Design, Optimization, and In Vitro Evaluation of Lactoferrin-Coated Brexpiprazole-Loaded Nanostructured Lipid...

Area of Science:

• Nanotechnology
• Pharmaceutics
• Drug Delivery Systems

Background:

• Brexpiprazole is an antipsychotic medication.
• Nanostructured lipid carriers (NLCs) offer potential for enhanced drug delivery.
• Targeted brain delivery remains a challenge for many CNS-acting drugs.

Purpose of the Study:

• To develop and optimize lactoferrin-coated Brexpiprazole-loaded nanostructured lipid carriers (Lf-BXP-NLCs).
• To enhance brain targetability and prolong the residence time of Brexpiprazole.
• To utilize a Design of Experiments (DoE) approach combined with an artificial neural network (ANN) for formulation optimization.

Main Methods:

• In silico molecular docking to assess drug-lipid interactions.
• NLCs prepared using hot high-speed homogenization.
• Plackett-Burman and Box-Behnken designs for screening and optimization of formulation and process variables.
• ANN model development for predicting particle size and drug release.
• Comprehensive characterization including physicochemical properties, morphology, in vitro release, and ex vivo studies.

Main Results:

• Favorable in silico interactions between Brexpiprazole and selected lipids/surfactants.
• Liquid lipid content identified as the most critical factor influencing particle size and drug release.
• Optimized Lf-BXP-NLCs achieved particle size of 132.8 nm, high entrapment efficiency (87.8%), and drug loading (11.71%).
• Demonstrated extended drug release profile and enhanced permeation flux.

Conclusions:

• Successful optimization of Lf-BXP-NLCs using an integrated DoE-ANN approach.
• The optimized formulation exhibited excellent physicochemical properties, compatibility, and sustained release.
• Lf-BXP-NLCs show significant promise for targeted nose-to-brain delivery of Brexpiprazole.