Piperazine-Functionalized Nanoparticles Enable Oral Insulin Delivery in Obese Mice

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Nanotechnology

Background:

• Biologics are crucial therapeutics but often require parenteral administration due to poor oral absorption.
• Current oral delivery methods using nanoparticles or chemical permeation enhancers (PEs) have limitations in efficacy and safety.
• 1-phenylpiperazine (PPZ) is an effective PE but exhibits toxicity at therapeutic doses.

Purpose of the Study:

• To develop a safe and effective nanoparticle-based permeation enhancer for oral biologic delivery.
• To investigate the efficacy of PPZ-grafted silica nanoparticles in enhancing macromolecule intestinal permeation.
• To evaluate the in vivo safety and efficacy of oral insulin delivery using these novel nanoparticles.

Main Methods:

• Synthesized silica nanoparticles grafted with 1-phenylpiperazine (PPZ).
• Assessed macromolecule permeation using in vitro Caco-2 monolayer and co-culture models.
• Evaluated in vivo permeation of FITC-dextran-4 kDa in mice and insulin absorption in a high-fat diet mouse model.

Main Results:

• PPZ-grafted silica nanoparticles significantly enhanced insulin permeation in vitro without apparent toxicity.
• In vivo studies demonstrated improved FITC-dextran-4 kDa permeation compared to bare silica nanoparticles.
• Oral administration of insulin with silica-PPZ nanoparticles in mice led to sustained blood glucose reduction without observed toxicity.

Conclusions:

• PPZ-grafted silica nanoparticles represent a safe and effective permeation enhancer for oral biologic delivery.
• This novel approach holds potential for improving the oral administration of insulin and other biologics.
• The developed system overcomes limitations of existing PEs, offering a promising alternative to injections.