A quality-by-design engineering strategy for hybrid lipid-random copolymer nanoparticles optimization: methotrexate...

Area of Science:

• Pharmaceutical Science
• Materials Science
• Biotechnology

Background:

• Hybrid nanoparticles offer a promising platform for drug delivery, but their complex nature necessitates rational design strategies.
• Quality by Design (QbD) principles are crucial for developing predictable and effective pharmaceutical formulations, especially for complex nanocarriers.
• Phospholipids and random copolymers represent key components in advanced drug delivery systems.

Purpose of the Study:

• To develop and optimize hybrid nanoparticles incorporating a model hydrophobic drug (methotrexate) using QbD principles.
• To investigate the influence of formulation variables, such as copolymer concentration and drug loading, on nanoparticle quality attributes.
• To evaluate the stability and in vitro anticancer efficacy of the optimized hybrid nanoparticles.

Main Methods:

• Hybrid nanoparticles were formulated using 1,2-dioctadecanoyl-sn-glycero-3-phosphocholine and a random copolymer of oligo(ethylene glycol) methyl ether methacrylate and lauryl methacrylate.
• Critical formulation variables (copolymer concentration, drug content) were systematically studied to optimize nanoparticle characteristics.
• Nanoparticle stability was assessed under storage and biorelevant conditions.
• In vitro anticancer efficacy was evaluated using primary glioblastoma cells.

Main Results:

• Optimized hybrid nanoparticles were successfully developed, demonstrating controlled drug incorporation.
• Formulation variables significantly impacted key quality attributes, enabling rational optimization.
• The nanoparticles exhibited adequate stability under tested conditions.
• Promising in vitro anticancer activity was observed against glioblastoma cells.

Conclusions:

• The QbD approach facilitated the rational design and optimization of hybrid nanoparticles for drug delivery.
• The combination of phospholipids and random copolymers provides a versatile platform for developing effective nanomedicines.
• These hybrid nanoparticles show significant potential for targeted anticancer therapy, particularly for glioblastoma.