Niacin-Loaded Liquid Crystal Nanoparticles Ameliorate Prostaglandin D2-Mediated Niacin-Induced Flushing and Hepatotoxicity

Abstract

Niacin plays a significant role in the therapy and management of mixed dyslipidemia. Nevertheless, its administration in raw form is contraindicated due to potential adverse effects including hepatotoxicity and cutaneous flushing. Prostaglandin D2 (PGD2) plays a crucial role in the signaling cascade of niacin-induced flushing. To address the potential adverse reactions linked to niacin therapy, we developed a niacin-loaded lyotropic liquid crystal nanoparticle (NLCS) crafted explicitly for the oral administration of niacin. NLCSs were produced by disrupting the cubic gel of glyceryl monostearate (GMS). The nanoparticles demonstrated notable drug-loading capabilities with a size of approximately 255 ± 31.6 nm. Furthermore, NLCS displayed sustained release behavior, indicating their potential for controlled and prolonged drug delivery. Efficient encapsulation and minimal interaction between niacin and other excipients were evidenced through Fourier transform infrared and X-ray diffraction studies, establishing their high stability. In vitro studies suggested that the nanoparticles had good antioxidant activity, swelling behavior, and biocompatibility. Additionally, compared to raw niacin, NLCS showed a higher in vivo therapeutic efficacy, less hepatotoxicity, a more refined lipid profile, and an improved complete blood count (CBC) profile. In addition, it was shown that animals treated with NLCS had lower PGD2 levels than those treated with raw niacin. In conclusion, our study highlights the potential of NLCS as a promising strategy to alleviate the side effects linked to the direct ingestion of pure niacin. These nanoparticles offer a solution to flushing-like symptoms and hepatotoxicity, positioning them as a viable therapeutic option for managing dyslipidemia.