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KMP ethosomes are prepared by the cold method and optimized using Box–Behnken statistical design with three factors: KMP drug concentration, soylecithin content, and ethanol percentage. The optimized formulation is characterized by TEM, DSC, FTIR, in-vitro release, ex-vivo permeation, and storage stability at 4°C/60±5% RH. Results show vesicle size of 283±0.3 nm and zeta potential of −29.67±0.3 mV, with high entrapment efficiency (91.02±0.21%). Optimized ethosomes provide enhanced release (88.2±2.75%) and permeation coefficient (356.25±0.5 μg/cm² over 24 h), supporting targeted prolonged delivery.",{"@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/development-and-optimization-of-kaempferol-loaded-ethosomes-using-boxbehnken-statistical-design-in-vitro-and-ex-vivo-assessments/156119/",{"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/development-and-optimization-of-kaempferol-loaded-ethosomes-using-boxbehnken-statistical-design-in-vitro-and-ex-vivo-assessments/156119.png","ImageObject",300,407,{"name":92,"@type":93},"Oliver","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-06","2026-08-28",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Which variables were used to optimize KMP-loaded ethosomes in the Box–Behnken design?","Question",{"text":112,"@type":113},"Optimization used three factors: KMP drug concentration, soylecithin content, and ethanol percentage. These were varied across three levels in a Box–Behnken statistical design.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How was the optimized formulation evaluated experimentally?",{"text":117,"@type":113},"The optimized KMP ethosomes were examined using TEM, DSC, FTIR spectroscopy, in-vitro release testing, ex-vivo permeation studies, and storage stability assessment at 4°C with controlled humidity.",{"name":119,"@type":110,"acceptedAnswer":120},"What performance improvements did optimized KMP ethosomes show compared with pure KMP?",{"text":121,"@type":113},"Optimized KMP ethosomes achieved higher in-vitro release (88.2±2.75% vs 49.9±1.89%) and higher apparent permeation over 24 h (356.25±0.5 vs 118.46±0.3 μg/cm²). Release kinetics followed the Korsmeyer–Peppas model.","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},156119,1787954039,{"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":44,"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":129,"read_time":36},8796095461610,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","Received: 14 October 2023 Revised: 2 February 2024 Accepted: 19 February 2024  \nDOI: 10.1002/jbm.b.35394  \nRES EARCH A RTICLE  \nDevelopment and optimization of kaempferol loaded ethosomes using Box–Behnken statistical design: In vitro and ex-vivo assessments  \nShraddha Singh Raghav 1 | Bhavna Kumar 1  | Neeraj Kumar Sethiya 1 | Shilpa Pahwa 2  \n1Faculty of Pharmacy, DIT University, Dehradun, Uttarakhand, India  \n2Faculty of Pharmacy, Lloyd Institute of Management and Technology, Greater Noida, Uttar Pradesh, India  \nCorrespondence  \nBhavna Kumar, Faculty of Pharmacy, DIT University, Dehradun, Uttarakhand, India. Email: [bhavna@dituniversity.edu.in](bhavna@dituniversity.edu.in); [bhavnano@gmail.com](bhavnano@gmail.com)  \nAbstract  \nKaempferol (KMP) belong to flavonoid class have developed in ethosomal formulation and were evaluated for their potential to treat diabetic foot ulcers. Even though ethosomes are highly deformable, they can pass through human skin intact. KMP ethosomes were formulated using the cold method and optimized by Box–Behnken design (BBD) (three-factor, three-level (33)). The formulation variables used for optimization are drug concentration of KMP, soylecithin content, and ethanol percentage. The optimized formulation was examined using transmission electronic microscopy (TEM), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, in-vitro release, ex-vivo permeation studies, and storage stability. The optimized KMPethosomes was found to have vesicle size (VS) of 283 ± 0.3 nm and zeta potential (ZP) of 􀀁29. 