Stimuli-responsive cyclodextrin-based supramolecular assemblies as drug carriers

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In this review with 169 references, the recent advances in stimuli-responsive supramolecular assemblies based on the host–guest chemistry of CDs war summarize. The stimuli considered in this review include endogenous (pH, redox, and enzymes) and exogenous stimuli (light, temperature, and magnetic field). The mechanisms of the stimuli-responsive ability are discussed and typical designs of the corresponding supramolecular assemblies for drug delivery and other potential biomedical applications are presented. The limitations and perspectives of CD-based stimuli-responsive supramolecular assemblies are discussed to further promote the translation of laboratory products into clinical applications.

Versatile functions can be integrated into one supramolecular system in a facile manner by modifying
the functional moieties with CDs or guest molecules. The CD-based stimuli-responsive supramolecular assemblies are potentially useful for precise drug delivery, and antibacterial, and other tissue engineering applications. However, several challenges remain,
(1) Although CD-based stimuli-responsive supramolecular assemblies exhibit apparent advantages, most CD-based systems are produced at the laboratory level. This results from the complex synthesis routes of materials and the post-processing procedures, which lead to poor reproducibility; this may hamper their clinical translation. In addition, it is critical to examine the biosafety and biocompatibility of materials.
(2) Considering that it is difficult to avoid using auxiliary additives with trace toxicity, in vivo safety should be evaluated systemically.
(3) The human body is a complex organism whose internal environment is dynamically maintained in homeostasis; thus, to some extent, endogenous stimuli-responsive systems are uncontrollable and not precise. In a multifunctional system, this unstable response could lead to the inactivity of active moieties.
(4) Although endogenous responsive systems do not rely on the physiological environment, the ability of exogenous stimulus signals to penetrate tissue is weak. In this sense, exogenous stimuli-responsive systems are limited to treating diseases whose lesion sites are in superficial regions. Furthermore, tissue damage from exogenous stimulation must be confirmed to be negligible or at least at the restorative level.

Ying Yuan, Tianqi Nie, Yifen Fang, Xinru You, Hai Huang and Jun Wu: Stimuli-responsive cyclodextrin-based supramolecular assemblies as drug carriers. J. Mater. Chem. B, 2022,10, 2077-2096

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