Andrographolide is a natural diterpene lactone with multiple biological effects. In the present study, a total of 11 andrographolide-loaded emulgels (ANG 1- ANG 11) were prepared by emulsification and solvent evaporation method using flaxseed oil and xanthan gum in different ratios, as suggested by the Design-Expert software. A 2-factor-5-level design was employed with different responses including spreadability, extrudability, viscosity, and drug release after 1 h (h) and 24 h. Based on the Design-Expert software response, the optimized emulgel ANG 12 was formulated and evaluated. The 24 h In-vitro drug release was found to be 95.7 % following Higuchi kinetics. Ex-vivo skin retention of 784.78 ug/cm² was observed during the study. MTT assay performed on Human epidermoid carcinoma (A-431) cells demonstrated cell growth arrest at G0/G1 and G2/M phase after 24 h of ANG 12 treatment (IC₅₀: 11.5 µg/ml). The cellular permeability of ANG-12 was assessed by Fluorescein isothiocyanate (FITC) assay. Compared to untreated cells (0.54 % uptake) the ANG-12 treated cells had shown 87.17 % FITC permeation. The biocompatibility study performed on non-cancerous human dermal fibroblast cells (HDF cells) shows 91.54 % viability after 24 h of the treatment showing the non-toxic nature of ANG-12. Confocal imaging had shown a significant time-dependent increase in in-vivo cellular uptake with enhanced, progressive penetration of the emulgel into the skin. An in-vivo skin irritation study conducted on Swiss albino mice confirmed the safety aspects of the ANG 12. Hence, it can be concluded that nanoemulgel of andrographolide (ANG 12) could be a novel approach to treating skin cancer.

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 2²-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 IC₅₀ 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.

This study emphasizes overcoming the challenges of targeted drug delivery in colon cancer therapy by developing gastrointestinal (GI) stable, pectin-coated nanoliposomes for the oral delivery of Apigenin-Cyclodextrin Complex as an in situ gel formation. Initially, the formulation was strategically designed using design expert software for formulation optimization. FTIR and XRD studies were conducted to ensure physical compatibility and to confirm the encapsulation of apigenin within the formulation. In process optimization, among all seventeen formulations run tested, PNL (Api-Cy)-13 was identified for the highest drug loading, favourable size dimension of particle with zeta potential, and spherical external morphology through SEM analysis. The metered drug release during an in vitro study for PNL (Api-Cy)-13 was remarkably high (more than 75% of drug availability in the colonic environment, precisely in contrast to only 20% in the gastric phase in a sustained release manner), focused on colon drug targeting as an in situ gel. Furthermore, apigenin release from PNL (Api-Cy)-13 in an ex vivo chick ileum permeability study was observed both in the absence and presence of 1% vancomycin. An incremental apigenin release in the absence of the antibiotic (1% vancomycin) indicated gut microbial-associated and pectinase-mediated drug release. Here, pectin degradation materializes by the colonic microbial environment, which facilitates desirable incremental colonic drug permeation. Finally, an in vitro MTT assay and a competitive flowcytometric cell uptake study with PNL (Api-Cy)-13 using HCT-116 cells proved significant superiority in cytotoxicity profile for apigenin when delivered as an optimized coated nanoliposome in comparison to free apigenin or other non-modified nano-formulation. Also, the inhibition of the cell efflux process was validated by Multidrug Resistance 1 (MDR1) gene regulation. These observations establish an undoubted promise for the novel biopolymer, pectin-based apigenin-cyclodextrin nanoliposomes as targeted therapy in colon cancer with significant in vivo pharmacokinetics and safety profile.