Cyclodextrin-based nanosponge for improvement of solubility and oral bioavailability of Ellagic acid

Abstract

Ellagic acid (EA) is a polyphenolic compound, naturally occurring in various fruits. It has antioxidant, anticancer and antimutagenic properties. Its low aqueous solubility and permeability in GIT, permanent binding to DNA and proteins of cells and first pass metabolism are considered as the reasons for its low oral bioavailability and consequently its low therapeutic potential. Cyclodextrin-based nanosponges (NS) have been utilized to improve the solubilization efficiency of Ellagic acid and to control its release. The scope of the work was to prepare EA nanosponges (EA-NS) using cyclodextrin (β-CD) and cross-linked by dimethyl carbonate (DMC). It was found that the particle size of the prepared EA-NS was 423.2 nm with low polydispersity index (0.409) and high zeta potential (-34 mV) which manifests the construction of a stabilized colloidal nanoformulation. Moreover, high solubilization efficiency of the loaded EA-NS (49.79µg/ml) compared with the free EA (9.73µg/ml) was spotted. The prepared EA-NS was characterized by XRD, FTIR, and DSC studies and it elucidated a definite interaction of EA with NS. EA-NS successively improved its solubility and provided a controlled in vitro release for 24 hours. EA-NS produced about 69.17 % drug content which indicates a good drug loading of the prepared nanosponges. Dissolution of EA-NS was higher than the drug alone. Animal study displayed an improvement in the oral bioavailability of EA indicated by an increase in AUC (1345.49 ng.hr.ml-1) of the EA -NS compared with (598.94 ng.hr.ml-1) for EA.