Topical formulation of a novel drug for the treatment of gouty arthritis

The main objective of this work is to provide a topical formulation of a novel thiocolchicoside derivative drug to treat gout inflammation. The drug has been tested in cell-based assays and showed promising effects but it has not yet been formulated for clinical applications, hence there is a great need to find a delivery method that maximizes the therapeutic effect and minimizes detrimental side effects. The latter aspect is of importance due to general toxicity of the compound in question. Gout is one of the most common and painful inflammatory diseases that can affect human beings. In the last two decades, the incidence of gout among adults (age ≥ 18 years) doubled. According to Elfishawi et al. in the 1989–1992 time period the incidence was 66.6/100,000, whereas it was 136.7/100,000 in the 2009–2010 time period [1]. Gout attacks occur after the precipitation of sodium urate crystals in joints and they are often associated with hyperuricemia. The use of Colchicine in treating gout attacks is known to be effective in most cases, but it is often the therapeutic of last resort, because of the potentially serious and sometimes unbearable side effects that can occur. Colchicine is commonly used as a chemotherapeutic agent or as an anti-inflammatory agent but it often triggers strong side effects, especially on patients suffering from co-morbidities. In previous studies, the basic structure of colchicine was computationally designed by adding different groups such as alkanes, alkenes, esters, ethers, aromatics in different positions In this way, many derivatives were generated and each one of them was characterized by different affinities in the bond between the drug and its protein target, which is tubulin. The thiocolchicoside derivative used in this work, the CCI-001, was initially designed for bladder cancer chemotherapy but modelling and in vitro assays results show CCI-001 as a potential candidate to treat gout due to its efficacy and reduced side effects.The CCI-001 compound has been approved for clinical trials for bladder cancer but it can also be repurposed as an effective therapeutic agent for gout provided it can be properly formulation as a topical medication. Topical delivery rather than enteral or parental routes was chosen for several reasons that are explained below. A very simple protocol containing reagents and conditions of reactions to formulate an inexpensive and simple gel was prepared and, then, the formulation was implemented in the laboratory. Once the formulation was generated, a very thorough characterization has been carried out on the final product to evaluate pH, viscosity, and stability.