Polymer drug conjugates containing memantine, tacrine and cinnamic acid: promising nanotherapeutics for the treatment of Alzheimer’s disease

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.