Drug-Inspired Design of Supramolecular Polymers for Enhanced Drug Loading and Sustained Therapeutic Release

Authors

Boran Sun, Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland 21218, United States.
Mi-Kyung Shin, Department of Anesthesiology and Critical Care Medicine, George Washington University School of Medicine and Health Sciences, Washington, District of Columbia 20037, United States.
Meng Qin, Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland 21218, United States.
Caleb F. Anderson, Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland 21218, United States.
Tian Xu, Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland 21218, United States.
Jiarui Yang, Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland 21218, United States.
Claire Sklar, Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland 21218, United States.
Vsevolod Y. Polotsky, Department of Anesthesiology and Critical Care Medicine, George Washington University School of Medicine and Health Sciences, Washington, District of Columbia 20037, United States.
Honggang Cui, Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland 21218, United States.

Document Type

Journal Article

Publication Date

6-30-2025

Journal

ACS nano

DOI

10.1021/acsnano.5c02462

Keywords

controlled release; drug delivery; fingolimod; hydrogels; hypertension; supramolecular polymers

Abstract

Supramolecular polymeric hydrogels have emerged as a dynamic, versatile platform for localized therapeutic delivery, leveraging reversible and tunable noncovalent interactions. Despite their potential, designing supramolecular polymers that combine high drug loading with sustained, controlled release remains a considerable challenge. Here, we introduce a series of drug-inspired, peptide-based monomers engineered as supramolecular hydrogelators to facilitate high-affinity coassembly with therapeutic agents. By strategically utilizing electrostatic complexation and π-π stacking interactions, these hydrogelators self-assemble into robust supramolecular polymer networks with well-defined nanostructures, achieving nearly 100% fingolimod loading efficiency and extremely high loading capacity (up to approximately 32% by mass). Our results demonstrate that these tailored supramolecular interactions not only enhance the fingolimod drug loading efficiency and capacity, but also modulate the self-assembly and dissociation process, enabling prolonged and predictable drug release both in vitro and in vivo. We believe this work advances the field of supramolecular polymers by integrating drug-inspired molecular design principles and contributes to the development of advanced drug delivery systems with broader biomedical applications.

APA Citation

Sun, Boran; Shin, Mi-Kyung; Qin, Meng; Anderson, Caleb F.; Xu, Tian; Yang, Jiarui; Sklar, Claire; Polotsky, Vsevolod Y.; and Cui, Honggang, "Drug-Inspired Design of Supramolecular Polymers for Enhanced Drug Loading and Sustained Therapeutic Release" (2025). GW Authored Works. Paper 7352.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/7352

Department

Anesthesiology and Critical Care Medicine