Engineered small extracellular vesicles as a versatile platform to efficiently load ferulic acid via an...

Area of Science:

• Biotechnology
• Nanomedicine
• Drug Delivery Systems

Background:

• Small extracellular vesicles (sEVs) are promising nano-drug carriers but face challenges in drug loading and encapsulation efficiency, particularly for hydrophilic drugs.
• Existing methods often yield insufficient loading and encapsulation rates, limiting their therapeutic potential.

Purpose of the Study:

• To develop an efficient and stable drug encapsulation platform for sEVs.
• To enhance the loading of hydrophilic small-molecule drugs into sEVs.
• To establish a novel method for producing high-quality, large-scale sEVs.

Main Methods:

• Development of an Esterase-responsive Active Loading (EAL) platform utilizing ferulic acid ester derivatives as prodrugs.
• Engineering sEVs to create a continuous transmembrane ion gradient for active drug loading.
• Characterization of sEVs using nano-flow cytometry and Malvern particle size analysis.
• Production of sEVs via differential ultracentrifugation and membrane filtration.

Main Results:

• The EAL platform demonstrated approximately 6-fold higher drug loading and 5-fold higher encapsulation efficiency compared to passive loading.
• Characterization confirmed large-scale, high-quality sEV production using the described methods.
• EAL-prepared sEVs loaded with ferulic acid exhibited superior slow release and low toxicity profiles in extracellular and intracellular assessments.

Conclusions:

• The EAL platform offers a significant improvement for efficient and stable drug encapsulation in sEVs, especially for hydrophilic drugs.
• The developed methods enable large-scale, high-quality production of sEVs for therapeutic applications.
• This study provides valuable insights for advancing sEV-based drug delivery systems.