Tissue inhibitor of matrix metalloproteinases-1 loaded poly(lactic-co-glycolic acid) nanoparticles for delivery across the blood–brain barrier

Tissue inhibitor of matrix metalloproteinases-1 loaded poly(lactic-co-glycolic acid) nanoparticles for delivery across the blood–brain barrier

Mayank Chaturvedi,1 Yves Molino,2 Bojja Sreedhar,3 Michel Khrestchatisky,4 Leszek Kaczmarek1 1Laboratory of Neurobiology, Nencki Institute, Warsaw, Poland; 2Vect-Horus, Marseille, France; 3Indian Institute of Chemical Technology, Hyderabad, India; 4Aix-Marseille Université, CNRS, NICN, U...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Chaturvedi M, Molino Y, Sreedhar B, Khrestchatisky M, Kaczmarek L
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2014
Materias:
Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/8021733ddf8845aeaf4774a7b352d9fb
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:8021733ddf8845aeaf4774a7b352d9fb
record_format dspace
spelling oai:doaj.org-article:8021733ddf8845aeaf4774a7b352d9fb2021-12-02T04:20:58ZTissue inhibitor of matrix metalloproteinases-1 loaded poly(lactic-co-glycolic acid) nanoparticles for delivery across the blood–brain barrier1178-2013https://doaj.org/article/8021733ddf8845aeaf4774a7b352d9fb2014-01-01T00:00:00Zhttp://www.dovepress.com/tissue-inhibitor-of-matrix-metalloproteinases-1-loaded-polylactic-co-g-a15573https://doaj.org/toc/1178-2013 Mayank Chaturvedi,1 Yves Molino,2 Bojja Sreedhar,3 Michel Khrestchatisky,4 Leszek Kaczmarek1 1Laboratory of Neurobiology, Nencki Institute, Warsaw, Poland; 2Vect-Horus, Marseille, France; 3Indian Institute of Chemical Technology, Hyderabad, India; 4Aix-Marseille Université, CNRS, NICN, UMR7259, Marseille, France Aim: The aim of this study was to develop poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) for delivery of a protein – tissue inhibitor of matrix metalloproteinases 1 (TIMP-1) – across the blood–brain barrier (BBB) to inhibit deleterious matrix metalloproteinases (MMPs). Materials and methods: The NPs were formulated by multiple-emulsion solvent-evaporation, and for enhancing BBB penetration, they were coated with polysorbate 80 (Ps80). We compared Ps80-coated and uncoated NPs for their toxicity, binding, and BBB penetration on primary rat brain capillary endothelial cell cultures and the rat brain endothelial 4 cell line. These studies were followed by in vivo studies for brain delivery of these NPs. Results: Results showed that neither Ps80-coated nor uncoated NPs caused significant opening of the BBB, and essentially they were nontoxic. NPs without Ps80 coating had more binding to endothelial cells compared to Ps80-coated NPs. Penetration studies showed that TIMP-1 NPs + Ps80 had 11.21%±1.35% penetration, whereas TIMP-1 alone and TIMP-1 NPs without Ps80 coating did not cross the endothelial monolayer. In vivo studies indicated BBB penetration of intravenously injected TIMP-1 NPs + Ps80. Conclusion: The study demonstrated that Ps80 coating of NPs does not cause significant toxic effects to endothelial cells and that it can be used to enhance the delivery of protein across endothelial cell barriers, both in vitro and in vivo. Keywords: PLGA nanoparticles, drug delivery, protein delivery, sustained release, brain delivery, BBB penetration, RBCEC cultureChaturvedi MMolino YSreedhar BKhrestchatisky MKaczmarek LDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 575-588 (2014)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Chaturvedi M
Molino Y
Sreedhar B
Khrestchatisky M
Kaczmarek L
Tissue inhibitor of matrix metalloproteinases-1 loaded poly(lactic-co-glycolic acid) nanoparticles for delivery across the blood–brain barrier
