CCD-optimized Moringa oleifera-based hydrogel for the targeted and controlled release of the anti-cancer drug Raloxifene: evaluation of hemocompatible, cytotoxic and antioxidant properties

Abstract

Raloxifene, a benzothiophene derivative, was approved for the treatment of breast cancer in 2007 by the U.S. Food and Drug Administration. Herein, we designed a statistically optimized drumstick tree extracted Moringa oleifera gum-based hydrogel for the targeted and controlled release of Raloxifene to overcome the problem of its poor bioavailability and dissolution rate. The synthesized hydrogel was characterized using XRD, FE-SEM, FTIR, H¹-NMR, TGA, and rheology measurements, and release experiments were conducted at three different pH levels, with the results analyzed in a UV-visible spectrophotometer at 290 nm. It was noted that the maximum amount of drug release took place at pH 4 (824.88 ± 18.236 ppm), followed by pH 6.8 (589.873 ± 30.056 ppm), and the least at pH 7.4 (323.952 ± 30.431 ppm) due to the breakage of hydrogen bonding at acidic pH. It was found that pH was the key criterion behind drug release, as the swelling rate was proportional to drug release, explaining the reason behind maximum release happening at acidic pH and minimum at basic pH. Furthermore, the hydrogel also possessed anti-oxidant properties, exhibiting 85.092% activity at the highest concentration. The hemolytic assay proved the hydrogel to be non-hemolytic, showing less than 12% hemolysis at a maximum 512 μg ml⁻¹ concentration. Cytocompatibility assay using the Hct cell line exhibited no toxicity to the cells up to 5 μg ml⁻¹. Therefore, the prepared MO-g-poly(AA) proves to be an excellent biocompatible matrix for the pH-dependent release of Raloxifene, making it available in the system in an optimal amount for 65 hours.