Molecular Insights of Hyaluronic Acid as Potential Source of Polymer-Drug Conjugate in the Target-Mediated Treatment of Cancer

摘要

The naturally occurring polysaccharide hyaluronic acid (HA) is a major component of the extracellular matrix and is found over expressed in many cancer cells. Hyaluronic acid is reported to be a potential carrier for drug delivery with the dual advantage of accumulation at the tumor site and receptor-mediated uptake. The use of drugs conjugated with macromolecules was shown to improve the drug pharmacokinetic profile. The various biological potentials such as biodegradability, biocompatibility, non-toxicity, hydrophilicity and non-immunogenicity, together with the availability of various chemical groups that allow the conjugation of drugs, put forward HA as a potential choice for the development of drug conjugates. In this context, the present study is focused to provide, through docking studies, insights on the activity of cancer drugs such as methotrexate, 3',5'-dichloromethotrexate and ornithine-methotrexate and their activity against the receptor caspase-1, which is a well-established drug target in the treatment of cancer. The docking study envisages that the usage of methotrexate properly conjugated to the natural polysaccharide HA might serve as a potential drug to effectively treat some cancer diseases.