{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T08:24:53Z","timestamp":1793175893685,"version":"4.5.0"},"reference-count":89,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T00:00:00Z","timestamp":1771113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>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\u2019s 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.<\/jats:p>","DOI":"10.3390\/molecules31040675","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T14:55:47Z","timestamp":1771253747000},"page":"675","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["From PEGylation to Next-Generation Polymers: Overcoming Biological Barriers\u2014A Review"],"prefix":"10.3390","volume":"31","author":[{"given":"Rizvangul","family":"Iminova","sequence":"first","affiliation":[{"name":"Faculty of Chemistry and Chemical Technology, Al-Farabi Kazakh National University, Almaty 050040\/A15E3B4, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7213-7458","authenticated-orcid":false,"given":"Gulzat","family":"Berganayeva","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry and Chemical Technology, Al-Farabi Kazakh National University, Almaty 050040\/A15E3B4, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aliya","family":"Zhurtbayeva","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Department of Chemistry, Asfendiyarov Kazakh National Medical University, Almaty 050012\/A35B8H9, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lazzat","family":"Abdurakhmanova","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Department of Chemistry, Asfendiyarov Kazakh National Medical University, Almaty 050012\/A35B8H9, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Almagul","family":"Almabekova","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Department of Chemistry, Asfendiyarov Kazakh National Medical University, Almaty 050012\/A35B8H9, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0471-0587","authenticated-orcid":false,"given":"Daniil","family":"Shepilov","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry and Chemical Technology, Al-Farabi Kazakh National University, Almaty 050040\/A15E3B4, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulzira","family":"Vassilina","sequence":"additional","affiliation":[{"name":"Faculty of Biotechnology and Chemical Technologies, Almaty Technological University, Almaty 050012\/A05B8Y5, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akmaral","family":"Nurmahanova","sequence":"additional","affiliation":[{"name":"Faculty of Biology and Biotechnology, Al-Farabi Kazakh National University, Almaty 050040\/A15E3C7, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulfairuz","family":"Kairalapova","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry and Chemical Technology, Al-Farabi Kazakh National University, Almaty 050040\/A15E3B4, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moldyr","family":"Dyusebaeva","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry and Chemical Technology, Al-Farabi Kazakh National University, Almaty 050040\/A15E3B4, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5269","DOI":"10.1021\/acs.biomac.5c00766","article-title":"TCEP-Enabled Click Modification of Glycidyl-Bearing Polymers with Biorelevant Sulfhydryl Molecules: Toward Chemoselective Bioconjugation Strategies","volume":"26","author":"Porello","year":"2025","journal-title":"Biomacromolecules"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1080\/09205063.2020.1825304","article-title":"PEGylation: An Important Approach for Novel Drug Delivery System","volume":"32","author":"Yadav","year":"2021","journal-title":"J. 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