Biocompatible supramolecular inclusion complexes of β-cyclodextrin with protocatechuic acid ethyl ester: Increased solubility, stability and antioxidant activity

Abstract

Protocatechuic acid ethyl ester (EDHB) exhibits significant antioxidant, antimicrobial, neuroprotective, and cardioprotective activities. However, its limited water solubility restricts its bioavailability and therapeutic potential. This study aimed to improve the solubility and stability of EDHB by forming inclusion complexes (ICs) with (3-cyclodextrin ((3-CD) using the solvent evaporation method. The EDHB loading capacity of the ICs was 12.2 %, with an inclusion ratio of 71.4 %. Phase solubility studies and MALDI-TOF MS analysis confirmed a 1:1 stoichiometric complexation. Characterization via FT-IR, XRD, and SEM verified successful IC formation. pH and thermal stability studies indicated enhanced stability of ICs compared to free EDHB. The antioxidant activity assessed via DPPH assay revealed that the IC50 value of EDHB/(3-CD ICs (0.038 mM) was approximately three times lower than free EDHB (0.116 mM), demonstrating improved antioxidant potency. MTT assays on healthy human dermal fibroblast cells confirmed over 90 % cell viability at effective antioxidant doses, indicating excellent biocompatibility. These findings suggest that EDHB/(3-CD ICs could serve as a promising biocompatible formulation for oxidative stress-related therapies.