Abstract
Osteoarthritis (OA) is the most common form of joint disease and a leading cause of physical disability, there is an urgent need to attenuate the progression of OA. Intra-articular (IA) injection is an effective treatment for joints diseases, however, the therapeutic effects mostly depend on the efficacy of drug duration in joints. Drug delivery system can provide drug-controlled release and reduce the number of IA injection. In this study, amphiphilic polyurethanes with pendant amino group were synthesized and amide bonds were formed between the amine group of polyurethane and the carboxyl group of kartogenin (KGN), a small molecular reported to show both regenerative and protective effects on cartilage. Our results showed that KGN-conjugated polyurethane nanoparticles (PN-KGN) were spherical and regular in shape with an average size of 25 nm and could sustained and controlled release of KGN in vitro. PN-KGN showed no cytotoxicity and pro-inflammatory effects on chondrocytes. The therapeutic effects in OA model showed that IA injection of KGN could attenuate the progress of OA, however, the cartilage degeneration became obviously at 12 weeks with matrix loss and vertical fissures. By contrast, IA injection of PN-KGN showed less cartilage degeneration with significant lower OARSI scores even at 12 weeks, indicating PN-KGN could further arrest the development of OA. Immunohistochemistry also validated that IA injection of PN-KGN retained the normal compositions of cartilage matrix, with much stronger Col II staining and less Col I staining. In conclusion, IA injection of PN-KGN is a better potential strategy to treat OA, with long-time cartilage protection and less IA injections.
Highlights
Osteoarthritis (OA) is the most common form of chronic joint disease affecting 250 million people worldwide and anticipated to be the fourth leading cause of physical disability by the year 2020 with increasing aging population (Woolf & Pfleger, 2003; Loeser et al, 2016)
The polymers were synthesized from poly-(ethylene glycol) (PEG), hexamethylene diisocyanate (HDI) and N-BOC-Serinol with molar ratio of 1:2:1, followed by the further deprotection process of BOC-protected amino groups, which was performed as previously described method (Fang et al, 2014)
Successful conjugation of polyurethane nanoparticles (PN)-KGN was confirmed by Fourier transform infrared spectroscopy (FTIR) and 1H NMR
Summary
Osteoarthritis (OA) is the most common form of chronic joint disease affecting 250 million people worldwide and anticipated to be the fourth leading cause of physical disability by the year 2020 with increasing aging population (Woolf & Pfleger, 2003; Loeser et al, 2016). It is characterized by progressive degeneration of cartilage and subchondral bone changes. Xu et al (2015) reported that intra-articular (IA) injection of KGN promoted cartilage repair and increased hyaline-like cartilage formation in New Zealand white rabbits with full-thickness cartilage defects in the femur. Reducing the frequency of joint injection and prolonging the efficacy of KGN can be beneficial to clinical application
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