Design and evaluation of Poly(δ-decalactone) based nanoemulsions for mitigating Lumiracoxib-associated hepatotoxicity

Lumiracoxib (LXB) was in use for the treatment of rheumatoid arthritis and osteoarthritis but was withdrawn from the market due to severe hepatotoxicity. Nevertheless, nanotechnology-based reformulation of such drug can tailor pharmacokinetics through controlled release and reduced off-target liver accumulation, improving efficacy and safety. Thus, the present study explored the potential of poly(δ-decalactone) (PDL)-based nanoemulsion (NE) to reduce the hepatic toxicity of LXB. Tailor-made diblock (mPEG-b-PDL) and triblock (PDL-b-PEG-b-PDL) co-polymers were used as surfactants, while homopolymers (B-PDL, B-PJL-COOH and B-PJL-OH) were used as polymeric oil to fabricate NEs. NEs prepared using B-PDL (F3 and F4) enhanced the aqueous solubility of LXB by 30.4 ± 5.4 and 37.3 ± 4.8-fold, respectively. In vitro cytotoxicity results revealed that prepared NEs reduced the cytotoxicity of LXB in liver cancer (HepG2) cells by approx. 2-fold. Furthermore, liver toxicity and inflammatory markers were evaluated using Multiplex® after LXB NE treatment and results showed that NEs performed better compared to free LXB. Evaluation in an in vivo arthritic model further demonstrated NEs capability in reducing LXB-induced hepatic toxicity with improved anti-inflammatory activity. These findings suggest that PDL NEs may offer a promising strategy for improving the biopharmaceutical performance and safety profile of LXB.