Intra-articular delivery system of methotrexate for rheumatoid arthritis therapy: An in-suit thermosensitive comprehensive gel of polysaccharide from Aconitum carmichaelii Debx

The polysaccharides (FP) extracted from the lateral roots of Aconitum carmichaelii Debx. (Fuzi) are natural compounds, which have effective therapy for rheumatoid arthritis (RA). Methotrexate (MTX) is the first-line drug for RA, but its application is greatly limited to the toxicity in liver and kidney and drug resistance. In this study, an attempt is made to apply oxidized FP (OFP) as a polymer carrier based on intra-articular delivery system loaded MTX. The FP could be modified and used as comprehensive gel carriers with biocompatibility and degradability for therapy of RA. Firstly, OFP-chitosan-poloxamer 407 in situ gel (OFP-CS-F407-MTX gel) was prepared by natural non-toxic cross-linking agents. Physicochemical characterization was performed by using ¹H NMR and FTIR spectroscopic techniques to assess the successful functionalization of OFP. TGA, SEM and rheological experiment of OFP-CS-F407-MTX gel were investigated. Notably, we loaded MTX into OFP-CS-F407-MTX gel which had remarkable therapeutic efficacy and biosafety for RA. Therefore, OFP-CS-F407-MTX in situ gel delivery system can potentially reduce systemic toxicity and irritation of oral administration of MTX but hold a controlled release of drug for a long period of time.