Development and Characterization of Citalopram-Loaded Thermosensitive Polymeric Micelles for Nasal Administration

Area of Science:

• * Pharmaceutical Sciences
• * Nanotechnology
• * Drug Delivery

Background:

• * Intranasal (IN) administration offers a non-invasive route for direct brain targeting, bypassing the blood-brain barrier.
• * Citalopram hydrobromide (CT), a selective serotonin reuptake inhibitor (SSRI), has limitations in oral/intravenous delivery, including delayed onset and poor patient compliance.
• * Sparingly water-soluble drugs like CT require advanced formulations to improve bioavailability and therapeutic efficacy.

Purpose of the Study:

• * To develop a novel thermoresponsive polymeric micelle (PM) system for intranasal delivery of citalopram hydrobromide (CT).
• * To enhance CT's solubility, stability, and nasal permeability using Pluronic® copolymers (F127 and Poloxamer 188).
• * To evaluate the potential of the developed nanosystem for improved antidepressant efficacy and patient compliance.

Main Methods:

• * Preparation of thermoresponsive polymeric micelles (PM) using the thin-film hydration method followed by freeze-drying.
• * Comprehensive characterization of optimized CT-PM formulation: particle size, polydispersity index (PdI), thermal behavior (LCST), encapsulation efficiency, XRPD, solubility, and stability.
• * In vitro assessment of CT release kinetics and CT permeability across nasal models.
• * Evaluation of formulation stability under storage conditions.

Main Results:

• * Optimized CT-PM formulation exhibited nanoscale size (31.41 nm), narrow distribution (PdI=0.241), and suitable LCST (~31 °C) for IN delivery.
• * Achieved ~90% encapsulation efficiency and a 95-fold increase in CT solubility due to the amorphous structure confirmed by XRPD.
• * Demonstrated a 25-fold increase in CT release rate and a four-fold enhancement in nasal permeability compared to initial CT.
• * Formulation showed good biological and physical stability, indicating suitability for storage and administration.

Conclusions:

• * The developed nanoscale thermosensitive PM formulation is a promising nasal drug delivery system.
• * This smart nanosystem significantly enhances CT solubility, stability, release rate, and nasal permeability.
• * The novel formulation offers a value-added strategy to overcome limitations of conventional CT administration, potentially improving therapeutic outcomes and patient compliance in depression management.