Scalable Preparation of Extracellular Vesicles Encapsulating Anticancer Drugs by High-Pressure Homogenization for...

Area of Science:

• Biotechnology
• Nanomedicine
• Cancer Therapy

Background:

• Extracellular vesicles (EVs) show promise for drug delivery but face challenges in scalability and drug encapsulation efficiency.
• Conventional methods limit clinical translation of EV-based therapeutics.
• Lipid-based nanoparticles manufacturing success suggests high-pressure homogenization (HPH) as a scalable alternative for EV drug loading.

Purpose of the Study:

• To investigate the utility of HPH for scalable preparation of paclitaxel (PTX)-encapsulated EVs (mEVs).
• To evaluate the efficacy of HPH-produced EV therapeutics in targeted cancer therapy.
• To optimize HPH conditions for efficient drug encapsulation and scale-up.

Main Methods:

• Paclitaxel (PTX) was encapsulated into bovine milk-derived EVs (mEVs) using HPH with distearoylphosphatidylethanolamine-polyethylene glycol (DSPE-PEG).
• Laboratory-scale HPH was optimized and scaled up to a 100 mL industrial process.
• EVs were further modified with cyclo(Arg-Gly-Asp-d-Phe-Lys) (cRGD) grafted DSPE-PEG for targeted delivery.

Main Results:

• Efficient encapsulation of PTX into mEVs was achieved using HPH.
• Scalable preparation of PEG-modified PTX-encapsulated mEVs (PTX-mEVs) was demonstrated at a 100 mL scale.
• cRGD-modified PTX-mEVs showed enhanced PTX delivery to cancer cells and significantly suppressed tumor growth in mice.
• cRGD-modified PTX-mEVs exhibited superior antitumor efficacy compared to PEG-modified PTX-mEVs.

Conclusions:

• HPH is a viable one-step method for scalable production of drug-encapsulated EV therapeutics.
• The developed EV therapeutics demonstrate potential for effective targeted cancer therapy.
• HPH offers a promising approach for the clinical translation of EV-based drug delivery systems.