Comparative Evaluation of Conventional Host‐Guest Inclusion Complex & Sustainable Resveratrol Loaded Hydroxypropyl‐β‐Cyclodextrin Nanosponges With Improved Therapeutic Potential

ABSTRACT Resveratrol, a polyphenolic compound, exhibits anticarcinogenic properties to target all major stages of cancer. Cyclodextrin‐based inclusion complexes and nanosponges are effective for delivering various therapeutic agents; cyclodextrin derivative‐based sustainable nanosponges remain largely unexplored, particularly for resveratrol. The present study develops hydroxypropyl‐β‐cyclodextrin carbonate nanosponges (Res‐HPβNS) using deep eutectic solvents (DES) based on choline chloride and zinc chloride, replacing conventional petroleum‐based solvents to achieve more eco‐friendly pharmaceutical standards and comparatively explore their potentials versus resveratrol‐hydroxypropyl‐β‐cyclodextrin host‐guest inclusion complexes (Res‐HPβCD). Res‐HPβCD and Res‐HPβNS were developed, characterized, and assayed for loading capacity, drug release kinetics, antioxidant activity, and antiproliferative effects. SEM, FTIR, XRD, and DSC studies confirmed the formulation of Res‐HPβCD and Res‐HPβNS. The polymers obtained 445.33 ± 1.99 nm as mean particle size and −15.63 ± 2.14 mV zeta potential. Additionally, these sustainable Res‐HPβNS offered significant advantages over Res‐HPβCD, featuring 3.71‐times enhancement in loading capacity accompanied by a sustained release profile (compared to the burst release pattern of the host‐guest complex), greater free radical scavenging activity, and up to a 1.63‐fold enhancement in antiproliferative efficiency targeting MCF‐7 breast cancer cell lines. Overall, compared to Res‐HPβCD, a green nanosponge‐based approach may serve as a pharmaceutically compatible and effective nanocarrier for potential cancer therapy.