Pharmaceutical potential of tacrolimus-loaded albumin nanoparticles having targetability to rheumatoid arthritis tissues.

Albumin is considered an attractive dug carrier for hydrophobic drugs to target inflamed joints of rheumatoid arthritis. This study focused on the pharmaceutical potential of albumin-based nanoparticles (NPs) on delivery of tacrolimus (TAC) to enhance targetability and anti-arthritic efficacy. TAC-loaded human serum albumin (HSA) nanoparticles (TAC HSA-NPs) were prepared using the nab™ technology. The resulting NPs were 185.8 ± 6.8 nm in diameter and had a zeta potential value of -30.5 ± 1.1 mV, as determined by dynamic light scattering. Particles were uniformly spherical in shape as determined by transmission electron microscopy. The encapsulation efficacy of TAC was 79.3 ± 3.7% and the water solubility was over 46 times greater than that of free TAC. TAC was gradually released from NPs over 24h, which is sufficient time for targeting and treatment of the NPs in inflamed arthritis via intravenous injection. In vitro study using splenocytes excised from spleens of mice following induction of arthritis using collagen clearly demonstrated the anti-proliferative activity of TAC HSA-NPs on activated T cells compared with non-activated T cells. Furthermore, TAC HSA-NPs displayed significantly more anti-arthritic activity than TAC formulations including intravenously administered TAC solution or oral TAC suspension, as reflected by the incidence of arthritis and clinical score (1.6 vs. 3.2 and 5.0, respectively). These improvements were due to the targetability of HSA that facilitated the accumulation of TAC HSA-NPs at inflamed arthritis sites. TAC HSA-NPs are a promising drug delivery system to enhance water solubility and increase accumulation in joints for treatment of rheumatoid arthritis.