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<p>Lurasidone hydrochloride (LSD) is an atypical antipsychotic characterized by low oral bioavailability resulting from inadequate water solubility and significant first-pass metabolism, hence constraining its therapeutic effectiveness for central nervous system (CNS) disorders, including schizophrenia. Intranasal administration presents a viable alternative by circumventing the blood-brain barrier and improving cerebral targeting. A poloxamer-based mucoadhesive in-situ nasal gel containing Lurasidone-loaded solid lipid nanoparticles (LSD-SLNs) was formulated and refined to improve cerebral delivery. A 2³ complete factorial design was employed to optimize SLN parameters (lipid type, surfactant ratio, sonication duration). The evaluation included entrapment efficiency (EE%), particle size (PS), zeta potential (ZP), and in vitro release studies. The best formulation was examined by TEM. The enhanced solid lipid nanoparticles were integrated into in-situ gels using poloxamer 407 and HPMC as thermoresponsive agents and Carbopol 934P for its mucoadhesive properties. The formulations were evaluated for viscosity, pH, gelling temperature, spreadability, mucoadhesive strength, in vitro permeation (Franz diffusion), release kinetics, thermodynamic stability, and in vivo pharmacokinetics in rats. Optimized SLNs (F4) achieved a high EE% of 99.5%, a suitable particle size of 230&#xa0;nm, a zeta potential of -9.5 mV, and rapid in vitro release. The poloxamer-based gel (T4) exhibited a gelling temperature of 32&#xa0;°C and a spreadability of 6.5&#xa0;cm. In vitro permeation studies indicated approximately 96% drug release over 8&#xa0;h, following Korsmeyer–Peppas kinetics (<i>n</i> = 0.69). In vivo, T4 resulted in a 2.75-fold increase in AUC₀–∞ (2631.65 ± 60.11 ng·h/mL) and a 6.2-fold higher brain concentration at 24&#xa0;h compared with oral Latuda<sup>®</sup>.</p> Graphical Abstract <p></p>

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Factorial Design Approach for Formulation and Evaluation of Lurasidone HCl–Loaded Solid Lipid Nanoparticles in a Mucoadhesive Poloxamer Nasal Gel for Enhanced Nose-to-Brain Delivery

  • 期刊论文

  • 发表日期：

    2026年3月23日

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  • Sameh El Husseiny,
  • Mohamed El Nabarawi,
  • Rehab Abdelmonem

摘要

Lurasidone hydrochloride (LSD) is an atypical antipsychotic characterized by low oral bioavailability resulting from inadequate water solubility and significant first-pass metabolism, hence constraining its therapeutic effectiveness for central nervous system (CNS) disorders, including schizophrenia. Intranasal administration presents a viable alternative by circumventing the blood-brain barrier and improving cerebral targeting. A poloxamer-based mucoadhesive in-situ nasal gel containing Lurasidone-loaded solid lipid nanoparticles (LSD-SLNs) was formulated and refined to improve cerebral delivery. A 2³ complete factorial design was employed to optimize SLN parameters (lipid type, surfactant ratio, sonication duration). The evaluation included entrapment efficiency (EE%), particle size (PS), zeta potential (ZP), and in vitro release studies. The best formulation was examined by TEM. The enhanced solid lipid nanoparticles were integrated into in-situ gels using poloxamer 407 and HPMC as thermoresponsive agents and Carbopol 934P for its mucoadhesive properties. The formulations were evaluated for viscosity, pH, gelling temperature, spreadability, mucoadhesive strength, in vitro permeation (Franz diffusion), release kinetics, thermodynamic stability, and in vivo pharmacokinetics in rats. Optimized SLNs (F4) achieved a high EE% of 99.5%, a suitable particle size of 230 nm, a zeta potential of -9.5 mV, and rapid in vitro release. The poloxamer-based gel (T4) exhibited a gelling temperature of 32 °C and a spreadability of 6.5 cm. In vitro permeation studies indicated approximately 96% drug release over 8 h, following Korsmeyer–Peppas kinetics (n = 0.69). In vivo, T4 resulted in a 2.75-fold increase in AUC₀–∞ (2631.65 ± 60.11 ng·h/mL) and a 6.2-fold higher brain concentration at 24 h compared with oral Latuda®.

Graphical Abstract