Folate receptor-targeted mixed polysialic acid micelles for combating rheumatoid arthritis: in vitro and in vivo evaluation

AbstractObjective: Rheumatoid arthritis (RA) is associated with chronic inflammation. The suppression of inflammation is key to the treatment of RA. Glucocorticoids (GCs) are classical anti-inflammatory drugs with several disadvantages such as poor water solubility and low specificity in the body. These disadvantages are the reasons for the quick elimination and side effects of GCs in vivo. Micelles are ideal carriers for GCs delivery to inflamed synovium. We set out to improve the targeting and pharmacokinetic profiles of GCs by preparing a targeting micelle system.Methods: In this study, natural chlosterol (CC) and folic acid (FA) were used to fabricate polysialic acid (PSA) micelles for the targeted delivery of Dexamethasone (Dex). The biodistribution and therapeutic efficacy of the resulting micelles were evaluated in vitro and in vivo.Results: PSA-CC and FA-PSA-CC micelles showed a size below 100 nm and a moderate negative charge. PSA-CC and FA-PSA-CC micelles could also enhance the intracellular upt...