Synthesis, characterization, kinetic release study and evaluation of hydrazone linker in ferrocene conjugates at different pH values
Journal of Drug Delivery Science and Technology
School of Chemical and Metallurgy, University of Witwatersrand, Wits 2050, South Africa; Department of Chemical, Metallurgical and Material Engineering, Tshwane University of Technology, Pretoria, South Africa
Hydrazone linker plays an important role in drug delivery because it is stable under physiological conditions and hydrolytically degradable in mildly acidic environment. In this research, we demonstrated the efficacy of hydrazone linker in polymer-drug conjugation by using it to incorporate an analogue of ferrocene to biodegradable polymers to form conjugates. These conjugates were characterized by NMR, IR and UV spectroscopy. The mass percentage incorporation of the analogue was found to be between 1.95-2.76% from the NMR spectroscopy. The stability of the hydrazone linker of the selected conjugates was evaluated at various pH-values and found to cleave under acidic pH but stable at neutral pH. Various kinetic release models were used to determine the release mechanism of ferrocene analogue from polyaspartamide polymeric carriers. The release profile was found to fit best with Korsmeyer-Peppas model with a diffusion exponent of 1.1.
ferrocene derivative; hydrazone derivative; antineoplastic activity; article; conjugate; drug conjugation; drug delivery system; drug efficacy; drug half life; drug release; drug screening; drug stability; drug synthesis; freeze drying; kidney clearance; melting point; nuclear magnetic resonance; nuclear magnetic resonance spectroscopy; pH; ultraviolet spectroscopy