Design, synthesis and structural characterization of carrier platforms for therapeutics delivery

Abstract

The dissertation is written in a cumulative format and comprises three previously published, peer-reviewed research articles. Paper I presents an enzymatic approach for the conjugation of recombinant human erythropoietin (rHuEPO) with a semisynthetic hydroxyethyl starch (HES) derivative using a thermoresistant microbial transglutaminase (mTGase) variant, TG16. Amine-functionalized HES (HES-g-NH₂) and its dye-labeled analogue (HES-g-NH₂-R) were synthesized and used as substrates for TG16-catalyzed conjugation with rHuEPO. HES was further utilized for the synthesis of highly hydrophobized stearic acid–HES conjugates (St-HES), which were subsequently investigated as self-assembled carriers for drug delivery, as presented in Paper II. Paper III presents a lipid-based drug conjugate as an alternative to polymer-based delivery systems. Using a dimerization approach, a dimeric artesunate–glycerol monocaprylate conjugate (D-AS-GC) was synthesized, and a nanoemulsion preconcentrate was designed as a substitute carrier for the delivery of the antimalarial drug artesunate.