Polyvinyl Alcohol (PVA)-Based Nanoniosome for Enhanced in vitro Delivery and Anticancer Activity of Thymol.

Introduction: There is an unmet need to develop potent therapeutics against cancer with minimal side effects and systemic toxicity. Thymol (TH) is an herbal medicine with anti-cancer properties that has been investigated scientifically. This study shows that TH induces apoptosis in cancerous cell lines such as MCF-7, AGS, and HepG2. Furthermore, this study reveals that TH can be encapsulated in a Polyvinyl alcohol (PVA)-coated niosome (Nio-TH/PVA) to enhance its stability and enable its controlled release as a model drug in the cancerous region. Materials and Methods: TH-loaded niosome (Nio-TH) was fabricated and optimized using Box-Behnken method and the size, polydispersity index (PDI) and entrapment efficiency (EE) were characterized by employing DLS, TEM and SEM, respectively. Additionally, in vitro drug release and kinetic studies were performed. Cytotoxicity, antiproliferative activity, and the mechanism were assessed by MTT assay, quantitative real-time PCR, flow cytometry, cell cycle, caspase activity evaluation, reactive oxygen species investigation, and cell migration assays. Results: This study demonstrated the exceptional stability of Nio-TH/PVA at 4 °C for two months and its pH-dependent release profile. It also showed its high toxicity on cancerous cell lines and high compatibility with HFF cells. It revealed the modulation of Caspase-3/Caspase-9, MMP-2/MMP-9 and Cyclin D/ Cyclin E genes by Nio-TH/PVA on the studied cell lines. It confirmed the induction of apoptosis by Nio-TH/PVA in flow cytometry, caspase activity, ROS level, and DAPI staining assays. It also verified the inhibition of metastasis by Nio-TH/PVA in migration assays. Conclusion: Overall, the results of this study revealed that Nio-TH/PVA may effectively transport hydrophobic drugs to cancer cells with a controlled-release profile to induce apoptosis while exhibiting no detectable side effects due to their biocompatibility with normal cells.

3D-printing-assisted synthesis of paclitaxel-loaded niosomes functionalized by cross-linked gelatin/alginate composite: Large-scale synthesis and in-vitro anti-cancer evaluation.

Breast cancer is one of the most lethal cancers, especially in women. Despite many efforts, side effects of anti-cancer drugs and metastasis are still the main challenges in breast cancer treatment. Recently, advanced technologies such as 3D-printing and nanotechnology have created new horizons in cancer treatment. In this work, we report an advanced drug delivery system based on 3D-printed gelatin-alginate scaffolds containing paclitaxel-loaded niosomes (Nio-PTX@GT-AL). The morphology, drug release, degradation, cellular uptake, flow cytometry, cell cytotoxicity, migration, gene expression, and caspase activity of scaffolds, and control samples (Nio-PTX, and Free-PTX) were investigated. Results demonstrated that synthesized niosomes had spherical-like, in the range of 60-80 nm with desirable cellular uptake. Nio-PTX@GT-AL and Nio-PTX had a sustained drug release and were biodegradable. Cytotoxicity studies revealed that the designed Nio-PTX@GT-AL scaffold had <5 % cytotoxicity against non-tumorigenic breast cell line (MCF-10A) but showed 80 % cytotoxicity against breast cancer cells (MCF-7), which was considerably more than the anti-cancer effects of control samples. In migration evaluation (scratch-assay), approximately 70 % reduction of covered surface area was observed. The anticancer effect of the designed nanocarrier could be attributed to gene expression regulation, where a significant increase in the expression and activity of genes promoting apoptosis (CASP-3, CASP-8, and CASP-9) and inhibiting metastasis (Bax, and p53) and a remarkable decrease in metastasis-enhancing genes (Bcl2, MMP-2, and MMP-9) were observed. Also, flow cytometry results declared that Nio-PTX@GT-AL reduced necrosis and increased apoptosis considerably. The results of this study prove that employing 3D-printing and niosomal formulation is an effective approach in designing nanocarriers for efficient drug delivery applications.