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Enzyme-Mediated Dynamic Combinatorial Chemistry Enables Large-Scale Synthesis of δ-Cyclodextrin.

Journal of the American Chemical Society2025-04-09PubMed
Total: 88.5Innovation: 9Impact: 8Rigor: 9Citation: 9

Summary

This paper establishes the first scalable, high-yield (>40%) and high-purity (>95% without chromatography) synthesis of δ-cyclodextrin (nine glucose units) using enzyme-mediated dynamic combinatorial chemistry and a dodecaborate template. The method enables multigram production, unlocking applications in cosmetics and pharmaceuticals for encapsulating actives, improving stability, and controlled release.

Key Findings

  • Introduces a scalable synthesis of δ-cyclodextrin with >40% yield and >95% purity without chromatography
  • Achieves multigram quantities using enzyme-mediated dynamic combinatorial chemistry and a dodecaborate template
  • Positions δ-CD for applications as a host carrier in foods, cosmetics, and pharmaceuticals

Clinical Implications

While not a clinical study, δ-cyclodextrin may enable safer and more effective topical/cosmeceutical products via improved solubilization and stabilization of active ingredients; toxicology and dermal safety testing will be required before clinical use.

Why It Matters

By overcoming a long-standing scalability barrier, this work provides a foundational excipient platform with direct translational potential in cosmeceutical and pharmaceutical formulation science.

Limitations

  • Lacks pharmacokinetic/toxicological data for dermal or systemic exposure
  • Industrial cost and environmental impact of the superchaotropic template are not evaluated

Future Directions

Evaluate δ-CD toxicology, dermal compatibility, and performance as a carrier for cosmetic actives; scale-up beyond multigram and lifecycle assessments to support regulatory adoption.

Study Information

Study Type
Case series
Research Domain
Pathophysiology
Evidence Level
V - Laboratory synthesis/chemical methodology; preclinical foundational evidence
Study Design
OTHER