Host–Guest Dynamic Behavior of Melatonin Encapsulated in β‑Cyclodextrin Nanosponges

Cyclodextrin-based nanosponges are cross-linked polymeric
porous
nanomaterials obtained by condensation of cyclodextrins with a polyfunctional
reagent (cross-linker). Owing to their high surface area, they are
attractive for encapsulation applications aimed at increasing the
stability, solubility, and bioavailability of drugs. Due to the structural
complexity of these emerging materials, computer modeling can provide
atomistic-level insights into both the flexibility of nanosponges
and their interactions with encapsulated drugs. In this contribution,
we focus on nanosponges of β-cyclodextrin cross-linked with
citric acid and provide full-atom models for linear and cyclic topologies.
We use extensive molecular dynamics (MD) simulations to analyze the
flexibility of these constructs and their interactions with encapsulated
melatonin, a neurohormone involved in sleep-wake cycle regulation
also used as an antioxidant and immunomodulator. We characterize the
main interactions responsible for melatonin binding and show that
it benefits from multivalence and crowding effects.