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

Abstract

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−1. These encouraging results hold great promise for the intra-articular delivery of drugs or diagnostic agents for joint pathologies.

Functionalized Nanogels with Endothelin-1 and Bradykinin Receptor Antagonist Peptides Decrease Inflammatory and Cartilage Degradation Markers of Osteoarthritis in a Horse Organoid Model of Cartilage

“…This approach is based on the previously observed effects, such as the synergistic inhibition of endothelin-1 and bradykinin receptors by two peptides, BQ-123 and R-954, respectively, that can decrease pain and prevent the destruction of cartilage in a surgically induced OA model [ 24 ]. CHI- and HA-based nanogels are of interest to improve OA treatments, notably because they could be used as DDS [ 44 , 45 , 46 , 47 ]. In this study, CHI- and HA-based nanogels were developed as a drug delivery platform for the concomitant intra-articular administration of BQ-123 and R-954 peptides.…”

“…Nanogels (NGs) were obtained using an ionic gelation process based on a previously reported protocol [ 47 ]. Briefly, a chitosan solution (CHI, 2.5 mg/mL) in acetic acid (0.5% ( v / v )) and a second solution of sodium tripolyphosphate (TPP, 1.2 mg/mL) (Alfa Aesar, Ward Hill, MA, USA) and 60 kDa sodium hyaluronate (HA, 0.8 mg/mL) were magnetically stirred overnight until complete dissolution.…”

Polymeric Gel Systems Cytotoxicity and Drug Release as Key Features for their Effective Application in Various Fields of Addressed Pharmaceuticals Delivery

“…The effect of chitosan-based nanogels on chondrocytes, synoviocytes, and osteoblasts in patients with osteoarthritis was studied in [ 92 ]. The authors found that the proliferation of these cells exceeds 80% at any concentration of nanogels ( Figure 5 ), and the integrity of the cell membrane is maintained when exposed to nanogels for 72 h.…”

Chitosan-Based Nano-Smart Drug Delivery System in Breast Cancer Therapy

“…Chitosan nanoparticles are formed by the interaction of positively charged chitosan with negatively charged molecules such as DNA, RNA, and drugs, via electrostatic interactions [ 1 , 59 , 84 , 85 , 86 , 87 ]. These nanoparticles can be administered to the body via various routes such as oral, topical, or injection [ 78 , 88 , 89 ].…”