Inorganic clay nanocomposite system for improved cholinesterase inhibition and brain pharmacokinetics of donepezil (vol 46, pg 8, 2020)

Objective: Brain drug delivery for effective treatment of neurodegenerative disorders is limited due to the selective permeability of blood brain barrier (BBB). During the past few years, development of novel delivery system has attracted considerable attention of formulation scientists to overcome the permeability limitation caused by BBB. Methods: In the present study, laponite (LAP) nanocomposites were exploited for the improved brain delivery of donepezil (DZ) following encapsulation approach due to their nano-size and positive charge at pH Result: The size of prepared nanocomposites was 53.7 +/- 4.0 to 137.7 +/- 11.0 nm. The drug was released in a sustained manner till 120 h in phosphate buffer saline (pH 7.4) and acid phthalate buffer (pH 4.0). LAPDZ formulations inhibited acetylcholinesterase approximately by 82%, significantly higher (p < 0.05) than plain DZ (30%). Swiss albino mice exhibited enhanced brain uptake of LAPDZ administered via intravenous route. Promising pharmacokinetic parameters were observed in animals treated with LAPDZ. LAPDZ formulation showed half-life (t(1/2)), volume of distribution (Vd) and clearance (Cl) as 5.53 +/- 0.40 h(-1), 0.129 +/- 0.02 L, 0.015 +/- 0.002 L/h, respectively. While DZ solution showed the same parameters as 1.06 +/- 0.12 h(-1), 0.168 +/- 0.01 L, 0.106 +/- 0.013 L/h, respectively. The brain uptake of LAPDZ formulation was improved with quintuplet t(1/2). Conclusion: Based on the results of present study, it is proposed that the formulated nanocomposite would result in improved patient compliance with therapeutic effect at lower doses.