Cited by 213Nanoparticle-Based Drug DeliveryAdvanced Drug Delivery SystemsBarrier Structure and Function Studies

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Indirect Evidence that Drug Brain Targeting Using Polysorbate 80-Coated Polybutylcyanoacrylate Nanoparticles Is Related to Toxicity

Olivier, Jean-Christophe, Fenart, Laurence, Chauvet, Romain, Pariat, Claudine, Cecchelli, Roméo, Couet, William·1999·Pharmaceutical Research

DOI 10.1023/a:1018947208597

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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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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
ORCID: Olivier, Jean-Christophe
Couet, William
Venue: Pharmaceutical Research
Publisher: Springer Science and Business Media LLC
Published: 1999-12
Volume: 16
Issue: 12
Pages: 1836-1842
ISSN: 0724-8741 (ISSN-L)
1573-904X
DOI: 10.1023/a:1018947208597
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: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
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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Indirect Evidence that Drug Brain Targeting Using Polysorbate 80-Coated Polybutylcyanoacrylate Nanoparticles Is Related to Toxicity

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