Skip to content
Back to outputs

Nanoparticles of alkylglyceryl-dextran-graft-poly(lactic acid) for drug delivery to the brain: preparation and in vitro investigation

Research output: Contribution to journalArticle

Standard

Nanoparticles of alkylglyceryl-dextran-graft-poly(lactic acid) for drug delivery to the brain : preparation and in vitro investigation. / Toman, Petr; Lien, Chun-Fu; Ahmad, Zeeshan; Dietrich, Susanne; Smith, James R.; An, Qian; Molnár, Éva; Pilkington, Geoffrey J.; Górecki, Darek C.; Tsibouklis, John; Barbu, Eugen.

In: Acta Biomaterialia, Vol. 23, No. 1, 01.09.2015, p. 250-262.

Research output: Contribution to journalArticle

Harvard

APA

Vancouver

Author

Bibtex

@article{5d1be715bd1b4590a93c424a3b6e95e4,
title = "Nanoparticles of alkylglyceryl-dextran-graft-poly(lactic acid) for drug delivery to the brain: preparation and in vitro investigation",
abstract = "Poly(lactic acid), which has an inherent tendency to form colloidal systems of low polydispersity, and alkylglyceryl-modified dextran – a material designed to combine the non-immunogenic and stabilising properties of dextran with the demonstrated permeation enhancing ability of alkylglycerols – have been combined for the development of nanoparticulate, blood–brain barrier-permeating, non-viral vectors. To this end, dextran, that had been functionalised via treatment with epoxide precursors of alkylglycerol, was covalently linked to poly(lactic acid) using a carbodiimide cross-linker to form alkylglyceryl-modified dextran-graft-poly(lactic acid). Solvent displacement and electrospray methods allowed the formulation of these materials into nanoparticles having a unimodal size distribution profile of about 100–200 nm and good stability at physiologically relevant pH (7.4). The nanoparticles were characterised in terms of hydrodynamic size (by Dynamic Light Scattering and Nanoparticle Tracking Analysis), morphology (by Scanning Electron Microscopy and Atomic Force Microscopy) and zeta potential, and their toxicity was evaluated using MTT and PrestoBlue assays. Cellular uptake was evidenced by confocal microscopy employing nanoparticles that had been loaded with the easy-to-detect Rhodamine B fluorescent marker. Transwell-model experiments employing mouse (bEnd3) and human (hCMEC/D3) brain endothelial cells revealed enhanced permeation (statistically significant for hCMEC/D3) of the fluorescent markers in the presence of the nanoparticles. Results of studies using Electric Cell Substrate Impedance Sensing suggested a transient decrease of the barrier function in an in vitro blood–brain barrier model following incubation with these nanoformulations. An in ovo study using 3-day chicken embryos indicated the absence of whole-organism acute toxicity effects. The collective in vitro data suggest that these alkylglyceryl-modified dextran-graft-poly(lactic acid) nanoparticles are promising candidates for in vivo evaluations that would test their capability to transport therapeutic actives to the brain.",
keywords = "WNU",
author = "Petr Toman and Chun-Fu Lien and Zeeshan Ahmad and Susanne Dietrich and Smith, {James R.} and Qian An and {\'E}va Moln{\'a}r and Pilkington, {Geoffrey J.} and G{\'o}recki, {Darek C.} and John Tsibouklis and Eugen Barbu",
year = "2015",
month = "9",
day = "1",
doi = "10.1016/j.actbio.2015.05.009",
language = "English",
volume = "23",
pages = "250--262",
journal = "Acta Biomaterialia",
issn = "1742-7061",
publisher = "Elsevier BV",
number = "1",

}

RIS

TY - JOUR

T1 - Nanoparticles of alkylglyceryl-dextran-graft-poly(lactic acid) for drug delivery to the brain

T2 - preparation and in vitro investigation

AU - Toman, Petr

AU - Lien, Chun-Fu

AU - Ahmad, Zeeshan

AU - Dietrich, Susanne

AU - Smith, James R.

AU - An, Qian

AU - Molnár, Éva

AU - Pilkington, Geoffrey J.

AU - Górecki, Darek C.

