β-Cyclodextrin/Isopentyl Caffeate Inclusion Complex: Synthesis, Characterization and Antileishmanial Activity

Area of Science:

• Medicinal Chemistry
• Drug Delivery Systems
• Parasitology

Background:

• Isopentyl caffeate (ICaf) is a natural bioactive compound with demonstrated efficacy against Leishmania.
• Poor aqueous solubility of ICaf limits its clinical application for treating leishmaniasis.
• Development of advanced drug delivery systems is crucial for improving ICaf's therapeutic potential.

Purpose of the Study:

• To enhance the solubility and bioavailability of isopentyl caffeate (ICaf) by forming an inclusion complex with beta-cyclodextrin (β-CD).
• To evaluate the efficacy of the ICaf:β-CD inclusion complex against Leishmania parasites.
• To optimize the preparation method and molar ratio for the ICaf:β-CD complex.

Main Methods:

• Inclusion complex formation using physical mixture (PM), kneading (KN), and co-evaporation (CO) methods.
• Characterization techniques including thermal analysis, FT-IR, SEM, and molecular docking.
• Solubility assays and in vitro cell proliferation assays against Leishmania species.

Main Results:

• The co-evaporation method yielded the optimal ICaf:β-CD complex at a 1:1 molar ratio with superior complexation.
• A significant increase in ICaf solubility was observed for the optimized ICaf:β-CD (CO, 1:1) complex.
• The ICaf:β-CD complex exhibited potent antiparasitic activity with IC50 values of 3.8 µg/mL for L. amazonesis and 2.7 µg/mL for L. chagasi.

Conclusions:

• The developed ICaf:β-CD inclusion complex effectively enhances ICaf solubility and bioavailability.
• The optimized complex demonstrates significant therapeutic potential for treating visceral and cutaneous leishmaniasis.
• This formulation offers a promising strategy for improving drug delivery and treatment outcomes for leishmaniasis.