Chitosan-Based Nanogels: Synthesis and Toxicity Profile for Drug Delivery to Articular Joints

One important challenge in treating avascular-degraded cartilage is the development of new drugs for both pain management and joint preservation. Considerable efforts have been invested in developing nanosystems using biomaterials, such as chitosan, a widely used natural polymer exhibiting numerous...

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Main Authors: Seng Manivong, Araceli Garcia Ac, Shunmoogum A. Patten, Julio C. Fernandes, Mohamed Benderdour, Xavier Banquy, Florina Moldovan, Valérie Gaëlle Roullin
Format: Article
Language:English
Published: MDPI AG 2022-04-01
Series:Nanomaterials
Subjects:
Online Access:https://www.mdpi.com/2079-4991/12/8/1337
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author Seng Manivong
Araceli Garcia Ac
Shunmoogum A. Patten
Julio C. Fernandes
Mohamed Benderdour
Xavier Banquy
Florina Moldovan
Valérie Gaëlle Roullin
author_facet Seng Manivong
Araceli Garcia Ac
Shunmoogum A. Patten
Julio C. Fernandes
Mohamed Benderdour
Xavier Banquy
Florina Moldovan
Valérie Gaëlle Roullin
author_sort Seng Manivong
collection DOAJ
description One important challenge in treating avascular-degraded cartilage is the development of new drugs for both pain management and joint preservation. Considerable efforts have been invested in developing nanosystems using biomaterials, such as chitosan, a widely used natural polymer exhibiting numerous advantages, i.e., non-toxic, biocompatible and biodegradable. However, even if chitosan is generally recognized as safe, the safety and biocompatibility of such nanomaterials must be addressed because of potential for greater interactions between nanomaterials and biological systems. Here, we developed chitosan-based nanogels as drug-delivery platforms and established an initial biological risk assessment for osteocartilaginous applications. We investigated the influence of synthesis parameters on the physicochemical characteristics of the resulting nanogels and their potential impact on the biocompatibility on all types of human osteocartilaginous cells. Monodisperse nanogels were synthesized with sizes ranging from 268 to 382 nm according to the acidic solution used (i.e., either citric or acetic acid) with overall positive charge surface. Our results demonstrated that purified chitosan-based nanogels neither affected cell proliferation nor induced nitric oxide production in vitro. However, nanogels were moderately genotoxic in a dose-dependent manner but did not significantly induce acute embryotoxicity in zebrafish embryos, up to 100 µg∙mL<sup>−1</sup>. These encouraging results hold great promise for the intra-articular delivery of drugs or diagnostic agents for joint pathologies.
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spelling doaj.art-4d84442f006e47c48bcd84c8255f1ad92023-11-30T21:40:03ZengMDPI AGNanomaterials2079-49912022-04-01128133710.3390/nano12081337Chitosan-Based Nanogels: Synthesis and Toxicity Profile for Drug Delivery to Articular JointsSeng Manivong0Araceli Garcia Ac1Shunmoogum A. Patten2Julio C. Fernandes3Mohamed Benderdour4Xavier Banquy5Florina Moldovan6Valérie Gaëlle Roullin7Centre de Recherche, CHU Sainte-Justine, Montreal, QC H3T 1C5, CanadaFaculté de Pharmacie, Université de Montréal, Montreal, QC H3T 1J4, CanadaInstitut National de la Recherche Scientifique, Centre Armand-Frappier Santé Biotechnologie, Laval, QC H7V 1B7, CanadaCentre de Recherche, Hôpital du Sacré-Cœur de Montréal, Faculté de Médecine, Université de Montréal, Montreal, QC H4J 1C5, CanadaCentre de Recherche, Hôpital du Sacré-Cœur de Montréal, Faculté de Médecine, Université de Montréal, Montreal, QC H4J 1C5, CanadaFaculté de Pharmacie, Université de Montréal, Montreal, QC H3T 1J4, CanadaCentre de Recherche, CHU Sainte-Justine, Montreal, QC H3T 1C5, CanadaFaculté de Pharmacie, Université de Montréal, Montreal, QC H3T 1J4, CanadaOne important challenge in treating avascular-degraded cartilage is the development of new drugs for both pain management and joint preservation. Considerable efforts have been invested in developing nanosystems using biomaterials, such as chitosan, a widely used natural polymer exhibiting numerous advantages, i.e., non-toxic, biocompatible and biodegradable. However, even if chitosan is generally recognized as safe, the safety and biocompatibility of such nanomaterials must be addressed because of potential for greater interactions between nanomaterials and biological systems. Here, we developed chitosan-based nanogels as drug-delivery platforms and established an initial biological risk assessment for osteocartilaginous applications. We investigated the influence of synthesis parameters on the physicochemical characteristics of the resulting nanogels and their potential impact on the biocompatibility on all types of human osteocartilaginous cells. Monodisperse nanogels were synthesized with sizes ranging from 268 to 382 nm according to the acidic solution used (i.e., either citric or acetic acid) with overall positive charge surface. Our results demonstrated that purified chitosan-based nanogels neither affected cell proliferation nor induced nitric oxide production in vitro. However, nanogels were moderately genotoxic in a dose-dependent manner but did not significantly induce acute embryotoxicity in zebrafish embryos, up to 100 µg∙mL<sup>−1</sup>. These encouraging results hold great promise for the intra-articular delivery of drugs or diagnostic agents for joint pathologies.https://www.mdpi.com/2079-4991/12/8/1337nanogelbiopolymerhyaluronic acidosteoarthritisbiocompatibilitycartilage
spellingShingle Seng Manivong
Araceli Garcia Ac
Shunmoogum A. Patten
Julio C. Fernandes
Mohamed Benderdour
Xavier Banquy
Florina Moldovan
Valérie Gaëlle Roullin
Chitosan-Based Nanogels: Synthesis and Toxicity Profile for Drug Delivery to Articular Joints
Nanomaterials
nanogel
biopolymer
hyaluronic acid
osteoarthritis
biocompatibility
cartilage
title Chitosan-Based Nanogels: Synthesis and Toxicity Profile for Drug Delivery to Articular Joints
title_full Chitosan-Based Nanogels: Synthesis and Toxicity Profile for Drug Delivery to Articular Joints
title_fullStr Chitosan-Based Nanogels: Synthesis and Toxicity Profile for Drug Delivery to Articular Joints
title_full_unstemmed Chitosan-Based Nanogels: Synthesis and Toxicity Profile for Drug Delivery to Articular Joints
title_short Chitosan-Based Nanogels: Synthesis and Toxicity Profile for Drug Delivery to Articular Joints
title_sort chitosan based nanogels synthesis and toxicity profile for drug delivery to articular joints
topic nanogel
biopolymer
hyaluronic acid
osteoarthritis
biocompatibility
cartilage
url https://www.mdpi.com/2079-4991/12/8/1337
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AT juliocfernandes chitosanbasednanogelssynthesisandtoxicityprofilefordrugdeliverytoarticularjoints
AT mohamedbenderdour chitosanbasednanogelssynthesisandtoxicityprofilefordrugdeliverytoarticularjoints
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