Complexes between methyltestosterone and β-cyclodextrin for application in aquaculture production.

Area of Science:

• Pharmaceutical Chemistry
• Supramolecular Chemistry
• Aquaculture Science

Background:

• 17-alpha-methyltestosterone (MT) is an anabolic steroid with limited solubility, hindering its application.
• Beta-cyclodextrin (bCD) is a cyclic oligosaccharide known for its ability to form inclusion complexes and enhance the solubility of hydrophobic compounds.

Purpose of the Study:

• To prepare and characterize inclusion complexes of MT with bCD.
• To evaluate the impact of complexation on MT solubility and release kinetics.
• To explore potential applications of MT-bCD complexes in aquaculture.

Main Methods:

• Preparation and characterization of MT-bCD inclusion complexes using techniques like Differential Scanning Calorimetry (DSC), Nuclear Magnetic Resonance (NMR) spectroscopy (including DOSY-NMR and 2D-ROESY), and solubility studies.
• Molecular dynamics simulations to model the complex formation.
• In vitro release tests to assess drug release profiles.

Main Results:

• Complexation with bCD increased MT solubility sixfold.
• The stoichiometry of the inclusion complex was determined to be 2:1 (bCD:MT).
• High association constants (Ka = 2846 Lmol⁻¹ in DMSO/D₂O, 7540 Lmol⁻¹ in water) and a significant complex fraction (76%) were observed.
• Molecular dynamics simulations and ROESY experiments confirmed complete inclusion of MT within the bCD cavity.
• Complex formulations exhibited slower release rates compared to the free hormone.

Conclusions:

• MT forms stable inclusion complexes with bCD, significantly improving its solubility.
• The characterized MT-bCD complexes demonstrate controlled release properties.
• These formulations hold promise for aquaculture applications, including sex reversal and hormone sequestration in aquatic environments.