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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.

Abstract Prostate cancer (PCa) is one of the fatal illnesses among males globally. PCa-treatment does not include radiotherapy. Chemotherapy eventually causes drug resistance, disease recurrence, metastatic advancement, multi-organ failure, and death. Preclinical data on PCa-induced by carcinogens are truly scarce. Although some data on xenograft-PCa in animals are available, they mostly belonged to immuno-compromised animals. Here, we developed ΔPSap4#5 aptamer surface-functionalized abiraterone-loaded biodegradable nanoparticle (Apt-ABR-NP) to investigate its targeting ability to prostate-specific membrane antigen (PSMA) in carcinogen-induced PCa mice and the therapeutic efficacy of the formulation. Aptamers are called synthetic monoclonal antibodies for their target specificity. However, they are devoid of the toxicity problem generally associated with the antibody. Abiraterone is a testosterone and androgen inhibitor, a new drug molecule that shows good therapeutic efficacy in PCa. The developed nanoparticles were physicochemically characterized and used for various in vitro and in vivo investigations. Nanoparticles had an average size of 149 nm with sustained drug release that followed Korsmeyer–Peppas kinetics. In vitro investigation showed that Apt-ABR-NP produced 87.4% apoptotic cells and 95.3% loss of mitochondrial membrane potential in LNCaP cells after 48 h of incubation. In vivo gamma scintigraphy, live imaging, and biodistribution studies in prostate cancer animal models showed the predominant targeting potential of Apt-ABR-NP. Histopathological investigation showed the remarkable therapeutic efficacy of the formulation. The pharmacokinetic study showed an increased biological half-life and enhanced blood residence time of Apt-ABR-NP. Apt-ABR-NP therapy can thus minimize off-target cytotoxicity, reduce drug loss due to site-specific delivery, and deliver abiraterone in a sustained manner to the organ of interest. Thus, the present study brings new hope for better therapeutic management of PCa in the near future. Graphical Abstract

Abstract Hepatocellular carcinoma (HCC) is a leading cause of death globally. Even though the progressive invention of some very potent therapeutics has been seen, the success is limited due to the chemotherapeutic resistance and recurrence in HCC. Advanced targeted treatment options like immunotherapy, molecular therapy or surface-engineered nanotherapeutics could offer the benefits here owing to drug resistance over tumor heterogenicity. We have developed tumor-sensing phosphorothioate and amino-modified aptamer (AS1411)-conjugated stealth nanoliposomes, encapsulating with apigenin for precise and significant biodistribution of apigenin into the target tumor to exploit maximum bio-therapeutic assistances. The stable aptamer functionalized PEGylated nanoliposomes (Apt-NLCs) had an average vesicle size of 100–150 nm, a smooth surface, and an intact lamellarity, as ensured by DLS, FESEM, AFM, and Cryo-TEM. This study has specified in vitro process of optimum drug (apigenin) extrusion into the cancer cells by nucleolin receptor-mediated cellular internalization when delivered through modified AS1411 functionalized PEGylated nanoliposomes and ensured irreversible DNA damage in HCC. Significant improvement in cancer cell apoptosis in animal models, due to reduced clearance and higher intratumor drug accumulation along with almost nominal toxic effect in liver, strongly supports the therapeutic potential of aptamer-conjugated PEGylated nanoliposomes compared to the nonconjugated formulations in HCC. The study has established a robust superiority of modified AS1411 functionalized PEGylated nanoliposomes as an alternative drug delivery approach with momentous reduction of HCC tumor incidences. Graphical Abstract

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.