NAG-PEGylated multilamellar liposomes for BBB-GLUT transporter targeting

Area of Science:

• * Pharmaceutical Sciences
• * Nanotechnology
• * Neuroscience

Background:

• * The Blood-Brain Barrier (BBB) restricts the passage of many therapeutic agents into the brain.
• * Targeting Glucose (GLUT) transporters presents a potential strategy to enhance drug permeability across the BBB.
• * Citalopram hydrobromide (Citalopram-Hbr) is a drug with potential for BBB targeting.

Purpose of the Study:

• * To develop and characterize N-Acetyl Glucosamine (NAG) coated PEGylated liposomal formulations of Citalopram-Hbr.
• * To evaluate the in-vitro cytotoxicity and BBB permeability of these novel liposomal formulations.
• * To investigate the potential of these formulations for GLUT transporter-mediated drug delivery across the BBB.

Main Methods:

• * Preparation and physicochemical characterization of five NAG-coated PEGylated multilamellar liposomal formulations.
• * Cytotoxicity assessment using Rat Primary Brain Microvascular Endothelial Cells (RPBECs).
• * In-vitro drug permeability studies using RPBECs monolayers to determine apparent drug permeability (Papp).

Main Results:

• * Successful synthesis of NAG-coated PEGylated liposomes with particle sizes ranging from 13 to 4259 nm and high entrapment efficiency (50-75%).
• * Formulations exhibited excellent biocompatibility with RPBECs, showing >90% cell viability at concentrations up to 1.25 mg/ml.
• * Significant in-vitro drug permeability across RPBECs monolayers was observed, with Papp values ranging from 5.01 × 10^4 to 15 × 10^4 cm/min.

Conclusions:

• * NAG-coated PEGylated liposomal formulations of Citalopram-Hbr were successfully developed.
• * The formulations demonstrated good safety profiles and enhanced drug permeability, suggesting potential for BBB targeting.
• * RPBEC monolayers serve as an effective model for screening drug transport studies targeting BBB GLUT transporters.