Fibrinogen-based Drug Delivery As A Novel Therapeutic Approach For Leukemia And Rheumatoid Arthritis | 37441
Clinical Pharmacology & Biopharmaceutics
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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.
Mohamed Salah Omar has completed his PhD from Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland. He is currently an Assistant Professor of Biochemistry in the College of Clinical Pharmacy, Taif University, KSA. He has three patents, one is US, one is European and the third is Polish. He has published more than 11 papers in reputed journals.