The present study was aimed at delivering a low bioavailability drug, rivastigmine hydrogen tartrate (RTG), to the brain through its encapsulation in mesoporous silica nanoparticles (MSNs) and targeted to amyloid inhibition in the brain. MSNs were characterized for size, zeta potential, and drug entrapment using SEM, TEM, HR-TEM, FT-IR, and PXRD. Drug-loaded MSNs were assessed for in vitro release kinetics and ex vivo followed by animal studies. The average size of the prepared blank (MCM-41B) and drug-loaded MSNs (MCM-41L) was 114 ± 2.0 and 145 ± 0.4 nm with the zeta potential of approximately −43.5 ± 1.1 and −37.6 ± 1.4 mV, respectively. MCM-41L exhibited an average entrapment efficiency of 88%. In vitro release studies exhibited early surge followed by a sluggish persistent or constant release (biphasic pattern). Hemolytic studies proved that the developed MCM-41L NPs are less hemolytic compared to RTG. A reduced ThT fluorescence was observed with MCM-41L compared to MCM-41B and RTG in the amyloid inhibition studies. A significant (p < 0.05) inhibition of AChE (acetycholinesterase) was observed for MCM-41L (80 ± 4.98%), RTG (62 ± 3.25%), and MCM-41B (54 ± 4.25%). In vivo pharmacokinetics in Wistar rats revealed that the AUC and mean residence time (MRT) for MCM-41L was sustained and significantly higher (p < 0.05) (780 ± 3.30 ng/L; 5.49 ± 0.25 h) compared to RTG solution (430 ± 3.50 ng/L; 0.768 ± 0.17 h). Similarly, the half-life was found to be significantly higher in case of MCM-41L. The promising result was brain delivery of RTG in Wistar rats which was enhanced almost 127 folds in vivo, using MCM-41L nanoparticles. MCM-41L nanoparticles effectively enhanced the bioavailability of RTG. Conclusively, these can be used for the administration of RTG and other related low bioavailability drugs for improved brain delivery.
Pawan K Pandey, Ashok K Sharma, Sarita Rani, Gaurav Mishra, Dr. Gopal K., Ajit K Patra, Monika Rana, Anuj K Sharma, Awesh K Yadav, and Umesh Gupta, “MCM-41 Nanoparticles for Brain Delivery: Better Choline-Esterase and Amyloid Formation Inhibition with Improved Kinetics”, ACS Biomaterials Science & Engineering, vol. 4, pp. 2860–2869, 2018.