Synthesis and characterization of novel polymer-drug conjugate based on the anhydride containing copolymer as a potential method for drug carrier


JOURNAL OF MACROMOLECULAR SCIENCE PART A-PURE AND APPLIED CHEMISTRY, vol.55, no.2, pp.192-204, 2018 (SCI-Expanded) identifier identifier


5-Fluorouracil (5FU) is in clinical use as an antitumor agent for the treatment of several types of solid tumors and cancers. However, development of drug resistance within the tumor cells and side effects has been a major limitation for the clinical use of 5FU. Preparation polymer-5FU conjugation is a promising potential antitumor drug and alternative pathway that could be used to treatment of cancer. For this purpose, water soluble poly(maleic anhydride-alt-N-vinyl pyrrolidone)[Poly(MA-alt-NVP)] is synthesized via charge transfer complex (CTC) copolymerization with benzoyl peroxide as an initiator at 80 degrees C under nitrogen atmosphere. CTC mechanism is formed between through MA and NVP by determined using Uv-vis spectroscopy. Molar absorption coefficient (epsilon(AD)) and equilibrium constant (K-AD) of the complex are determined by Scott equation. The results obtained from indicate that copolymerization of MA: NVP system is preceded via alternating mechanism. The compositions of synthesized copolymers are also investigated by elemental analysis and the reactivity ratios of these monomers are calculated by using the elemental analysis data through Kelen-Tudos, Mayo-Lewis, Fineman-Ross and Inverted Fineman-Ross equations. For preparation of polymer-drug conjugate, chemical modification is employed between the copolymer and 5FU. Polymer-drug conjugate and conjugation mechanism are enlightened by ATR-FTIR, NMR, HR-Raman and XRD methods.