Cell Uptake and Biocompatibility of Nanoparticles Prepared from Poly(benzyl malate) (Co)polymers Obtained through Chemical and Enzymatic Polymerization in Human HepaRG Cells and Primary Macrophages
The design of drug-loaded nanoparticles (NPs) appears to be a suitable strategy for the prolonged plasma concentration of therapeutic payloads, higher bioavailability, and the reduction of side effects compared with classical chemotherapies. In most cases, NPs are prepared from (co)polymers obtained...
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doaj-1c3b5f53867d45b296d87ec3f9f37eee2020-11-24T21:47:17ZengMDPI AGPolymers2073-43602018-11-011011124410.3390/polym10111244polym10111244Cell Uptake and Biocompatibility of Nanoparticles Prepared from Poly(benzyl malate) (Co)polymers Obtained through Chemical and Enzymatic Polymerization in Human HepaRG Cells and Primary MacrophagesHubert Casajus0Saad Saba1Manuel Vlach2Elise Vène3Catherine Ribault4Sylvain Tranchimand5Caroline Nugier-Chauvin6Eric Dubreucq7Pascal Loyer8Sandrine Cammas-Marion9Nicolas Lepareur10Ecole Nationale Supérieure de Chimie de Rennes, Univ Rennes, CNRS, ISCR, UMR 6226, F-35000 Rennes, FranceUniv Rennes, INSERM, INRA, Institut NUMECAN (Nutrition Metabolisms and Cancer) UMR_A 1341, UMR_S 1241, F-35000 Rennes, FranceUniv Rennes, INSERM, INRA, Institut NUMECAN (Nutrition Metabolisms and Cancer) UMR_A 1341, UMR_S 1241, F-35000 Rennes, FranceUniv Rennes, INSERM, INRA, Institut NUMECAN (Nutrition Metabolisms and Cancer) UMR_A 1341, UMR_S 1241, F-35000 Rennes, FranceUniv Rennes, INSERM, INRA, Institut NUMECAN (Nutrition Metabolisms and Cancer) UMR_A 1341, UMR_S 1241, F-35000 Rennes, FranceEcole Nationale Supérieure de Chimie de Rennes, Univ Rennes, CNRS, ISCR, UMR 6226, F-35000 Rennes, FranceEcole Nationale Supérieure de Chimie de Rennes, Univ Rennes, CNRS, ISCR, UMR 6226, F-35000 Rennes, FranceMontpellier SupAgro, INRA, CIRAD, Univ Montpellier, UMR 1208 IATE, F-34060 Montpellier, FranceUniv Rennes, INSERM, INRA, Institut NUMECAN (Nutrition Metabolisms and Cancer) UMR_A 1341, UMR_S 1241, F-35000 Rennes, FranceEcole Nationale Supérieure de Chimie de Rennes, Univ Rennes, CNRS, ISCR, UMR 6226, F-35000 Rennes, FranceUniv Rennes, INSERM, INRA, Institut NUMECAN (Nutrition Metabolisms and Cancer) UMR_A 1341, UMR_S 1241, F-35000 Rennes, FranceThe design of drug-loaded nanoparticles (NPs) appears to be a suitable strategy for the prolonged plasma concentration of therapeutic payloads, higher bioavailability, and the reduction of side effects compared with classical chemotherapies. In most cases, NPs are prepared from (co)polymers obtained through chemical polymerization. However, procedures have been developed to synthesize some polymers via enzymatic polymerization in the absence of chemical initiators. The aim of this work was to compare the acute in vitro cytotoxicities and cell uptake of NPs prepared from poly(benzyl malate) (PMLABe) synthesized by chemical and enzymatic polymerization. Herein, we report the synthesis and characterization of eight PMLABe-based polymers. Corresponding NPs were produced, their cytotoxicity was studied in hepatoma HepaRG cells, and their uptake by primary macrophages and HepaRG cells was measured. In vitro cell viability evidenced a mild toxicity of the NPs only at high concentrations/densities of NPs in culture media. These data did not evidence a higher biocompatibility of the NPs prepared from enzymatic polymerization, and further demonstrated that chemical polymerization and the nanoprecipitation procedure led to biocompatible PMLABe-based NPs. In contrast, NPs produced from enzymatically synthesized polymers were more efficiently internalized than NPs produced from chemically synthesized polymers. The efficient uptake, combined with low cytotoxicity, indicate that PMLABe-based NPs are suitable nanovectors for drug delivery, deserving further evaluation in vivo to target either hepatocytes or resident liver macrophages.https://www.mdpi.com/2073-4360/10/11/1244enzymatic polymerizationchemical polymerizationpoly(benzyl malate)biocompatible nanoparticlescell uptakecytotoxicityHepaRG cellshuman macrophages |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hubert Casajus Saad Saba Manuel Vlach Elise Vène Catherine Ribault Sylvain Tranchimand Caroline Nugier-Chauvin Eric Dubreucq Pascal Loyer Sandrine Cammas-Marion Nicolas Lepareur |
