# From PEGylation to Next-Generation Polymers: Overcoming Biological Barriers—A Review

## TL;DR

This paper reviews how new polymers are replacing PEG in drug delivery to improve safety and effectiveness.

## Contribution

The paper presents a comprehensive review of next-generation polymers designed to overcome PEG's limitations in drug delivery.

## Key findings

- PEG's use is being challenged due to immunogenicity and limited biodegradability.
- New polymers offer better biocompatibility and control over drug delivery.
- These advances signal a shift toward safer and more versatile therapeutic systems.

## Abstract

Poly(ethylene glycol) (PEG) has long stood as the prevailing standard in drug delivery, celebrated for its capacity to enhance solubility, extend circulation, and improve pharmacological performance. Nevertheless, the emergence of anti-PEG antibodies, accelerated clearance, and limited biodegradability increasingly undermine its role as a universal solution. In response, a new generation of polymers has been developed to address these shortcomings, offering the potential to sustain or surpass PEG’s benefits while mitigating immunogenicity, improving biocompatibility, and enabling finer control over therapeutic fate. This review examines current research to articulate a coherent perspective on the replacement of PEG, tracing how advances in polymer design are reshaping the foundations of targeted drug delivery. Taken together, these developments signal not only a corrective to the limitations of PEG but also a broader paradigm shift toward safer, more versatile, and clinically translatable systems that define the next frontier in precision therapeutics.