Development and Optimization of 7,8-Dihydroxyflavone-Loaded Polylysine/Lecithin Nanoparticles for Potential...

Area of Science:

• Neuroscience and Pharmacology
• Nanotechnology and Drug Delivery
• Biochemistry

Background:

• The neuroprotective agent 7,8-dihydroxyflavone (7,8-DHF) shows therapeutic promise but suffers from poor solubility, rapid metabolism, and low bioavailability.
• Nanotechnology offers solutions for enhancing drug stability, bioavailability, and enabling nose-to-brain delivery.
• Developing effective delivery systems for neuroprotective agents like 7,8-DHF is crucial for treating neurological disorders.

Purpose of the Study:

• To develop and optimize lipid nanoparticles (LNPs) for the intranasal delivery of 7,8-dihydroxyflavone (7,8-DHF).
• To characterize the physicochemical properties, stability, and biological activity of the 7,8-DHF-loaded LNPs.
• To evaluate the potential of the nanoformulation for enhanced nose-to-brain transport of 7,8-DHF.

Main Methods:

• Lipid nanoparticles encapsulating 7,8-DHF were formulated using a fish-oil-based lipid core and natural excipients.
• A Design of Experiments (DoE) approach optimized formulation parameters including drug concentration, lecithin, and surfactant type.
• Characterization involved particle size, PDI, zeta potential, encapsulation efficiency, TEM imaging, stability studies, mucin interaction, DPPH assay, and in vitro cytotoxicity on olfactory ensheathing cells.

Main Results:

• Optimized nanoparticles achieved nanometric size (<250 nm) with spherical morphology and low polydispersity (PDI < 0.3).
• The nanoformulation demonstrated good physicochemical stability in simulated biological fluids for 48 hours and favorable interaction with mucus.
• In vitro studies confirmed ROS scavenging capacity and reduced cytotoxicity of encapsulated 7,8-DHF compared to the free drug.

Conclusions:

• The developed lipid nanoparticles show promise for the effective intranasal delivery of 7,8-dihydroxyflavone (7,8-DHF).
• This nanoformulation addresses the pharmacokinetic limitations of 7,8-DHF, potentially improving its therapeutic efficacy.
• The study supports the application of this nanotechnology-based approach for targeted brain delivery of neuroprotective agents.