An Enteric-Coated Polyelectrolyte Nanocomplex Delivers Insulin in Rat Intestinal Instillations when Combined with a...

Area of Science:

• Biomaterials Science
• Nanotechnology for Drug Delivery
• Pharmacology

Background:

• Oral delivery of peptides like insulin is challenging due to degradation and poor absorption.
• Nanocarriers offer a potential solution for enhancing oral peptide bioavailability.
• Polyelectrolyte complexes (PECs) are investigated for their ability to encapsulate and protect therapeutic payloads.

Purpose of the Study:

• To develop and characterize insulin-loaded anionic polyelectrolyte nanoparticle complexes (PECs) for oral delivery.
• To evaluate the stability, release kinetics, and in vivo efficacy of coated and uncoated PECs.
• To investigate the role of permeation enhancers in improving oral insulin delivery via PECs.

Main Methods:

• Insulin-associated PECs were formed using hyaluronic acid and chitosan, coated with Eudragit® L-100, and characterized by DLS, NTA, and HPLC.
• In vitro studies included dissolution in simulated intestinal fluid (FaSSIF-V2), pancreatin stability tests, mucin interaction, and Caco-2 cell cytotoxicity.
• In vivo studies involved jejunal instillation in rats, with and without sucrose laurate as a permeation enhancer, monitoring plasma glucose levels.

Main Results:

• Insulin-loaded PECs exhibited high association efficiency (>95%) and loading (~83 µg/mg), with optimal size (95-200 nm) and negative zeta potential (-40 to -50 mV).
• Coated PECs demonstrated delayed insulin release and enhanced protection against enzymatic degradation compared to uncoated PECs.
• While uncoated and coated PECs alone failed to reduce plasma glucose in rats, co-administration with sucrose laurate resulted in a 70% reduction in blood glucose.

Conclusions:

• Anionic PECs, particularly when coated with pH-dependent polymers, can effectively encapsulate and protect insulin.
• The addition of a permeation enhancer (sucrose laurate) was crucial for enabling the oral absorption of insulin from PECs.
• This study highlights the potential of combining nanocarrier systems with permeation enhancers for successful oral peptide delivery.