The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
Indirect Evidence that Drug Brain Targeting Using Polysorbate 80-Coated Polybutylcyanoacrylate Nanoparticles Is Related to Toxicity
Abstract
Purpose To investigate the mechanism underlying the entry of the analgesic peptide dalargin into brain using biodegradable polybutylcyanoacrylate (PBCA) nanoparticles (NP) overcoated with polysorbate 80.Methods The investigations were carried out with PBCA NP and with non biodegradable polystyrene (PS) NP (200 nm diameter). Dalargin adsorption was assessed by HPLC. Its entry into the CNS in mice was evaluated using the tail-flick procedure. Locomotor activity measurements were performed to compare NP toxicities. BBB permeabilization by PBCA NP was studied in vitro using a coculture of bovine brain capillary endothelial cells and rat astrocytes.Results Dalargin loading was 11.7 microg/mg on PBCA NP and 16.5 microg/ mg on PS NP. Adding polysorbate 80 to NP led to a complete desorption. Nevertheless, dalargin associated with PBCA NP and polysorbate 80 induced a potent and prolonged analgesia, which could not be obtained using PS NP in place of PBCA NP. Locomotor activity dramatically decreased in mice dosed with PBCA NP, but not with PS NP. PBCA NP also caused occasional mortality. In vitro, PBCA NP (10 microg/ml) induced a permeabilization of the BBB model.Conclusions A non specific permeabilization of the BBB, probably related to the toxicity of the carrier, may account for the CNS penetration of dalargin associated with PBCA NP and polysorbate 80.
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“Several studies suggest that nanoparticles of any material may create specific biodistribution and toxicological profiles [95].”
From Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier (2011) · cites this paper as [95]
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Metadata
- Authors
- Olivier, J.-C., Fenart, L., Chauvet, R., Pariat, C., Cecchelli, R., & Couet, W.
- Affiliations
- Université de Poitiers (FR)
- Université de Rennes (FR)
- Corresponding author
- Olivier, Jean-Christophe
- Venue
- Pharmaceutical Research
- Published
- 1999-12
- Volume
- 16
- Issue
- 12
- Pages
- 1836-1842
- ISSN
- 0724-8741 (ISSN-L)
- 1573-904X
- OpenAlex
- W1526328115
- Cited by
- 213
- References
- 28
- Citations by year
- 2025: 2 · 2024: 8 · 2023: 5 · 2022: 4 · 2021: 3 · 2020: 9 · 2019: 7 · 2018: 6 · 2017: 4 · 2016: 12 · 2015: 9 · 2014: 9 · 2013: 15 · 2012: 14
- FWCI
- 4.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Pharmaceutical Research (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- dalargin, polybutylcyanoacrylate nanoparticles, Tween 80, brain drug delivery, blood-brain barrier permeabilization, analgesic peptides, nanoparticle toxicity, polystyrene nanoparticles, brain microvascular endothelial cells, astrocytes, locomotor activity
- MeSH terms
- Analgesics, Animals, Blood-Brain Barrier, Brain, Cells, Cultured, Chromatography, High Pressure Liquid, Enbucrilate, Endothelium, Excipients, Male, Microspheres, Motor Activity, Pain Measurement, Polysorbates, Enkephalin, Leucine-2-Alanine, Mice
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