Repositioning Bevacizumab: A Promising Therapeutic Strategy for Cartilage Regeneration

Abstract

Drug discovery and development has been garnering an increasing trend of research due to the growing incidence of the diverse types of diseases. Recently, drug repositioning, also known as drug repurposing, has been emerging parallel to cancer and tissue engineering studies. Drug repositioning involves the application of currently approved or even abandoned drugs as alternative treatments to other diseases or as biomaterials in other fields including cell therapy and tissue engineering. In this review, the advancement of the antiangiogenesis drugs that were used as treatment for cancer and other diseases, with particular focus on bevacizumab, will be described. This will include an overview of the nature and progression of osteoarthritis (OA), one of the leading global degenerative diseases that cause morbidity, and the development of its therapeutic strategies. In addition, this will also feature the nonsteroidal anti-inflammatory drugs that are commonly prescribed for OA and the benefits of repositioning bevacizumab as alternative treatments for other diseases and as biomaterials for cartilage regeneration. To date, a few number of studies, employing different modes of administration and varying dosages in diverse animal models, have shown that bevacizumab can be used as a signal and can promote both in vitro and in vivo cartilage regeneration. However, other antiangiogenesis drugs and their effects in chondrogenesis and cartilage regeneration are also worth investigating.

Bevacizumab tested for treatment of knee osteoarthritis via inhibition of synovial vascular hyperplasia in rabbits

“…These results demonstrate that bevacizumab inhibits VEGF expression and exerts a certain effect on the treatment of OA. This finding is consistent with Nagai [10] and Soojung Lee [11].…”

“…Lee et al. [11] reported significant cartilage regeneration via the injection of 2 mg/kg of bevacizumab into the articular cavity in a rabbit OA model. The dose of bevacizumab in the vitreous cavity was 1–1.25 mg in animal experiments, and some toxic effect appeared at doses higher than 5.0 mg [12], [13].…”

Sustained delivery of anti-VEGF from injectable hydrogel systems provides a prolonged decrease of endothelial cell proliferation and angiogenesisin vitro

“…9,10 Bevacizumab is also being examined for other clinical applications, including various cancers, 8 age-related macular degeneration, 11,12 and to induce cartilage regeneration. 13 Glioblastoma patients that are administered bevacizumab via intravenous injection following tumour resection show improved progression-free survival (PFS) and quality of life, however no improvement in overall survival (OS) time has been shown. 14,15 The limited efficacy of intravenous bevacizumab treatment for glioblastoma is due, in part, to the blood brain barrier (BBB) which prevents passage of large molecules from the blood stream to the brain tissue and thus to the tumour site.…”

Monitoring the Response of Hyperbilirubinemia in the Mouse Brain by In Vivo Bioluminescence Imaging

“…Bevacizumab (Avastin) is a recombinant, anti-human vascular endothelial growth factor (VEGF), monoclonal antibody currently used in molecular-targeted therapies for some types of cancers [ 48 ]. Recently repositioning of bevacizumab has been proposed for cartilage regeneration [ 49 ]. We have observed that BBB stabilization by administration of bevacizumab [ 36 ] reduces bioluminescence output in the brain area of the MITO-Luc mouse model undergone to induce hyperbilirubinemia.…”