Atorvastatin Curcumin Conjugate Synthesis Development of Nano Formulation In Silico In Vitro Characterization and Evaluation of Lipid Lowering And Anti Inflammatory Activity

Abstract

Conjugate drugs are evolving into potent techniques in the drug development process for enhancing the biopharmaceutical, physicochemical, and pharmacokinetic properties. Discovering novel therapeutic benefits for current drugs could contribute to new treatment alternatives for individuals with complex medical demands that are safe, inexpensive, and timely. In this consequence drug repurposing is a fascinating scenario. Atorvastatin is the first line of treatment for coronary atherosclerosis and has been recognized for its authoritative anti-inflammatory activity by reducing interleukin (IL-6) levels, tumor necrosis factor alpha (TNF-and#945;) and by inhibiting chemokine receptors on T cells. Statins have anticancer characteristics that suppress proliferation, trigger apoptosis, and decrease metastasis. However its therapeutic efficacy is limited because of its poor solubility and fast pass metabolism. Curcumin an ancient natural compound has no recorded side effects is evidenced in several crucial signaling pathways linked to lipid regulation, inflammation and cancer by condensing TNFstimulated human endothelial cells by interfering with NF-KB. In the current research, the main attention was to overcome solubility related issues of atorvastatin, and curcumin through atorvastatin- curcumin conjugate synthesis and access its synergistic action on atherosclerosis as well as repurposed action on topical inflammation and on colon cancer. To validate distinct activities, various formulations such as nanoparticles and nanocrystals have been developed, and various validation approaches such as in silico, in vitro, and in vivo characterizations were adopted. The new conjugate molecule revealed excellent biopharmaceutical properties. These findings evidenced that nanoparticles and nano crystals of the atorvastatin-curcumin conjugate had a significant and potentially beneficial impact on the treatment and management of atherosclerosis and inflammation respectively. Furthermore, in silico approaches against colon cancer have exhibi