Mohamed Salah Omar
Taif university, Saudi Arabia
Title: Fibrinogen-Based Drug Delivery as a Novel Therapeutic Approach for Leukemia and Rheumatoid Arthritis
Biography
Biography: Mohamed Salah Omar
Abstract
One of the means to improve therapeutic activity of drugs is their conjugation with biological or synthetic macromolecular carriers. The idea of the carrier is to provide selectivity to the system. Past reports described synthesis, chemical and anti-tumour assays of Methotrexate (MTX) conjugates, but high selectivity was spoiled by toxicity. We developed a new method of coupling MTX with carriers (US 8,623,998 B2): MTX was transformed into its anhydride by treatment with dicyclohexyl carbodiimide. Then, MTX anhydride was coupled to native and glycated fibrinogen in aqueous solution at room temperature. At these conditions, only one of the two carboxylic groups could be acylated, thus chemical cross-linking was avoided. The obtained conjugates were characterized by reasonable uniformity, high purity, lower hydrophobicity and lack of cross-linked fractions as compared to those obtained without control of the reactivity of dicarboxylic functionality of MTX. These effects together reduced the non-specific interactions with hydrophobic components of tissues and thus emphasized the selectivity of the carrier. Native and glycated fibrinogen-MTX conjugates were a prospective way for new anti-cancer drug development due to their high anti-tumor activity. Moreover, their anti-arthritic activity was significantly more effective in suppression of the onset of arthritis in a mouse model than was free MTX. In conclusion, a correct selection of the drug and carrier as well as the type of chemical modification is important. The conditions of modification reaction should allow retention of biological activities of both the drug and the carrier. Native and glycated fibrinogen appear to be a suitable carrier in leukemia and RA.