Alexis Bages , Mickaël Castelain , Nicolas Dietrich , Rosanne Raynal , Karim Ioualalen
{"title":"疏水性固体脂质微粒,用于保护胃敏感的亲水性活性生物分子,口服治疗 EPI。","authors":"Alexis Bages , Mickaël Castelain , Nicolas Dietrich , Rosanne Raynal , Karim Ioualalen","doi":"10.1016/j.ejpb.2024.114504","DOIUrl":null,"url":null,"abstract":"<div><div>Exocrine Pancreatic Insufficiency (EPI), induced by conditions such as cystic fibrosis, chronic pancreatitis, and Crohn’s disease, is a frequently overlooked and underdiagnosed gastrointestinal disorder. It leads to inadequate intestinal digestion due to insufficient secretion of pancreatic juice, resulting in discomfort, pain, and ultimately severe malnutrition. Despite numerous treatments proving ineffective over the past three decades, a strictly hydrophobic solid lipid formulation, administered orally, is proposed in this study to restore digestive function. This technology relies on the hydrophobic nature of the matrix to physically protect the hydrophilic active principle from the gastric environment while enabling its immediate release in the duodenum by targeting the amphiphilic nature of bile salts. Results demonstrate that this formulation effectively protects an acid-sensitive active ingredient during gastric passage (Simulated Gastric Fluid or SGF), facilitating its rapid release upon entering an artificial duodenal environment (Simulated Intestinal Fluid or SIF). Furthermore, it has been demonstrated that the preservation of a protein-based active ingredient extends beyond its primary protein structure to include its functional aspects, such as enzymatic activity. This drug delivery technology could enable the protection of hydrophilic active biomolecules, such as pancreatin, which are sensitive to gastric acidity, while promoting their immediate release upon contact with bile salts in the proximal duodenum, with the ultimate goal of correcting the digestive defect induced by EPI.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"204 ","pages":"Article 114504"},"PeriodicalIF":4.4000,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Hydrophobic solid lipid-based microparticles for the protection of gastric-sensitive hydrophilic active biomolecules for oral administration in the treatment of EPI\",\"authors\":\"Alexis Bages , Mickaël Castelain , Nicolas Dietrich , Rosanne Raynal , Karim Ioualalen\",\"doi\":\"10.1016/j.ejpb.2024.114504\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Exocrine Pancreatic Insufficiency (EPI), induced by conditions such as cystic fibrosis, chronic pancreatitis, and Crohn’s disease, is a frequently overlooked and underdiagnosed gastrointestinal disorder. It leads to inadequate intestinal digestion due to insufficient secretion of pancreatic juice, resulting in discomfort, pain, and ultimately severe malnutrition. Despite numerous treatments proving ineffective over the past three decades, a strictly hydrophobic solid lipid formulation, administered orally, is proposed in this study to restore digestive function. This technology relies on the hydrophobic nature of the matrix to physically protect the hydrophilic active principle from the gastric environment while enabling its immediate release in the duodenum by targeting the amphiphilic nature of bile salts. Results demonstrate that this formulation effectively protects an acid-sensitive active ingredient during gastric passage (Simulated Gastric Fluid or SGF), facilitating its rapid release upon entering an artificial duodenal environment (Simulated Intestinal Fluid or SIF). Furthermore, it has been demonstrated that the preservation of a protein-based active ingredient extends beyond its primary protein structure to include its functional aspects, such as enzymatic activity. This drug delivery technology could enable the protection of hydrophilic active biomolecules, such as pancreatin, which are sensitive to gastric acidity, while promoting their immediate release upon contact with bile salts in the proximal duodenum, with the ultimate goal of correcting the digestive defect induced by EPI.</div></div>\",\"PeriodicalId\":12024,\"journal\":{\"name\":\"European Journal of Pharmaceutics and Biopharmaceutics\",\"volume\":\"204 \",\"pages\":\"Article 114504\"},\"PeriodicalIF\":4.4000,\"publicationDate\":\"2024-09-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Pharmaceutics and Biopharmaceutics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0939641124003308\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Pharmaceutics and Biopharmaceutics","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0939641124003308","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Hydrophobic solid lipid-based microparticles for the protection of gastric-sensitive hydrophilic active biomolecules for oral administration in the treatment of EPI
Exocrine Pancreatic Insufficiency (EPI), induced by conditions such as cystic fibrosis, chronic pancreatitis, and Crohn’s disease, is a frequently overlooked and underdiagnosed gastrointestinal disorder. It leads to inadequate intestinal digestion due to insufficient secretion of pancreatic juice, resulting in discomfort, pain, and ultimately severe malnutrition. Despite numerous treatments proving ineffective over the past three decades, a strictly hydrophobic solid lipid formulation, administered orally, is proposed in this study to restore digestive function. This technology relies on the hydrophobic nature of the matrix to physically protect the hydrophilic active principle from the gastric environment while enabling its immediate release in the duodenum by targeting the amphiphilic nature of bile salts. Results demonstrate that this formulation effectively protects an acid-sensitive active ingredient during gastric passage (Simulated Gastric Fluid or SGF), facilitating its rapid release upon entering an artificial duodenal environment (Simulated Intestinal Fluid or SIF). Furthermore, it has been demonstrated that the preservation of a protein-based active ingredient extends beyond its primary protein structure to include its functional aspects, such as enzymatic activity. This drug delivery technology could enable the protection of hydrophilic active biomolecules, such as pancreatin, which are sensitive to gastric acidity, while promoting their immediate release upon contact with bile salts in the proximal duodenum, with the ultimate goal of correcting the digestive defect induced by EPI.
期刊介绍:
The European Journal of Pharmaceutics and Biopharmaceutics provides a medium for the publication of novel, innovative and hypothesis-driven research from the areas of Pharmaceutics and Biopharmaceutics.
Topics covered include for example:
Design and development of drug delivery systems for pharmaceuticals and biopharmaceuticals (small molecules, proteins, nucleic acids)
Aspects of manufacturing process design
Biomedical aspects of drug product design
Strategies and formulations for controlled drug transport across biological barriers
Physicochemical aspects of drug product development
Novel excipients for drug product design
Drug delivery and controlled release systems for systemic and local applications
Nanomaterials for therapeutic and diagnostic purposes
Advanced therapy medicinal products
Medical devices supporting a distinct pharmacological effect.