Polyester-based long acting injectables: Advancements in molecular dynamics simulation and technological insights

Area of Science:

• Polymer science and drug delivery systems
• Biocompatible materials for sustained release therapeutics
• Pharmaceutical formulation and manufacturing

Background:

• Long-acting injectable (LAI) technologies enhance patient compliance by providing therapeutic delivery over weeks to months.
• Polyester-based LAI systems, especially poly(lactic-co-glycolic acid) (PLGA), have advanced significantly due to favorable properties like biocompatibility and tunable degradation.
• PLGA's extensive clinical validation supports its role in developing effective LAI products.

Purpose of the Study:

• To review the properties and development of poly(lactic-co-glycolic acid) (PLGA) for long-acting injectable (LAI) drug delivery.
• To explore the application of molecular dynamic simulations in understanding polymer-drug interactions within LAI systems.
• To provide an overview of current and emerging PLGA-based and non-PLGA LAI technologies, including their design, delivery, and challenges.

Main Methods:

• Literature review focusing on poly(lactic-co-glycolic acid) (PLGA) properties and LAI development.
• Discussion of molecular dynamic simulations for polymer-drug interaction analysis.
• Comparative analysis of various advanced PLGA-based and non-PLGA LAI technologies.

Main Results:

• Poly(lactic-co-glycolic acid) (PLGA) demonstrates excellent biocompatibility, formulation flexibility, and controllable degradation rates, making it ideal for LAI development.
• Molecular dynamic simulations offer insights into polymer-drug interactions, crucial for optimizing LAI quality attributes and drug release profiles.
• A broad spectrum of PLGA-based LAI technologies, alongside select non-PLGA alternatives, are presented, detailing their progression from lab to clinical application.

Conclusions:

• Poly(lactic-co-glycolic acid) (PLGA) remains a cornerstone technology for advanced long-acting injectable (LAI) drug delivery systems.
• Integrating computational simulations with experimental data is key to refining LAI design and predicting performance.
• Successful commercialization of LAIs hinges on addressing technical challenges and aligning product design with end-user needs.