A Review: Comparison of PEGylation Methods in Efforts to Improve the Bioavailability Profile of Oral Products Based on Insulin, Peptides, and Therapeutic Proteins

Halim Fatan Machmud; Salsa Aulia Rossyana; Alyaa Sekar Kemuning; Early Syifa Insani; Rizqi Amalia

Authors

Halim Fatan Machmud Universitas Jenderal Soedirman
Salsa Aulia Rossyana
Alyaa Sekar Kemuning
Early Syifa Insani
Rizqi Amalia

Keywords:

PEGylation, biopharmaceutical, biopharmaceuticals, oral

Abstract

PEGylation is a promising strategy for improving the oral delivery of biopharmaceuticals, which often experience instability, enzymatic degradation, and low permeability in the gastrointestinal tract. This review aims to evaluate various PEGylation approaches and their effectiveness in improving the bioavailability profile of orally administered biopharmaceuticals. The study employed a narrative literature review method, collecting research articles from PubMed and ScienceDirect over the past ten years. Selection was performed using predetermined inclusion and exclusion criteria, followed by full-text assessment and thematic synthesis. The results of the study show that PEGylation can improve gastrointestinal stability, protect against proteolysis, modify physicochemical properties, and increase cellular uptake through mechanisms such as steric protection, increased hydrophilicity, and the formation of PEG-based delivery systems. Various PEG systems, including nanocarriers, niosomes, conjugated polymers, and microbial platforms, generally showed better structural and functional integrity compared to formulations without PEGylation. Several studies also reported increased mucosal adhesion, longer intestinal retention time, and stable biological activity under simulated digestive conditions. Overall, PEGylation has proven to be an effective and versatile modification strategy to support the development of oral biopharmaceuticals.

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