Thermosensitive Hydrogels Loaded with Resveratrol Nanoemulsion: Formulation Optimization by Central Composite Design and Evaluation in MCF-7 Human Breast Cancer Cell Lines

Abstract

The second most common cause of mortality among women is breast cancer. A variety of natural compounds have been demonstrated to be beneficial in the management of various malignancies. Resveratrol is a promising anticancer polyphenolic compound found in grapes, berries, etc. Nevertheless, its low solubility, and hence its low bioavailability, restrict its therapeutic potential. Therefore, in our study, we developed a thermosensitive hydrogel formulation loaded with resveratrol nanoemulsion to enhance its bioavailability. Initially, resveratrol nanoemulsions were formulated and optimized utilizing a central composite-face-centered design. The independent variables for optimization were surfactant level, homogenization speed, and time, while the size and zeta potential were the dependent variables. The optimized nanoemulsion formulation was converted into a sensitive hydrogel using poloxamer 407. Rheological studies proved the formation of gel consistency at physiological temperature. Drug loading efficiency and in vitro drug release from gels were also analyzed. The drug release mechanisms from the gels were assessed using various mathematical models. The effect of the optimized thermosensitive resveratrol nanoemulsion hydrogel on the viability of human breast cancer cells was tested using MCF-7 cancer cell lines. The globule size of the selected formulation was 111.54 ± 4.16 nm, with a zeta potential of 40.96 ± 3.1 mV. Within 6 h, the in vitro release profile demonstrated a release rate of 80%. According to cell line studies, the produced hydrogel of resveratrol nanoemulsion was cytotoxic to breast cancer cells. Overall, the results proved the developed nanoemulsion-loaded thermosensitive hydrogel is a promising platform for the effective delivery of resveratrol for the management of breast cancer.

Formulation, Optimization and Evaluation of Cytarabine-Loaded Iron Oxide Nanoparticles: From In Vitro to In Vivo Evaluation of Anticancer Activity

“…After 72 h, 20 mL of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) solution of concentration (10 µg/mL) was added to each well. These plates were centrifuged for 25 min at 3000 rpm after being incubated at 37 °C in a CO2 incubator for 4 h. After the formazan crystals had been treated with DMSO, the absorbance of each well was measured at 570 nm using an ELISA reader at 25 °C (100 mL) [ 30 , 31 ].…”

Therapeutic Implications of Dietary Polyphenols-Loaded Nanoemulsions in Cancer Therapy

“…The NE inhibited the pancreatic cancer cells (BxPC-3) by down-regulating cyclin A, cyclin B, CDK1, and CDK2 expressions and up-regulating p53 and p21 expressions, leading to cellular apoptosis. 134 Kotta et al 135 developed RVT-loaded thermosensitive hydrogels for effective delivery of RVT against breast cancertherapy, as it exhibited cytotoxic effects on breast cancer cells. 135 Furthermore, few specific findings of anticancer effects and associated mechanism of polyphenols-loaded NEs against various cancer types is tabulated in Table 1, and the preclinical/clinical evidence of various polyphenols-loaded NEs have been enlisted in Table 2.…”

Injectable Poloxamer Hydrogels for Local Cancer Therapy

“…Then, the obtained poloxamer dispersions are usually characterized regarding sol-gel transition, rheological properties, in vitro degradation, and release profile. The rich phase behavior of poloxamer dispersions makes them a versatile platform for drug delivery in the form of micelles or hydrogels, which have enduring popularity in cancer therapy [19][20][21]. However, before considering the development of pure poloxamer hydrogels, researchers should be aware of their limitations under high compression or in aqueous media due to low mechanical strength and fast erosion, respectively [22].…”