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

Abstract

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
• polymer-drug conjugate
• memantine
• tacrine
• polyamidoamine
• cinnamic acid

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The financial assistance of the Govan Mbeki Research and Development Council, University of Fort Hare, Medical Research Council, and National Research Foundation, South Africa, towards this research are hereby acknowledged. The views and opinions expressed in this manuscript are those of the authors and not of MRC or NRF. This work was supported by South African National Research Foundation; South African Medical Research Council.