Mulukuri N V L Sirisha, Dhara Moumita, Gupta Dheeraj, Devi Kusum, Kumar Pankaj
Department of Pharmaceutical Chemistry, NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Nitte (Deemed to be University), Mangalore 575018, India.
Nitte College of Pharmaceutical Sciences, Bangalore 560064, India.
Gels. 2023 Jun 21;9(7):507. doi: 10.3390/gels9070507.
An epidermoid carcinoma is a form of non-melanoma skin cancer that originates from the outer layer of the skin's squamous cells. Previous studies have shown that andrographis extract and andrographolide inhibit the growth and proliferation of epidermoid carcinoma cells while also inducing cell cycle arrest and apoptosis. The objective of this study was to improve the anticancer efficacy of the andrographolide-rich extract by delivering it in the form of nanoemulgel. During the formulation of emulgels, sonication, and homogenization were employed, and a 2-factorial design was used to optimize the formulations through the quality by design (QbD) approach. The optimized formulation (AEE8) was subjected to preliminary evaluations along with particle size, drug release, and scanning electron microscopy (SEM) studies. The potential of the optimized emulgel against A431 cell lines was also investigated using MTT assay followed by flow cytometric analysis. The SEM results reveal that the optimized emulgel had a well-defined spherical shape, with a droplet size of 226 ± 1.8 nm, a negative surface charge of -30.1 ± 1.6 mV, and a PDI of 0.157. The cellular data indicate that AEE8 reduced the viability of the A431 cells with an IC of 16.56 μg/mL, as determined by MTT assay when compared to cells treated with the extract alone. Furthermore, the flow cytometric analysis of the optimized emulgel formulation demonstrated a marked G2/M phase arrest. This finding further supports the effectiveness of the gel in disrupting the cell cycle at the critical G2 and M phases, which are pivotal for cell division and proliferation. This disruption in cell cycle progression can impede the growth and spread of cancer cells, making the gel a promising candidate for anti-skin-cancer therapy. The safety of emulgels (AEE8) was validated through rigorous biocompatibility testing conducted on HDF (human dermal fibroblast) cell lines, ensuring their suitability for use. Considering the potential of the nanoemulgel, particularly AEE8, as demonstrated by its favorable properties and its ability to disrupt the cell cycle, it holds great promise as an innovative approach to treating skin cancer.
表皮样癌是一种非黑色素瘤皮肤癌，起源于皮肤鳞状细胞的外层。先前的研究表明，穿心莲提取物和穿心莲内酯可抑制表皮样癌细胞的生长和增殖，同时还能诱导细胞周期停滞和凋亡。本研究的目的是以纳米乳凝胶的形式递送富含穿心莲内酯的提取物，以提高其抗癌效果。在制备乳凝胶的过程中，采用了超声处理和均质化，并采用二因素设计通过质量源于设计（QbD）方法优化配方。对优化后的配方（AEE8）进行了粒度、药物释放和扫描电子显微镜（SEM）研究等初步评估。还使用MTT法，随后进行流式细胞术分析，研究了优化后的乳凝胶对A431细胞系的作用潜力。SEM结果显示，优化后的乳凝胶具有明确的球形，液滴尺寸为226±1.8nm，表面负电荷为-30.1±1.6mV，多分散指数（PDI）为0.157。细胞数据表明，与单独用提取物处理的细胞相比，通过MTT法测定，AEE8以16.56μg/mL的半数抑制浓度（IC）降低了A431细胞的活力。此外，对优化后的乳凝胶配方进行的流式细胞术分析显示出明显的G2/M期停滞。这一发现进一步支持了该凝胶在关键的G2和M期破坏细胞周期的有效性，而这两个时期对细胞分裂和增殖至关重要。细胞周期进程的这种破坏会阻碍癌细胞的生长和扩散，使该凝胶成为抗皮肤癌治疗的有希望的候选药物。通过对人皮肤成纤维细胞（HDF）细胞系进行严格的生物相容性测试，验证了乳凝胶（AEE8）的安全性，确保了它们的适用性。鉴于纳米乳凝胶，特别是AEE8的潜力，如其良好的性能及其破坏细胞周期的能力所证明的那样，它作为一种治疗皮肤癌的创新方法具有很大的前景。
