Development and preclinical evaluation of diclofenac sodium loaded hydroxyethyl starch nanoformulation for parenteral use

Abstract

Inflammation research is gaining immense interest in mainstream medicine since researchers uncover evidence that inflammation ignites and feeds chronic illness. It is a protective response to begin the healing process by removing harmful stimuli, including damaged cells, irritants, or pathogens. Inflammation occurs in various disease conditions such as arthritis, diabetes, cardiovascular, neurological, cancer and other autoimmune diseases. Progression of the disease condition affects major organs of the body including brain, kidneys, liver, lungs, muscle, bones etc. and hence disease management at early stage is essential. Disease is currently managed mainly via non-steroidal antiinflammatory drugs (NSAIDs) and it is estimated that 30 million people intake NSAIDs worldwide. Diclofenac Sodium is the most commonly prescribed NSAIDs with its name on seventy four national essential medical lists (EMLs). Although this drug has proven its efficacy in the treatment of pain and inflammation, it often presents safety and tolerability issues, including serious concerns related to gastro-intestinal (GI), cardiovascular (CV), and renal toxicity. Toxicity of DS results from the high clinical doses administered and the route of drug delivery adopted. Specifically, GI related toxicity is common when the drug is administered orally since diclofenac is a weak acid. The side effects associated with the oral route can be mitigated by adopting parenteral administration. While intravenous drug delivery helps the drug molecules to reach systemic circulation easily and has excellent therapeutic outcome, it is accompanied by a rapid decline in plasma levels and drug clearance. This is primarily due to the short plasma half-life and protein binding of the drug, thereby demanding multiple injections. In this regard, biopolymeric nanodrug delivery systems can be a good alternative to resolve the limitations of intravenous drug delivery. ...