry and confocal microscopy. Efficacy of 6 and 8-arm-PEG-S-S-NAC conjugates was evaluated on activated microglial cells (the target cells, in vivo) by monitoring cytokine release in lipopolysaccharide (LPS) induced inflammatory response in microglial cells using the reactive oxygen species (ROS), free radical nitrile (NO), anti-inflammatory activity and GSH depletion. The conjugates showed significant increase in antioxidant activity (more than a factor of 2) compared to free drug as seen from the inhibition of LPS induced ROS, NO, GSH and tumor necrosis factor-alpha (TNF-alpha) release in microglial cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.