Aim: To prepare polymer-drug conjugates containing a combination of memantine, tacrine, and E)-N-(3-aminopropyl)cinnamide, promising therapeutics for the treatment of neurodegenerative disorders.
Methods: The conjugates were characterised by 1HNMR, particle size analysis, SEM, LC-MS, TEM/EDX, and XRD, followed by in vitro anti-acetylcholinesterase and drug release studies.
Results: 1H NMR analysis revealed successful drug conjugation with drug mass percentages in the range of 1.3-6.0% w/w. The drug release from the conjugates was sustained for 10 h in the range of 20-36%. The conjugates' capability to inhibit acetylcholinesterase (AChE) activity was significant with IC50 values in the range of 13-44.4 µm which was more effective than tacrine (IC50 =1698.8 µm). The docking studies further confirmed that the conjugation of the drugs into the polymer improved their anti-acetylcholinesterase activity.
Conclusion: The drug release profile, particle sizes, and in vitro studies revealed that the conjugates are promising therapeutics for treating neurodegenerative disorders.
Keywords: Alzheimer’s disease; cinnamic acid; memantine; polyamidoamine; polymer-drug conjugate; tacrine.