Cartilage-targeting poly(ethylene glycol) (PEG)-formononetin (FMN) nanodrug for the treatment of osteoarthritis

Abstract

Intra-articular (IA) injection is an efficient treatment for osteoarthritis, which will minimize systemic side effects. However, the joint experiences rapid clearance of therapeutics after intra-articular injection. Delivering system modified through active targeting strategies to facilitate localization within specific joint tissues such as cartilage is hopeful to increase the therapeutic effects. In this study, we designed a nanoscaled amphiphilic and cartilage-targeting polymer-drug delivery system by using formononetin (FMN)-poly(ethylene glycol) (PEG) (denoted as PCFMN), which was prepared by PEGylation of FMN followed by coupling with cartilage-targeting peptide (CollBP). Our results showed that PCFMN was approximately regular spherical with an average diameter about 218 nm. The in vitro test using IL-1β stimulated chondrocytes indicated that PCFMN was biocompatible and upregulated anabolic genes while simultaneously downregulated catabolic genes of the articular cartilage. The therapeutic effects in vivo indicated that PCFMN could effectively attenuate the progression of OA as evidenced by immunohistochemical staining and histological analysis. In addition, PCFMN showed higher intention time in joints and better anti-inflammatory effects than FMN, indicating the efficacy of cartilage targeting nanodrug on OA. This study may provide a reference for clinical OA therapy.

Application of the pH-Responsive PCL/PEG-Nar Nanofiber Membrane in the Treatment of Osteoarthritis

“…The synthesis of PEG-Nar was conducted based on a previous study ( Eivazi et al, 2020 ; Xiong et al, 2021 ). Briefly, 1.0 g mPEG-COOH (Mw = 2000, Macklin, China), 0.5 g naringenin (Nar, J&K Scientific, China), 1.5 g 4-dimethylamino pyridine (DMAP, Sigma-Aldrich, United States), and 3.0 g 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide hydrochloride (EDC, Sigma-Aldrich, United States) were dissolved in 1.0 ml dimethyl sulfoxide (DMSO, Macklin, China) under sonication for 5 min.…”

Bone-Targeted Nanoparticle Drug Delivery System: An Emerging Strategy for Bone-Related Disease

“…Compared with FMN, PEGylation of FMN had higher drug solubility and CollBP increased drug accumulation in the joint site. A variety of inflammation-related factors decreased significantly after treatment, which also ameliorated ACLT-induced cartilage destruction, and ultimately achieved an effective OA retarding effect ( Xiong et al, 2021 ). Xue et al affixed a type II collagen-targeting peptide to a mesoporous polydopamine (MPDA) dual drug delivery system (RB@MPMW) modified with a metal organic backbone (MOF).…”

Knee Osteoarthritis Therapy: Recent Advances in Intra-Articular Drug Delivery Systems

“… [ 160 ] PCFMN/collagen II-binding peptide FMN Cartilage targeting In vitro & vivo Chondrocytes; Rats The in vitro test using IL-1β stimulated chondrocytes indicated that PCFMN was biocompatible and upregulated anabolic genes while simultaneously downregulated catabolic genes of the articular cartilage; PCFMN could effectively delay the progression of osteoarthritis and showed a longer joint placement time and better anti-inflammatory effect than FMN, suggesting that the cartilage targeted nanosheets have a certain therapeutic effect on osteoarthritis. [ 163 ] XG/PSBMA/collagen II-binding peptide - Cartilage targeting; Lubrication In vitro - The nanoparticles possess antioxidation verified by DPPH assay and exhibits synergistically enhanced ROS (OH, O 2 − and H 2 O 2 ) scavenging. [ 165 ] PEG-SWCNTs - Cartilage targeting In vitro & vivo Chondrocytes; Mice PEG-SWCNTs were capable to persist in the joint cavity for a prolonged time, entered the cartilage matrix, and delivered gene inhibitors into chondrocytes of both healthy and OA mice.…”

“…Cartilage targeting is the most popular strategy that can be achieved by modifying the PNPs with cartilage affinity groups. 162 Collagen II-binding peptide-modified formononetin (FMN)-poly (ethylene glycol) (PEG) NPs, 163 , 164 xanthan gum-poly (sulfobetaine methacrylate) (XG-PSBMA) NPs, 165 WYRGRL (a short cartilage-targeting peptide sequence)-modified PLGA NPs, 164 , 166 polyethylene glycol (PEG) chains (PEG-SWCNTs) modified with single-walled carbon nanotube (SWCNT) NPs, 44 and quaternary ammonium cation modified PLGA NPs 167 have been developed for cartilage targeting. In some instances, cartilage targeting originates in the basic material of the PNPs.…”

“…In some instances, cartilage targeting originates in the basic material of the PNPs. 163–166 In addition, dextran sulfate used to target macrophages, 168 HAP-1 peptide used to target synovial, 169 O-HTCC (O-(2-hydroxyl) propyl-3trimethyl ammonium chitosan chloride) and polyphenol–poloxamer used to target ROS, 170 , 171 C11 peptide (the C-terminal region of rh174) used to target bone, 172 PNPs have also been developed to target the specific microenvironment of OA joint.…”