Enhanced Oral Delivery of Asenapine Maleate from Solid Lipid Nanoparticles: Pharmacokinetic and Brain Distribution Evaluations

Abstract

Introduction: The aim of the present research work was to develop asenapine maleate (AM)-loaded solid
lipid nanoparticles (AM-SLN) for the enhancement of oral bioavailability of drug and delivery to the brain.
Materials and Methods: A 32 factorial design was used for the development and optimization of AM-SLN. Two
independent variables, drug:lipid ratio (X1) and number of homogenization cycles (X2), were selected, while
particle size and entrapment efficiency were selected as response variables. The optimized batch was evaluated
by various in vitro characterizations and in vivo pharmacokinetic and brain distribution studies. Results: The
particle size, polydispersity index, entrapment efficiency, and zeta potential of optimized AM-SLN were found to
be 113 ± 4 nm, 0.34 ± 0.05, 72.4 ± 1.73%, and −41.4 ± 2.25 mV, respectively. Pharmacokinetic study indicated
significantly higher (P < 0.05) peak drug concentration (142.41 ± 8.14 ng/mL), area under the drug concentrationtime
curve (1561.81 ± 36.34 h ng/mL), and mean residence time (15.31 ± 3.21 h) of AM-SLN compared to
AM-suspension (77.02 ± 5.74 ng/mL, 299.76 ± 39.42 ng/mL, and 2.73 ± 0.16 h, respectively) through oral route.
Brain distribution study showed higher drug permeation across the blood–brain barriers and accumulation in the
brain. Conclusion: These findings demonstrate that SLNs could be a new promising drug delivery system for oral
delivery of AM in the treatment of schizophrenia.