Thermo‐Sensitive Dual‐Functional Nanospheres with Enhanced Lubrication and Drug Delivery for the Treatment of Osteoarthritis

Abstract

Osteoarthritis is a typical degenerative joint disease related to a lubrication deficiency of articular cartilage, which is characterized by increased friction at the joint surface and severe inflammation of the joint capsule. Consequently, therapies combining lubrication restoration and drug intervention are regarded as a promising strategy for the treatment of osteoarthritis. In the present study, thermo‐sensitive dual‐functional nanospheres, poly[N‐isopropylacrylamide‐2‐methacryloyloxyethyl phosphorylcholine] (PNIPAM‐PMPC), are developed through emulsion polymerization. The PNIPAM‐PMPC nanospheres could enhance lubrication based on the hydration lubrication mechanism by forming a tenacious hydration layer surrounding the zwitterionic headgroups, and achieve local drug delivery by encapsulating the anti‐inflammatory drug diclofenac sodium. The lubrication and drug release tests showed improved lubrication and thermo‐sensitive drug release of the nanospheres. The in vitro test using cytokines‐treated chondrocytes indicated that the PNIPAM‐PMPC nanospheres were biocompatible and upregulated anabolic genes and simultaneously downregulated catabolic genes of the articular cartilage. In summary, the developed PNIPAM‐PMPC nanospheres, with the property of enhanced lubrication and local drug delivery, can be an effective nanomedicine for the treatment of osteoarthritis.

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

“…In addition, in vitro experiments further showed that PNIPAM-PMPC nanospheres were biocompatible and protected chondrocytes from cytokine-induced degeneration. [ 157 ] HA/pNiPAM - Thermo-Sensitive; Slow release In vitro & vivo Human synovial fibroblasts; Mice Nanoparticles were biocompatible, providing a longer residence time at the injection site, protecting cartilage, reducing pro-inflammatory cytokines and maintaining callus thickness. [ 158 ] Chitosan oligosaccharide/ pluronic F127 KGN/Diclofenac sodium Thermo-Sensitive/Slow release In vitro & vivo Chondrocytes; Macrophage-like cells; BMSCs In order to achieve dual drug release, KGN was covalently cross-linked to the outer layer of the nanospheres, while DCF was loaded into the core of the nanospheres, showing the immediate release of DCF and the continuous release of KGN, which were independently controlled by temperature changes; The hypothermic nanospheres effectively inhibited the inflammation of chondrocytes and macrophage-like cells induced by endotoxin and induced mesenchymal stem cells to differentiate into cartilage.…”

“…Microenvironmental-sensitive drug-release strategies have been attractive for PNP drug delivery. pH and temperature sensitive PNPs are rapidly evolving, including hollow dextran/poly (N-isopropyl acrylamide) NPs, 156 dual-functional poly[N-isopropylacrylamide-2-methacryloyloxyethyl phosphorylcholine] (PNIPAM-PMPC) nanospheres, 157 hyaluronic acid-poly(N-isopropylacrylamide) (HA-pNiPAM) nanospheres, 158 and chitosan oligosaccharide-conjugated pluronic F127 grafting carboxyl group nanospheres 159 which possess temperature-responsive release properties. Previous studies showed that NH 4 HCO 3 laden poly (lactic-co-glycolic acid) (PLGA) NPs demonstrate pH-responsive drug release.…”

Charge‐Guided Micro/Nano‐Hydrogel Microsphere for Penetrating Cartilage Matrix

“…Through surface modification, the hydrogel microspheres could play a bearing lubrication role in the joint cavity. Zhang et al [26] loaded the drug within hydrogel microspheres, which both prematurely prevented the drug from being removed and controlled its release. The appropriate size of hydrogel microspheres enables them to avoid being cleared by the blood or lymphatic vessels to the greatest extent, resulting in a prolonged half-life.…”

Injectable Multifunctional Drug Delivery System for Hard Tissue Regeneration under Inflammatory Microenvironments

“…To overcome these limitations, the development of drug delivery systems has been considered crucial to modulate the desired cell phenomenon adjusted to the intended use. − Among available systems, halloysite clay nanotubes (HNTs) have been proven to be an adequate platform to promote sustained drug delivery in association with GelMA. , HNTs are naturally formed by the exfoliation process of aluminosilicate minerals (Al 2 Si 2 O 5 (OH) 4 · n H 2 O). This process results in a bilayered hollow tubular structure with a positively charged inner surface afforded by alumina composition (Al–OH) and a negatively charged external surface consisting of silicon dioxide (SiO 2 ).…”