description Mayank Chaturvedi,1 Yves Molino,2 Bojja Sreedhar,3 Michel Khrestchatisky,4 Leszek Kaczmarek1 1Laboratory of Neurobiology, Nencki Institute, Warsaw, Poland; 2Vect-Horus, Marseille, France; 3Indian Institute of Chemical Technology, Hyderabad, India; 4Aix-Marseille Université, CNRS, NICN, UMR7259, Marseille, France Aim: The aim of this study was to develop poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) for delivery of a protein – tissue inhibitor of matrix metalloproteinases 1 (TIMP-1) – across the blood–brain barrier (BBB) to inhibit deleterious matrix metalloproteinases (MMPs). Materials and methods: The NPs were formulated by multiple-emulsion solvent-evaporation, and for enhancing BBB penetration, they were coated with polysorbate 80 (Ps80). We compared Ps80-coated and uncoated NPs for their toxicity, binding, and BBB penetration on primary rat brain capillary endothelial cell cultures and the rat brain endothelial 4 cell line. These studies were followed by in vivo studies for brain delivery of these NPs. Results: Results showed that neither Ps80-coated nor uncoated NPs caused significant opening of the BBB, and essentially they were nontoxic. NPs without Ps80 coating had more binding to endothelial cells compared to Ps80-coated NPs. Penetration studies showed that TIMP-1 NPs + Ps80 had 11.21%±1.35% penetration, whereas TIMP-1 alone and TIMP-1 NPs without Ps80 coating did not cross the endothelial monolayer. In vivo studies indicated BBB penetration of intravenously injected TIMP-1 NPs + Ps80. Conclusion: The study demonstrated that Ps80 coating of NPs does not cause significant toxic effects to endothelial cells and that it can be used to enhance the delivery of protein across endothelial cell barriers, both in vitro and in vivo. Keywords: PLGA nanoparticles, drug delivery, protein delivery, sustained release, brain delivery, BBB penetration, RBCEC culture
format article
author Chaturvedi M
Molino Y
Sreedhar B
Khrestchatisky M
Kaczmarek L
author_facet Chaturvedi M
Molino Y
Sreedhar B
Khrestchatisky M
Kaczmarek L
author_sort Chaturvedi M
title Tissue inhibitor of matrix metalloproteinases-1 loaded poly(lactic-co-glycolic acid) nanoparticles for delivery across the blood–brain barrier
title_short Tissue inhibitor of matrix metalloproteinases-1 loaded poly(lactic-co-glycolic acid) nanoparticles for delivery across the blood–brain barrier
title_full Tissue inhibitor of matrix metalloproteinases-1 loaded poly(lactic-co-glycolic acid) nanoparticles for delivery across the blood–brain barrier
title_fullStr Tissue inhibitor of matrix metalloproteinases-1 loaded poly(lactic-co-glycolic acid) nanoparticles for delivery across the blood–brain barrier
title_full_unstemmed Tissue inhibitor of matrix metalloproteinases-1 loaded poly(lactic-co-glycolic acid) nanoparticles for delivery across the blood–brain barrier
title_sort tissue inhibitor of matrix metalloproteinases-1 loaded poly(lactic-co-glycolic acid) nanoparticles for delivery across the blood–brain barrier
publisher Dove Medical Press
publishDate 2014
url https://doaj.org/article/8021733ddf8845aeaf4774a7b352d9fb
work_keys_str_mv AT chaturvedim tissueinhibitorofmatrixmetalloproteinases1loadedpolylacticcoglycolicacidnanoparticlesfordeliveryacrossthebloodndashbrainbarrier
AT molinoy tissueinhibitorofmatrixmetalloproteinases1loadedpolylacticcoglycolicacidnanoparticlesfordeliveryacrossthebloodndashbrainbarrier
AT sreedharb tissueinhibitorofmatrixmetalloproteinases1loadedpolylacticcoglycolicacidnanoparticlesfordeliveryacrossthebloodndashbrainbarrier
AT khrestchatiskym tissueinhibitorofmatrixmetalloproteinases1loadedpolylacticcoglycolicacidnanoparticlesfordeliveryacrossthebloodndashbrainbarrier
AT kaczmarekl tissueinhibitorofmatrixmetalloproteinases1loadedpolylacticcoglycolicacidnanoparticlesfordeliveryacrossthebloodndashbrainbarrier
_version_ 1718401319429996544

Ejemplares similares