Sustained Intra-Articular Delivery of Infliximab Biosimilar Using Biodegradable Polymeric Microspheres

The introduction of the biological drugs, in particular, the monoclonal antibody and fusion protein, against tumor necrosis factor (TNF) and other biologics into the real-life clinical practice have substantially improved the outcome of several autoimmune inflammatory disorders, such as ankylosing spondylitis (AS), psoriatic arthritis (PsA), rheumatoid arthritis (RA), Osteoarthritis (OA) and uveitis. However, the dosing regimen of Infliximab and other anti-TNF antibodies requires monthly intra-articular injections followed by regular intra-articular injections at 4–16-week intervals. In 2021, the FDA approved an innovative port delivery system of that can be implanted intra-articularly to slowly release the active ingredient anti-TNF antibody and reduce injection frequency to once every 6 months. An approach utilizing polymeric slow-release microspheres encapsulating a full-length antibody, such as Infliximab, would be much more patient-friendly because it could be injected intra-articularly, avoiding surgical implantation. While microsphere encapsulation is traditionally successful for small molecule hydrophobic drugs, we assessed two different polymers, namely poly(D, L-lactide-co-glycolide) (PLGA) and poly(epsilon-caprolactone) (PCL) and discovered the benefits of utilizing a slow degrading hydrophobic polymer such as PCL for large protein therapeutic. Using the traditional double emulsion fabrication method with PCL polymer, we could produce microspheres that encapsulate Infliximab antibody and demonstrate the release of biologically active therapeutic agent for up to 60 days. This novel approach could lead to significant advancements in our field and potentially open new avenues for future research.