Synthesis and biological study of thiopheneyl/piperazinl-α-aminophosphonate-chitosan conjugates as biologically active carriers for controlled delivery of curcumin.

In this study, a series of novel chitosan-based α-aminophosphonate conjugates (CS-AM-PHs) incorporating thiophene or piperazine moieties were synthesized. Structural characterization using FT-IR, 1H-NMR and TGA analysis confirmed successful conjugation, with grafting degrees of 58-68% and enhanced thermal stability over native CS. Among the synthesized systems, four conjugates (CS-TPP-THP, CS-TEP-THP, CS-TIP-THP, and CS-TEP-PIP) demonstrated effective loading of curcumin (CUR), with CS-TEP-PIP achieving the highest loading efficiency (75.9%). Swelling studies at pH 5.3 and 7.4 indicated pH-responsive behavior, particularly for CS-TEP-PIP, which exhibited significantly higher water uptake, correlating with its faster drug release profile. In vitro CUR release demonstrated sustained and pH-dependent release kinetics over extended periods, with release data fitting zero-order, Higuchi, and Korsmeyer-Peppas models depending on polymer structure and pH. Additionally, the synthesized CS-AM-PH conjugates demonstrated notable antibacterial activity, with thiophene-based derivatives (CS-TPP-THP) exhibiting the strongest inhibition against the tested bacterial strains. For cytocompatibility, in vitro MTT assays were performed on human cancer cell lines (HCT-116, HepG-2, PC-3, MCF-7) and the normal WISH cell line; conjugates displayed variable but selective anticancer activity, with CS-TEP-PIP@CUR exhibiting the most pronounced selectivity for cancerous cell over normal cells. Collectively, the synthesized CS-AM-PH conjugates exhibited improved physicochemical properties, high CUR-loading capacity, and controlled drug-release behavior, highlighting their potential as effective chitosan-based carriers for sustained and targeted anticancer drug delivery. The findings highlight the dual functionality of the developed conjugates as both drug-delivery carriers and promising antimicrobial agents.