AU - Tsibouklis, John

AU - Barbu, Eugen

PY - 2015/9/1

Y1 - 2015/9/1

N2 - Poly(lactic acid), which has an inherent tendency to form colloidal systems of low polydispersity, and alkylglyceryl-modified dextran – a material designed to combine the non-immunogenic and stabilising properties of dextran with the demonstrated permeation enhancing ability of alkylglycerols – have been combined for the development of nanoparticulate, blood–brain barrier-permeating, non-viral vectors. To this end, dextran, that had been functionalised via treatment with epoxide precursors of alkylglycerol, was covalently linked to poly(lactic acid) using a carbodiimide cross-linker to form alkylglyceryl-modified dextran-graft-poly(lactic acid). Solvent displacement and electrospray methods allowed the formulation of these materials into nanoparticles having a unimodal size distribution profile of about 100–200 nm and good stability at physiologically relevant pH (7.4). The nanoparticles were characterised in terms of hydrodynamic size (by Dynamic Light Scattering and Nanoparticle Tracking Analysis), morphology (by Scanning Electron Microscopy and Atomic Force Microscopy) and zeta potential, and their toxicity was evaluated using MTT and PrestoBlue assays. Cellular uptake was evidenced by confocal microscopy employing nanoparticles that had been loaded with the easy-to-detect Rhodamine B fluorescent marker. Transwell-model experiments employing mouse (bEnd3) and human (hCMEC/D3) brain endothelial cells revealed enhanced permeation (statistically significant for hCMEC/D3) of the fluorescent markers in the presence of the nanoparticles. Results of studies using Electric Cell Substrate Impedance Sensing suggested a transient decrease of the barrier function in an in vitro blood–brain barrier model following incubation with these nanoformulations. An in ovo study using 3-day chicken embryos indicated the absence of whole-organism acute toxicity effects. The collective in vitro data suggest that these alkylglyceryl-modified dextran-graft-poly(lactic acid) nanoparticles are promising candidates for in vivo evaluations that would test their capability to transport therapeutic actives to the brain.

AB - Poly(lactic acid), which has an inherent tendency to form colloidal systems of low polydispersity, and alkylglyceryl-modified dextran – a material designed to combine the non-immunogenic and stabilising properties of dextran with the demonstrated permeation enhancing ability of alkylglycerols – have been combined for the development of nanoparticulate, blood–brain barrier-permeating, non-viral vectors. To this end, dextran, that had been functionalised via treatment with epoxide precursors of alkylglycerol, was covalently linked to poly(lactic acid) using a carbodiimide cross-linker to form alkylglyceryl-modified dextran-graft-poly(lactic acid). Solvent displacement and electrospray methods allowed the formulation of these materials into nanoparticles having a unimodal size distribution profile of about 100–200 nm and good stability at physiologically relevant pH (7.4). The nanoparticles were characterised in terms of hydrodynamic size (by Dynamic Light Scattering and Nanoparticle Tracking Analysis), morphology (by Scanning Electron Microscopy and Atomic Force Microscopy) and zeta potential, and their toxicity was evaluated using MTT and PrestoBlue assays. Cellular uptake was evidenced by confocal microscopy employing nanoparticles that had been loaded with the easy-to-detect Rhodamine B fluorescent marker. Transwell-model experiments employing mouse (bEnd3) and human (hCMEC/D3) brain endothelial cells revealed enhanced permeation (statistically significant for hCMEC/D3) of the fluorescent markers in the presence of the nanoparticles. Results of studies using Electric Cell Substrate Impedance Sensing suggested a transient decrease of the barrier function in an in vitro blood–brain barrier model following incubation with these nanoformulations. An in ovo study using 3-day chicken embryos indicated the absence of whole-organism acute toxicity effects. The collective in vitro data suggest that these alkylglyceryl-modified dextran-graft-poly(lactic acid) nanoparticles are promising candidates for in vivo evaluations that would test their capability to transport therapeutic actives to the brain.

KW - WNU

U2 - 10.1016/j.actbio.2015.05.009

DO - 10.1016/j.actbio.2015.05.009

M3 - Article

VL - 23

SP - 250

EP - 262

JO - Acta Biomaterialia

JF - Acta Biomaterialia

SN - 1742-7061

IS - 1

ER -

ID: 2354511