Development and Optimization of Novel Emulgel Loaded with Andrographolide-Rich Extract and Sesame Oil Using Quality by Design Approach: In Silico and In Vitro Cytotoxic Evaluation against A431 Cells
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...
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MDPI AG
2023-06-01
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| Series: | Gels |
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| author | N. V. L. Sirisha Mulukuri Moumita Dhara Dheeraj Gupta Kusum Devi Pankaj Kumar |
| author_facet | N. V. L. Sirisha Mulukuri Moumita Dhara Dheeraj Gupta Kusum Devi Pankaj Kumar |
| author_sort | N. V. L. Sirisha Mulukuri |
| collection | DOAJ |
| description | 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<sup>2</sup>-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<sub>50</sub> 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. |
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| issn | 2310-2861 |
| language | English |
| last_indexed | 2024-03-11T01:03:59Z |
| publishDate | 2023-06-01 |
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| spelling | doaj.art-b6c4ee86a27642eea6450dd193bf37d12023-11-18T19:27:04ZengMDPI AGGels2310-28612023-06-019750710.3390/gels9070507Development and Optimization of Novel Emulgel Loaded with Andrographolide-Rich Extract and Sesame Oil Using Quality by Design Approach: In Silico and In Vitro Cytotoxic Evaluation against A431 CellsN. V. L. Sirisha Mulukuri0Moumita Dhara1Dheeraj Gupta2Kusum Devi3Pankaj Kumar4Department of Pharmaceutical Chemistry, NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Nitte (Deemed to be University), Mangalore 575018, IndiaNitte College of Pharmaceutical Sciences, Bangalore 560064, IndiaDepartment of Pharmaceutical Chemistry, NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Nitte (Deemed to be University), Mangalore 575018, IndiaNitte College of Pharmaceutical Sciences, Bangalore 560064, IndiaDepartment of Pharmaceutical Chemistry, NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Nitte (Deemed to be University), Mangalore 575018, IndiaAn 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<sup>2</sup>-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<sub>50</sub> 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.https://www.mdpi.com/2310-2861/9/7/507<i>Andrographis paniculata</i>anticanceremulgelsnon-melanomatopical |
| spellingShingle | N. V. L. Sirisha Mulukuri Moumita Dhara Dheeraj Gupta Kusum Devi Pankaj Kumar Development and Optimization of Novel Emulgel Loaded with Andrographolide-Rich Extract and Sesame Oil Using Quality by Design Approach: In Silico and In Vitro Cytotoxic Evaluation against A431 Cells Gels <i>Andrographis paniculata</i> anticancer emulgels non-melanoma topical |
| title | Development and Optimization of Novel Emulgel Loaded with Andrographolide-Rich Extract and Sesame Oil Using Quality by Design Approach: In Silico and In Vitro Cytotoxic Evaluation against A431 Cells |
| title_full | Development and Optimization of Novel Emulgel Loaded with Andrographolide-Rich Extract and Sesame Oil Using Quality by Design Approach: In Silico and In Vitro Cytotoxic Evaluation against A431 Cells |
| title_fullStr | Development and Optimization of Novel Emulgel Loaded with Andrographolide-Rich Extract and Sesame Oil Using Quality by Design Approach: In Silico and In Vitro Cytotoxic Evaluation against A431 Cells |
| title_full_unstemmed | Development and Optimization of Novel Emulgel Loaded with Andrographolide-Rich Extract and Sesame Oil Using Quality by Design Approach: In Silico and In Vitro Cytotoxic Evaluation against A431 Cells |
| title_short | Development and Optimization of Novel Emulgel Loaded with Andrographolide-Rich Extract and Sesame Oil Using Quality by Design Approach: In Silico and In Vitro Cytotoxic Evaluation against A431 Cells |
| title_sort | development and optimization of novel emulgel loaded with andrographolide rich extract and sesame oil using quality by design approach in silico and in vitro cytotoxic evaluation against a431 cells |
| topic | <i>Andrographis paniculata</i> anticancer emulgels non-melanoma topical |
| url | https://www.mdpi.com/2310-2861/9/7/507 |
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