Modeling a pH-sensitive Zein-co-acrylic acid hybrid hydrogels loaded 5-fluorouracil and rutin for enhanced anticancer efficacy by oral delivery

Abstract

The combination of natural and synthetic polymeric materials grafted hydrogels offer great potential as oral therapeutic systems because of its intrinsic biocompatibility, biodegradability, protect labile drugs from metabolism and controlled release properties. Hence, in the present study, we aimed to prepare and optimize oral delivered pH-responsive Zein-co-acrylic acid hydrogels incorporated with 5-fluorouracil (5-Fu) and rutin (Ru) for effective anticancer activity with less toxicity. In this study, graft polymerization technique is adopted to formulate hydrogels with various ratios of Zein, acrylic acid, N, N-methylene bisacrylamide, and ammonium persulphate as an initiator. The optimized formulation was identified based on the cross-linking, chemical interactions, intrinsic viscosity (η), dynamic swelling (Q) at pH 1.2, diffusion coefficient (D), solgel fraction (%), and porosity (%). The selected optimized formulation has shown significant improvement in drugs loading and encapsulation efficiency, releasing at pH 1.2 and pH 7.4. Drug release kinetics studies confirmed the controlled release properties of hydrogels. Hydrogels were porous and the drug loading of 5-Fu and Ru was found to be 12.13% and 10.86%, respectively, whereas encapsulation efficiency of 5-Fu and Ru was 89.35% and 81.47%, respectively. Furthermore, form the in vitro cytotoxic screening, it was found that 52.5 µg mL −1 5-Fu and Ru-loaded hydrogel impacted 50% of cell death at 24 h, there by significantly arresting the proliferation of MDA-MB-231 and MCF-7 breast cancer cell lines. Altogether, the optimized pH-responsive hydrogels make them favorable carrier for anticancer drugs for oral delivery.

Molecular mechanisms of anticancer effect of rutin

“…Preparation of oral delivered pH‐responsive Zein‐ co ‐acrylic acid hydrogels in combination with rutin and 5‐fluorouracil (5‐Fu) was carried out by Kunjiappan et al to effectively stimulate anticancer function with lower degrees of toxicity. Optimization of pH‐responsive hydrogels leads to desirable carriers for oral anticancer drugs (Kunjiappan et al, 2019).…”

Influence of Various Model Compounds on the Rheological Properties of Zein-Based Gels

“…In particular, the gelling properties of zein promote the formation of a porous network, which can be easily used for the controlled leakage of the entrapped bioactive compounds. Several studies have described the rheological behavior of specific fractions of zein such as α- and γ-zein dispersions, obtained after the purification of the protein [ 17 , 18 , 19 ], and different materials such as glycerol, β-carotene, acrylic acid, propylene glycol alginate, tannic acid, pea protein, citric acid and acetic anhydride were added to modulate the gelling features of zein [ 20 , 21 , 22 , 23 , 24 , 25 ]. However, our research team recently used commercial zein, at a considerably lower cost than that of the purified form, to prepare gels (up to 20% w / v of protein) without any chemical refinement or the addition of gelling agents; for the first time, the characterization of zein gels was performed under static and dynamic conditions [ 26 ].…”

Targeting Multiple Signaling Pathways in Cancer: The Rutin Therapeutic Approach

“…The anticancer effect was evaluated against MDA-MB-231 and MCF-7 breast cancer cell lines. Rutin and 5-fluorouracil loaded pH-sensitive Zein-co-acrylic acid hydrogels demonstrate a controlled release manner and augment anticancer effects by inducing apoptosis and ROS generation [ 109 ]. Based on these results, pH-sensitive hydrogels may be a suitable formulation for oral delivery of anticancer drugs with the intent of attaining the tumor site-responsive controlled release and thereby decreasing undesirable toxic effects in normal tissues.…”