Development, Optimization, and In Vitro Evaluation of Novel Oral Long-Acting Resveratrol Nanocomposite In-Situ Gelling Film in the Treatment of Colorectal Cancer

Abstract

This study aimed to develop and evaluate sustained-release (SR) long-acting oral nanocomposites in-situ gelling films of resveratrol (Rv) to treat colorectal cancer. In these formulations, Rv-Soy protein (Rv-Sp) wet granules were prepared by the kneading method and then encapsulated in the sodium alginate (NA) dry films. The prepared nanocomposite in-situ gels films were characterized using dynamic light scattering, Fourier-transform infrared spectroscopy, X-ray diffraction, and scanning electron microscopy. The optimized formulations were further evaluated based on drug encapsulation efficiency, pH-drug release profile, swelling study, and storage time effects. The optimized formulation was tested for its anticancer activity against colorectal cancer cells using the cytotoxicity assessment, apoptosis testing, cell cycle analysis, gene expression analysis, and protein estimation by the reverse-transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay methods, respectively. The optimum film showed encapsulation efficiency of 97.87% ± 0.51 and drug release of 14.45% ± 0.043 after 8 h. All physiochemical characterizations confirmed, reasoned, and supported the drug release experiment’s findings and the encapsulation assay. The Rv nanocomposite formulation showed concentration-dependent cytotoxicity enhanced apoptotic activity as compared to free Rv (p < 0.05). In addition, Rv nanocomposite formulation caused a significant increase in Bcl-2-associated protein X (Bax) and a decrease in expression of B-cell lymphoma 2, interleukin 1 beta, IL-6, and tumor necrosis factor-alpha (Bcl2, IL-1β, IL-6, and TNF-α respectively) compared to that of free Rv in HCT-116 cells. These results suggest that long-acting Rv nanocomposite gels could be a promising agent for colorectal cancer treatment.

Development and Evaluation of Ginkgo biloba/Sodium Alginate Nanocomplex Gel as a Long-Acting Formulation for Wound Healing

“…On the other hand, the FTIR spectra of nanocomplex gel in Figure 1 , i.e., NG, exhibited dissipation of characteristic peaks from 3200 to 3600 cm −1 , which suggested hydrogen bonding between the OH and CH 2 group. In addition, the NG spectrum showed lower peaks intensity of 1694, 1646, and 1068 cm −1 to support the assumption of the encapsulation of carboxylate and hydroxyl groups in the NG core [ 15 , 17 ].…”

“…The alginate and ginkgo extract hydroxyl and carboxylate groups initiated hydrophilic and hydrogen bond interactions in the core of the nanocomplex gel, leaving the outer surfaces of the nanohydrogel neutral. This result was supported in the FTIR characterization of the NG interactions and surface functional groups [ 14 , 15 ]. After all, the optimum nanocomplex gel encapsulation efficiency was 91 ± 1.8%.…”

“…Interestingly, the optimum nanocomplex gel swelling and diffusibility ratio differences between 5, 6, 7, and 8 h were less than the differences in swelling between the earlier time intervals, indicating a plateau swelling stage [ 18 ]. Generally, the swelling profile could be correlated to the water solubilization of the alginate and ginkgo glycosides [ 15 , 17 ]. On the other hand, the plateau stage might indicate that the swelling of the nanogel had a certain extent, and the alginate and ginkgo nanogel preserved a specific resilience degree [ 15 , 17 ].…”

“…Generally, the swelling profile could be correlated to the water solubilization of the alginate and ginkgo glycosides [ 15 , 17 ]. On the other hand, the plateau stage might indicate that the swelling of the nanogel had a certain extent, and the alginate and ginkgo nanogel preserved a specific resilience degree [ 15 , 17 ].…”

Electrospun Coaxial Fibers to Optimize the Release of Poorly Water-Soluble Drug

“…More than two-thirds of promising drugs on the market have limited biomedical functions due to dissolution problems [ 6 , 7 , 8 ]. Thus, many drug delivery systems are exploited to improve the bioavailability of poorly soluble drugs, such as nanoparticles [ 9 , 10 , 11 , 12 , 13 ], hydrogels [ 14 , 15 ], 3D printing [ 16 , 17 ], electrospun fibers [ 18 , 19 , 20 , 21 ], nanocapsules [ 22 ], and microspheres [ 23 ]. Among many drug delivery systems, electrospinning, a “one-step” process with cheap raw materials, shows remarkable potential in the delivery of poorly soluble drugs in recent studies.…”