Newly Synthesized Acetylcholinesterase Inhibitors for Alleviating Alzheimer’s Disease using Solid Lipid Nanoparticles
Rohit Makkar, Paramveer Singh, Chhanda C. Danta, Vandita Kakkar, Indu P. Kaur and Poonam Piplani
Affiliation: University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh-160014, India.
Acetylcholinesterase inhibitors are regarded as the most promising approach to treat Alzheimer’s disease (AD).
However, their anticipated side effects limit their usage. Present investigations involved the incorporation of the newly
synthesized 2-naphthol derivatives (PP-81 and PP-84) into solid lipid nanoparticles (SLNs) to improve their accessibility
to the brain and enhance the levels of acetylcholine. Drug loaded SLNs of PP-81 and PP-84 showed that average particle
size of 138 nm and 186 nm, positive zeta potential and total drug content of 86.13 ± 0.49 % w/v and 81.18 ± 0.78 % w/v
respectively were obtained using microemulsification technique. The particles were found to be spherical in shape, with
high drug entrapment (91.28 ± 0.14 % w/w, PP-81 and 70.94 ± 0.59 % w/w, PP-84) at 10 % drug loading. Confirmation
of SLNs formation was performed using DSC and PXRD studies. In in vitro release study diffusion phenomenon was
predominant and was prolonged up to 24 h. Elevated plus maze test was carried out to evaluate memory acquisition and
retention; post treatment with SLNs and respective free drugs in scopolamine induced spatial memory deficit in mice.
Results indicated a significant increase (p < 0.05) in percentage retention of memory and learning with PP-81 and PP- 84
SLNs respectively at 20 mg/kg. It can be an optimized potential therapeutic and brain targeting approach for the treatment
Keywords: Alzheimer’s disease, acetylcholinesterase inhibitors, microemulsification method, solid lipid nanoparticles, DSC,
PXRD, elevated plus maze.
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