67 ± 0 .3 mV, polydispersity index (PDI) of 0 .36,% entrapment efficiency (%EE) of 91.02 ± 0.21%, drug loading (%) of 46.23 ± 2.5% followed by good storage stability at 4􀀃 C/60 ± 5% RH. In vitro drug release of optimized KMP ethosomes was 88.2 ± 2.75%, which was approximately double when compared with pure KMP release, that is 49.9 ± 1 .89% . The release kinetics for optimized KMP ethosomes follows the Korsmeyer–Peppas model. An apparent permeation coefficient of 356 .25 ± 0.5 μg/cm2 was determined and compared with pure KMP (118.46 ± 0 .3 μg/cm2) for 24 h. According to the study, ethosomes can be a cutting-edge strategy that offers a new delivery method for prolonged and targeted distribution of KMP in a variety of dosage forms including oral, topical, transdermal, and so forth.  \nKEYWOR DS  \nBox–Behnken design expert tool, diabetic foot ulcer, ethosomes, in-vitro and ex-vivo study, kaempferol  \n1 | INTRODUCTION  \nA diabetic foot ulcer (DFU), can have detrimental effects on both mental and physical health for those suffering from diabetes.1 Untreated DFUs can result in lower limb amputations. DFUs are the leading cause of nontraumatic leg amputations. Various studies have suggested a prevalence of 1.3%–12% for DFUs, and 1.5%–7% for  \ndiabetic foot amputations. There are many factors responsible for DFU, including neuropathy, peripheral artery disease, biochemical imbalances, and impaired wound healing. Apart from amputation of a lower limb, DFU can cause infection and even death. The effects of diabetes delay wound healing by impairing the phases of wound recovery, that is, hemostasis, inflammation, proliferation, and remodeling. The main features of diabetic wound restoration include  \nJ Biomed Mater Res. 2024;112:e35394 .  \n[https://doi.org/10.1002/jbm.b.35394](https://doi.org/10.1002/jbm.b.35394)  \n[wileyonlinelibrary.com/journal/jbmb](wileyonlinelibrary.com/journal/jbmb)  \n© 2024 Wiley Periodicals LLC.  \n1 of 16  \n2 of 16  \n  RAGHAV ET AL.  \npersistent anti-inflammatory phases, poor granulation tissue formation, impaired angiogenesis, and poor wound tensile strength. In the management of DFU, multidisciplinary approaches are used. In order to manage the condition, it is necessary to classify the stage and severity of the condition, control diabetes mellitus, treat infections, and improve blood flow. The DFU treatment focuses on improving perfusion, reducing pressur","cbCaicxpptAmDgSv","https://ap.wps.com/l/cbCaicxpptAmDgSv","pdf",27196008,16,"English","# Introduction\n## Diabetic foot ulcer background and treatment challenges\n## Rationale for phytomedicines and KMP\n# Formulation and Optimization\n## KMP ethosome preparation\n## Box–Behnken statistical design variables\n# Characterization and Evaluation\n## Physicochemical characterization (TEM, DSC, FTIR)\n## In-vitro release\n## Ex-vivo permeation\n## Storage stability\n# Results and Discussion\n## Optimized formulation performance\n## Release kinetics and permeation comparison\n# Conclusion","[{\"question\":\"Which variables were used to optimize KMP-loaded ethosomes in the Box–Behnken design?\",\"answer\":\"Optimization used three factors: KMP drug concentration, soylecithin content, and ethanol percentage. These were varied across three levels in a Box–Behnken statistical design.\"},{\"question\":\"How was the optimized formulation evaluated experimentally?\",\"answer\":\"The optimized KMP ethosomes were examined using TEM, DSC, FTIR spectroscopy, in-vitro release testing, ex-vivo permeation studies, and storage stability assessment at 4°C with controlled humidity.\"},{\"question\":\"What performance improvements did optimized KMP ethosomes show compared with pure KMP?\",\"answer\":\"Optimized KMP ethosomes achieved higher in-vitro release (88.2±2.75% vs 49.9±1.89%) and higher apparent permeation over 24 h (356.25±0.5 vs 118.46±0.3 μg/cm²). Release kinetics followed the Korsmeyer–Peppas model.\"}]","Development and optimization of kaempferol loaded ethosomes using Box–Behnken statistical design - In vitro and ex-vivo assessments | PDF"]