spellingShingle |
Hubert Casajus Saad Saba Manuel Vlach Elise Vène Catherine Ribault Sylvain Tranchimand Caroline Nugier-Chauvin Eric Dubreucq Pascal Loyer Sandrine Cammas-Marion Nicolas Lepareur Cell Uptake and Biocompatibility of Nanoparticles Prepared from Poly(benzyl malate) (Co)polymers Obtained through Chemical and Enzymatic Polymerization in Human HepaRG Cells and Primary Macrophages Polymers enzymatic polymerization chemical polymerization poly(benzyl malate) biocompatible nanoparticles cell uptake cytotoxicity HepaRG cells human macrophages |
author_facet |
Hubert Casajus Saad Saba Manuel Vlach Elise Vène Catherine Ribault Sylvain Tranchimand Caroline Nugier-Chauvin Eric Dubreucq Pascal Loyer Sandrine Cammas-Marion Nicolas Lepareur |
author_sort |
Hubert Casajus |
title |
Cell Uptake and Biocompatibility of Nanoparticles Prepared from Poly(benzyl malate) (Co)polymers Obtained through Chemical and Enzymatic Polymerization in Human HepaRG Cells and Primary Macrophages |
title_short |
Cell Uptake and Biocompatibility of Nanoparticles Prepared from Poly(benzyl malate) (Co)polymers Obtained through Chemical and Enzymatic Polymerization in Human HepaRG Cells and Primary Macrophages |
title_full |
Cell Uptake and Biocompatibility of Nanoparticles Prepared from Poly(benzyl malate) (Co)polymers Obtained through Chemical and Enzymatic Polymerization in Human HepaRG Cells and Primary Macrophages |
title_fullStr |
Cell Uptake and Biocompatibility of Nanoparticles Prepared from Poly(benzyl malate) (Co)polymers Obtained through Chemical and Enzymatic Polymerization in Human HepaRG Cells and Primary Macrophages |
title_full_unstemmed |
Cell Uptake and Biocompatibility of Nanoparticles Prepared from Poly(benzyl malate) (Co)polymers Obtained through Chemical and Enzymatic Polymerization in Human HepaRG Cells and Primary Macrophages |
title_sort |
cell uptake and biocompatibility of nanoparticles prepared from poly(benzyl malate) (co)polymers obtained through chemical and enzymatic polymerization in human heparg cells and primary macrophages |
publisher |
MDPI AG |
series |
Polymers |
issn |
2073-4360 |
publishDate |
2018-11-01 |
description |
The design of drug-loaded nanoparticles (NPs) appears to be a suitable strategy for the prolonged plasma concentration of therapeutic payloads, higher bioavailability, and the reduction of side effects compared with classical chemotherapies. In most cases, NPs are prepared from (co)polymers obtained through chemical polymerization. However, procedures have been developed to synthesize some polymers via enzymatic polymerization in the absence of chemical initiators. The aim of this work was to compare the acute in vitro cytotoxicities and cell uptake of NPs prepared from poly(benzyl malate) (PMLABe) synthesized by chemical and enzymatic polymerization. Herein, we report the synthesis and characterization of eight PMLABe-based polymers. Corresponding NPs were produced, their cytotoxicity was studied in hepatoma HepaRG cells, and their uptake by primary macrophages and HepaRG cells was measured. In vitro cell viability evidenced a mild toxicity of the NPs only at high concentrations/densities of NPs in culture media. These data did not evidence a higher biocompatibility of the NPs prepared from enzymatic polymerization, and further demonstrated that chemical polymerization and the nanoprecipitation procedure led to biocompatible PMLABe-based NPs. In contrast, NPs produced from enzymatically synthesized polymers were more efficiently internalized than NPs produced from chemically synthesized polymers. The efficient uptake, combined with low cytotoxicity, indicate that PMLABe-based NPs are suitable nanovectors for drug delivery, deserving further evaluation in vivo to target either hepatocytes or resident liver macrophages. |
topic |
enzymatic polymerization chemical polymerization poly(benzyl malate) biocompatible nanoparticles cell uptake cytotoxicity HepaRG cells human macrophages |
url |
https://www.mdpi.com/2073-4360/10/11/1244 |
work_keys_str_mv |
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1725898080367149056 |