[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-450279-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-450279-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","comparative-human-and-porcine-skin-permeation-profiles-of-novel-metformin-lotion-formulations","Comparative human and porcine skin permeation profiles of novel metformin lotion formulations","","Metformin (Met), a highly hydrophilic antidiabetic drug, has limited passive diffusion through the stratum corneum, motivating optimized formulations for transdermal delivery. This study compared Met permeability in human and porcine ear skin using three lotion formulations with distinct permeation enhancers: Gly alone, Gly+propylene glycol (PG), and PG+Transcutol®. Human skin showed minimal permeation for Gly and PG, while PG+Transcutol® greatly increased cumulative permeation and flux. Porcine skin exhibited higher permeability for all formulations, potentially overestimating human delivery for hydrophilic drugs, yet both Gly- and PG-based lotions produced measurable skin accumulation for topical relevance.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & 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is metformin difficult to deliver through the skin?","Question",{"text":63,"@type":64},"Metformin is highly hydrophilic and extremely polar, which restricts passive diffusion through the stratum corneum and limits transdermal delivery without specialized formulations.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"Which lotion formulation produced the greatest permeation in human skin?",{"text":68,"@type":64},"The formulation containing PG and Transcutol® (PG + T) markedly increased cumulative permeation and flux, while glycerol (Gly) and PG alone showed minimal permeation.",{"name":70,"@type":61,"acceptedAnswer":71},"How did porcine skin permeability compare with human skin in this study?",{"text":72,"@type":64},"Porcine skin showed consistently higher permeability across all formulations (Gly \u003C PG \u003C PG+T), suggesting it may overestimate human permeability for hydrophilic 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nature.com/scientificreports)  \nOPEN  \nComparative human and porcine skin permeation profiles of novel metformin lotion formulations  \nCelina Zhao1, Jianying Zhang1, Vasyl Pastukh1, Asim Ejaz2 & James H-C. Wang1,3,4􀀍  \nMetformin (Met), a highly hydrophilic drug, exhibits anti-inflammatory and regenerative effects beyond its antidiabetic role. However, its extreme polarity limits passive diffusion through the stratum corneum, necessitating optimized formulations for effective transdermal delivery. This study compared Met permeability through human and porcine ear skin using three lotion formulations containing different permeation enhancers: (1) 6% Met + glycerol (Gly); (2) 6% Met+ Gly and propylene glycol (PG); and (3) 10% Met + PG and Transcutol® (PG +T). In human skin, Gly and PG formulations showed minimal permeation, whereas PG +T markedly increased cumulative permeation and flux, confirming the critical role of Transcutol®. Porcine skin displayed consistently higher permeability across all formulations (Gly \u003C PG\u003C PG+T), indicating that it may overestimate human permeability to hydrophilic drugs. Despite limited transdermal flux, Gly-and PG-based lotions produced measurable Met accumulation within the epidermis and dermis, suggesting potential for topical use. Overall, these results emphasize the importance of enhancer selection—particularly Transcutol®—in improving dermal delivery of hydrophilic compounds and caution against relying solely on porcine skin as a human surrogate.  \nKeywords Metformin, Lotion, Human skin, Porcine skin, Permeation, Enhancer  \nThe human skin, the body’s largest organ, serves as a vital barrier against the external environment and plays key physiological roles such as thermoregulation and sensory perception. Structurally, it consists of three primary layers: the epidermis, dermis, and hypodermis. The outermost epidermis contains the stratum corneum, an extremely thin but highly dense layer composed of hydrophobic, protein-rich corneocytes embedded in a lipid matrix1. This “brick-and-mortar” structure functions as the body’s first line of defense against environmental threats, prevents water loss, and strictly regulates the permeation of external substances. Consequently, the stratum corneum presents a major obstacle to transdermal drug delivery systems (TDDS)2.  \nDespite this formidable barrier, TDDS offer a non-invasive alternative to oral or injectable routes, with advantages such as sustained drug release, improved patient compliance, and avoidance of first-pass metabolism. The large and accessible surface area of the skin further supports its utility for therapeutic applications2. Evaluating skin permeation is therefore critical in developing effective TDDS, requiring consideration of drug physicochemical properties (lipophilicity, molecular size, solubility, ionization), formulation strategies, selection of skin models, and methods for permeation assessment3.  \nMetformin (Met), an FDA-approved first-line oral antidiabetic drug, has recently drawn attention for topical and transdermal applications beyond glucose control. Incorporating metformin into topical formulations can minimize gastrointestinal side effects and expand its therapeutic potential to local tissues4,5. However, the extreme hydrophilicity and zwitterionic nature of metformin (logP ≈ − 2.6) make it poorly permeable through the stratum corneum, necessitating specialized formulations containing chemical permeation enhancers (CPEs), such as propylene glycol and Transcutol®, to facilitate dermal and subdermal delivery6,7.  \nBeyond its established antidiabetic role, Met exhibits potent anti-inflammatory, anti-fibrotic, and tissueregenerative effects mediated by AMP-activated protein kinase (AMPK) activation and high mobility group box1 (HMGB1) inhibition—mechanisms directly relevant to musculoskeletal and cutaneous disorders8–11. A prior study from our research group has shown that Met treat","cbCainUVOSlxhGnN","https://ap.wps.com/l/cbCainUVOSlxhGnN","pdf",3813576,13,"English","# Introduction\n## Skin barrier and transdermal delivery\n## Rationale for metformin topical/transdermal use\n## Study aim and comparison design\n# Results\n## Permeation testing and analytical methods","[{\"question\":\"Why is metformin difficult to deliver through the skin?\",\"answer\":\"Metformin is highly hydrophilic and extremely polar, which restricts passive diffusion through the stratum corneum and limits transdermal delivery without specialized formulations.\"},{\"question\":\"Which lotion formulation produced the greatest permeation in human skin?\",\"answer\":\"The formulation containing PG and Transcutol® (PG + T) markedly increased cumulative permeation and flux, while glycerol (Gly) and PG alone showed minimal permeation.\"},{\"question\":\"How did porcine skin permeability compare with human skin in this study?\",\"answer\":\"Porcine skin showed consistently higher permeability across all formulations (Gly \\u003c PG \\u003c PG+T), suggesting it may overestimate human permeability for hydrophilic drugs.\"}]","Comparative human and porcine skin permeation profiles of novel metformin lotion formulations | PDF",1790732731,33]