Thiolated pectin–doxorubicin conjugates: Synthesis, characterization and anticancer activity studies

© 2017 Elsevier Ltd In this paper, pectin was cross-linked by a coupling reaction with either thioglycolic acid or cystamine dihydrochloride to form thiolated pectins. The thiolated pectins were then coupled with doxorubicin (DOX) derivative to obtain thiolated pectin–DOX conjugates by two different methods, disulfide bond formation and disulfide bond exchange. The disulfide bond exchange method provided a simple, fast, and efficient approach for synthesis of thiolated pectin–DOX conjugates, compared to the disulfide bond formation. Characteristics, physicochemical properties, and morphology of thiolated pectins and thiolated pectin–DOX conjugates were determined. DOX content in thiolated pectin–DOX conjugates using low methoxy pectin was found to be higher than that using high methoxy pectin. The in vitro anticancer activity of thiolated pectin–DOX conjugates was significantly higher than that of free DOX, in mouse colon carcinoma and human bone osteosarcoma cells, but insignificantly different from that of free DOX, in human prostate cancer cells. Due to their promising anticancer activity in mouse colon carcinoma cells, the thiolated pectin–DOX conjugates might be suitable for building drug platform for colorectal cancer-targeted delivery of DOX

Effect of Drug Loading Method on Drug Content and Drug Release from Calcium Pectinate Gel Beads

Drug-loaded calcium pectinate gel (CaPG) beads were prepared by either mixing, absorption, or swelling method. The effects of drug loading method as well as the drug loading factors (i.e., drug concentration, soaking time in drug solution, type of solvent) on drug content and drug release were investigated. The amount of drug uptake (i.e., drug content) into CaPG beads increased as the initial drug concentration increased and varied depending on the loading method. The in vitro release studies in 0.1 N hydrochloric acid (HCl) and pH 6.8 buffer indicated that the drug loading method affected drug release and release parameter, time for 50% of drug release (T50). The mixing method provided a faster drug release and lower T50 than the absorption method and swelling method, respectively. This is probably due to higher drug content in CaPG beads. The increased concentration of drug in soaking solution and soaking time resulted in higher drug content and thus faster drug release (lower in T50 values). When using 0.1 N HCl as solvent for soaking instead of water, the drug release was slower owing to the increase in molecular tortuosity of CaPG beads. The drug release was also affected by pH of the release medium in which drug release in 0.1 N HCl was faster than in pH 6.8 buffer