Experimental and in silico studies of the encapsulation of Dopamine in cyclodextrin host-guest systems

Dopamine (DA) inclusion complexes were prepared with β-cyclodextrin (β-CD), hydroxypropyl-β-CD (HP-β-CD) and methyl-β-CD (Me-β-CD) to develop sustained-release nanosystems. This study provides a systematic experimental and in silico evaluation of DA–CD interactions, linking complex stoichiometry and physicochemical properties to the development of sustained-release DA nanocarriers. β-CD exhibited the highest performance, forming predominantly 1:2 host-guest complexes (β-CD: DA), with inclusion efficiency 59% and process yield 92%. The prepared inclusion complexes presented mean particle sizes ranging from 326.7 to 372.8 nm, polydispersity index (PdI) values between 0.347 and 0.399, and ζ-potential values from − 18.7 to − 40.4 mV, indicating the formation of nanosized colloidal systems with moderate size distribution and satisfactory colloidal stability. Chitosan-coated β-CD-DA nanoparticles demonstrated nanoscale size (323.6 nm), low polydispersity (0.301) and positive surface charge (+ 18.3 mV), confirming successful ionic-gelation coating. Spectroscopic and TGA analyses provided complementary evidence for β-CD–DA complex formation, while the NMR and MD results for HP-β-CD–DA suggested predominantly external associations rather than deep inclusion within the cyclodextrin cavity.In vitro release revealed rapid DA release (50–87% within 30 min) and complete release by 3 h, whereas chitosan-modified β-CD-DA nanocarriers achieved sustained release (52% at 5 h; 79% at 48 h). Release kinetics followed the Higuchi model (R²=0.768–0.949) and exhibited non-Fickian diffusion ( n > 0.5). The intermolecular interactions of inclusion complexes (ICs) were investigated by combining experimental and an in silico approach. As far as the latter is concerned, atomistic molecular dynamics simulations of the HP-β-CD-DA complex in an aqueous environment were carried out at the temperature and pressure of the experiments. The thermodynamic description of the systems was given in terms of standard binding Gibbs energies, and the comparison with experimental measurements shows good agreement. The computational study is complemented by the calculation of selected properties in order to shed light on the interactions between the constituent molecules of the HP-β-CD-DA complex.