Synthesis, Characterization and Kinetic Release Profile of Iron Containing Polymeric Co-conjugates with Antiproliferative Activity B. D. Nkazi • E. W. Neuse • E. R. Sadiku • B. A. Aderibigbe Received: 16 May 2013 / Accepted: 9 September 2013 / Published online: 21 September 2013 Ó Springer Science+Business Media New York 2013 Abstract In this research, the incorporation of ferrocen- ecarboxyaldehyde, 3-ferrocenylprop-2-enal and acetylfer- rocene to a polymeric backbone via hydrazone bond to form conjugates and co-conjugates was demonstrated. The conjugates and co-conjugates containing bioactive agents were characterized by nuclear magnetic resonance spec- troscopy, Fourier transform spectroscopy and UV–visible Spectroscopy. Kinetic release studies of 3-ferrocenylprop- 2-enal and acetylferrocene from the polymeric carriers was performed using various mathematical release models. The mechanism of release of ferrocenylpropenal and acetyl- ferrocene followed Korsmeyer-Peppas release profile with a diffusion coefficient of n [ 5 at selected pH values indicating anomalous (non-Fickian) diffusion. Keywords Ferrocene  Polymer-drug conjugation  Hydrazone bond  Co-conjugates  Combination chemotherapy 1 Introduction Recently, there has been an increase in the study of fer- rocene compounds and this is because of their lipophilicity, reversible redox chemistry and stability in biological media [1–9]. Several studies have reported the antiproliferative activity of ferrocene compounds against several human tumor cell lines and ascitic murine tumors [10, 11]. In our research group, an article was published on the cytotoxic activity of macromolecular ferrocene conjugates against Colo 320 DM human colon cancer line [12]. In another study, ferrocene compound was found to induce in vitro and in vivo activation of mouse lymphocytes and macro- phages; it also showed an antitumor effect in mice, due to its immune-stimulatory property [13]. Polymer-drug conjugation is the application of macro- molecular carriers that consists of water-solubilizing groups, functional groups for reversible drug anchoring and a homing device that directs the conjugate molecule selectively to the target tissue [14]. The choice of func- tional group for drug incorporation is very important because the cleavage of drug from the polymer backbone is either by enzymatic or hydrolysis. Selected functional groups can prolong drug release, thereby improving the drug bioavailability [15, 16]. Presently, there are several drug delivery systems, such as: nanoparticles, lipsosomes, hydrogels, microcapsules, matrices etc. In all these sys- tems, the drugs are incorporated into the systems without the formation of covalent bonds or merely dispersed. In polymer drug conjugation, which is extensively reviewed by Duncan [17], Satchi-Fainaro et al. [18], Vicent and Duncan [19], the drug is covalently bonded to the poly- meric backbone. The technique of polymer drug conjuga- tion offers the possibility of covalently attaching a cocktail of drugs to a single polymeric carrier for combined chemotherapy. Combination chemotherapy has been found to be the best approach to combat drug resistance by combining two or three chemotherapeutic agents. It has been found to decrease tumor resistant to treatment, reduce drug toxicity by using drugs at lower doses and it addresses several B. D. Nkazi  E. W. Neuse School of Chemical and Metallurgical Engineering, University of Witwatersrand, Wits, Johannesburg 2050, South Africa E. R. Sadiku  B. A. Aderibigbe (&) Department of Chemical, Metallurgical and Material Engineering (Polymer Technology Division), Tshwane University of Technology, Pretoria, South Africa e-mail: blessingaderibigbe@gmail.com 123 J Inorg Organomet Polym (2014) 24:302–314 DOI 10.1007/s10904-013-9968-9