Engineered extracellular vesicles loaded in boronated cyclodextrin framework for pulmonary delivery.

Area of Science:

• Biomaterials Science
• Nanotechnology
• Pulmonary Drug Delivery

Background:

• Extracellular vesicles (EVs) show therapeutic potential but suffer from rapid clearance and poor targeting.
• Pulmonary drug delivery offers localized treatment for respiratory diseases, minimizing systemic toxicity.
• Developing effective carriers for pulmonary delivery of EVs is crucial for enhancing therapeutic outcomes.

Purpose of the Study:

• To engineer a novel drug delivery system for pulmonary administration of modified EVs.
• To investigate the pH/H2O2 responsive release of EVs from a boronated cyclodextrin framework (BCF).
• To evaluate the efficacy and biocompatibility of RGD-modified EVs loaded in BCF for lung disease therapy.

Main Methods:

• Preparation of a boronated cyclodextrin framework (BCF) for encapsulating EVs.
• Modification of milk-derived EVs (mEVs) with cyclo(Arg-Gly-Asp-D-Tyr-Lys) peptide (RGD).
• Loading of RGD-modified mEVs into BCF to form RGD-mEVs@BCF.
• In vitro assessment of anti-inflammatory activity and in vivo biocompatibility studies in rats.

Main Results:

• RGD-mEVs demonstrated enhanced anti-inflammatory activity compared to unmodified mEVs in vitro.
• BCF effectively captured and protected RGD-mEVs, enabling sustained and responsive release.
• Pulmonary administration of RGD-mEVs@BCF exhibited favorable biocompatibility in a rat model.

Conclusions:

• RGD-mEVs@BCF serves as a biocompatible platform for pulmonary drug delivery.
• The pH-responsive release of EVs from BCF enhances therapeutic potential for lung diseases.
• This system shows promise for treating inflammatory lung conditions through targeted pulmonary delivery.