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This study formulates and optimizes AG-loaded phytosomes (AG-PTMs) by varying l-α-phosphatidylcholine (PC):AG molar ratio and sonication time, yielding a 1:2.7 ratio and 4.9 min processing with 243.7 nm particle size, 0.310 PDI, 72.20% entrapment efficiency, and sustained 24-h release. In HepG2 liver cancer cells, AG-PTMs enhance cellular uptake, suppress proliferation (IC50 4.02 ± 0.14 μM), induce G2-M arrest, and promote mitochondrial-dependent apoptosis via oxidative stress and BAX/BCL2 modulation, increasing caspase-3.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/andrographolide-nanophytosomes-exhibit-enhanced-cellular-delivery-and-pro-apoptotic-activities-in-hepg2-liver-cancer-cells-research-article/383295/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/andrographolide-nanophytosomes-exhibit-enhanced-cellular-delivery-and-pro-apoptotic-activities-in-hepg2-liver-cancer-cells-research-article/383295.png","ImageObject",300,407,{"name":92,"@type":93},"anakgang17","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-25","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":8},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What problem does the study address with andrographolide (AG)?","Question",{"text":112,"@type":113},"AG’s poor solubility and limited cellular permeability restrict its clinical use. The study addresses this by formulating AG into phytosomes for better delivery to cancer cells.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were AG-loaded phytosomes (AG-PTMs) optimized?",{"text":117,"@type":113},"AG-PTMs were optimized by varying the l-α-phosphatidylcholine (PC):AG molar ratio and sonication time as independent variables, resulting in a 1:2.7 AG:PC ratio and 4.9 min sonication.",{"name":119,"@type":110,"acceptedAnswer":120},"What effects do AG-PTMs have on HepG2 liver cancer cells?",{"text":121,"@type":113},"AG-PTMs significantly enhance cellular uptake, repress HepG2 growth (IC50 4.02 ± 0.14 μM), arrest the cell cycle at G2-M, and increase the fraction of apoptotic cells through oxidative stress, mitochondrial dysfunction, and caspase-3 upregulation.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},383295,1790295200,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":8,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},962090883568,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","Drug Delivery  \n2023, vOl. 30, NO. 1, 2174209  \n[https://doi.org/10.1080/10717544.2023.2174209](https://doi.org/10.1080/10717544.2023.2174209)  \nRESEARCH ARTICLE     \nAndrographolide nanophytosomes exhibit enhanced cellular delivery and pro-apoptotic activities in HepG2 liver cancer cells  \nThikryat Neamatallaha, Azizah M. Malebarib, Abdulmohsin J. Alamoudia, Syed Nazreenc, Mohammad Mahboob Alamc, Hawazen H. Bin-Melaihd, Osama A. Abuzinadahd, Shaimaa M. Badr-Eldine,f, Gharam Alhassania, Lamar Makkia and Mohammed Z. Nasrullaha   \naDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz university, Jeddah, Saudi Arabia; bDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz university, Jeddah, Saudi Arabia; cDepartment of Chemistry, Faculty of Science, Albaha university, Albaha, Saudi Arabia; dDepartment of Biological Sciences, Faculty of Sciences, King Abdulaziz university, Jeddah, Saudi Arabia; eDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz university, Jeddah, Saudi Arabia; fDepartment of Pharmaceutics and industrial Pharmacy, Faculty of Pharmacy, Cairo university, Cairo, egypt  \nABSTRACT  \nAndrographolide (AG), a major active constituent of Andrographis paniculata, is known to hinder proliferation of several types of cancer cells. However, its poor solubility and cellular permeability restrict its use in clinical applications. In this study, AG-loaded phytosomes (AG-PTMs) were formulated and optimized with respect to particle size using l-α-phosphatidylcholine (PC):AG ratio and sonication time (ST) as independent variables. The optimized formula was prepared at 1:2.7 for AG:PC molar ratio and 4.9 min for ST and exhibited a particle size of 243.7 ± 7.3 nm, polydispersity index (PDI) of 0.310 and entrapment efficiency of 72.20 ± 4.53. Also, the prepared formula showed a slow release of AG over 24-h period. The antiproliferative activity of AG-PTMs was investigated against the liver cancer cell line HepG2 . AG-PTMs significantly repressed the growth of HepG2 cells with an IC50 value of 4.02 ± 0.14 µM. AG uptake by HepG2 cells was significantly enhanced in incubations containing the optimized formula. AG-PTMs also caused G2-M cell cycle phase arrest and increased the fraction of apoptotic cells in pre-G1 phase. These effects were associated with induction of oxidative stress and mitochondrial dysfunction. In addition, AG-PTMs significantly upregulated mRNA expression of BAX and downregulated that of BCL2. Furthermore, AG-PTMs significantly enhanced the concentration of caspase-3 in comparison to raw AG. These data indicate that the phytosomal delivery of AG significantly inhibited HepG2 cell proliferation through enhanced cellular uptake, arresting cell cycle at the G2-M phase and inducing mitochondrial-dependent apoptosis.  \nARTICLE HISTORY  \nReceived 31 October 2022 Revised 23 January 2023 Accepted 24 January 2023  \nKEYWORDS  \nAndrographolide; phytosomes; HepG2 cells; apoptosis; liver cancer  \n1. Introduction  \nLiver cancer is one of the leading causes of cancer-related mortalities. About 75%–85% of primary liver cancers begin and progress in hepatocytes, which are collectively referred to as hepatocellular carcinoma (K. Wang & Sun, 2018; Sunget al., 2021) . Patients with hepatocellular carcinoma are usually asymptomatic in the early stages as symptoms appear later when the disease advances (Llovet et al., 2008) . Systemic therapies including antiangiogenic antibodies, immune checkpoint inhibitors and tyrosine kinase inhibitors are recommended only at the advanced stages (Cucarull et al., 2022) . Moreover, patients may develop resistance to these treatments or suffer from severe adverse effects (Iavarone et al., 2011; J. Chen et al., 2015; Zhu et al., 2017; Abou-Alfa et al., 2018; Kudo et al., 2018; Lei et al., 2019; Zan et al., 2019) . Therefore, these limitations support the discovery and development of new anticancer therapies.  \nPhytochemicals have been extensi","cbCaiogicy0W7lnb","https://ap.wps.com/l/cbCaiogicy0W7lnb","pdf",1951424,15,"English","# Abstract\n# Introduction","[{\"question\":\"What problem does the study address with andrographolide (AG)?\",\"answer\":\"AG’s poor solubility and limited cellular permeability restrict its clinical use. The study addresses this by formulating AG into phytosomes for better delivery to cancer cells.\"},{\"question\":\"How were AG-loaded phytosomes (AG-PTMs) optimized?\",\"answer\":\"AG-PTMs were optimized by varying the l-α-phosphatidylcholine (PC):AG molar ratio and sonication time as independent variables, resulting in a 1:2.7 AG:PC ratio and 4.9 min sonication.\"},{\"question\":\"What effects do AG-PTMs have on HepG2 liver cancer cells?\",\"answer\":\"AG-PTMs significantly enhance cellular uptake, repress HepG2 growth (IC50 4.02 ± 0.14 μM), arrest the cell cycle at G2-M, and increase the fraction of apoptotic cells through oxidative stress, mitochondrial dysfunction, and caspase-3 upregulation.\"}]","Andrographolide nanophytosomes exhibit enhanced cellular delivery and pro-apoptotic activities in HepG2 liver cancer cells - Research Article | PDF",1790255727,38]