From PEGylation to Next-Generation Polymers: Overcoming Biological Barriers—A Review
Iminova R. Berganayeva G. Zhurtbayeva A. Abdurakhmanova L. Almabekova A. Shepilov D. Vassilina G. Nurmahanova A. Kairalapova G. Dyusebaeva M.
February 2026Multidisciplinary Digital Publishing Institute (MDPI)
Molecules
2026#31Issue 4
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.
biodegradable polymers , low-immunogenic polymers , nanocarriers , PEG alternatives , targeted cancer therapy
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Faculty of Chemistry and Chemical Technology, Al-Farabi Kazakh National University, Almaty, 050040/A15E3B4, Kazakhstan
School of Pharmacy, Department of Chemistry, Asfendiyarov Kazakh National Medical University, Almaty, 050012/A35B8H9, Kazakhstan
Faculty of Biotechnology and Chemical Technologies, Almaty Technological University, Almaty, 050012/A05B8Y5, Kazakhstan
Faculty of Biology and Biotechnology, Al-Farabi Kazakh National University, Almaty, 050040/A15E3C7, Kazakhstan
Faculty of Chemistry and Chemical Technology
School of Pharmacy
Faculty of Biotechnology and Chemical Technologies
Faculty of Biology and Biotechnology
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