Water is a major limiting factor for food production and many countries fail to produce sufficient food for their population due to severe water scarcity （Jury and Vaux, 2005）. Rice is the main staple food worldwide...Water is a major limiting factor for food production and many countries fail to produce sufficient food for their population due to severe water scarcity （Jury and Vaux, 2005）. Rice is the main staple food worldwide. More than 50% of rice in the world is rain-fed and drought causes severe reduction in rice grain yield in rain-fed environments （Venuprasad et al., 2007; Zhang, 2007; Sandhu et al., 2014）. Therefore, enhancing drought resistance （DR） of rice is important for food security. However, DR is a complex trait, which is controlled by a large number of loci with small effect and is also affected by different genetic background, genotype-by-environment interaction and other stresses such as heat （Hu and Xiong, 2014）.展开更多
胰高血糖素样肽-1受体激动剂(glucagon like peptide-1 receptor agonists,GLP-1RAs)药物是近年来的研究热门,在降低血糖和治疗心血管疾病等领域有突出的效果,司美格鲁肽是其中的代表药物。本文以科普文的形式简要介绍司美格鲁肽的降糖...胰高血糖素样肽-1受体激动剂(glucagon like peptide-1 receptor agonists,GLP-1RAs)药物是近年来的研究热门,在降低血糖和治疗心血管疾病等领域有突出的效果,司美格鲁肽是其中的代表药物。本文以科普文的形式简要介绍司美格鲁肽的降糖机理、功能结构、副作用,以及渗透促进剂8-(2-羟基苯甲酰胺基)辛酸钠(salcaprozate sodium,SNAC)在司美格鲁肽口服制剂中的关键作用,致力于让读者在感受药物分子设计魅力的同时,进一步强化合理用药观念。展开更多
Permeation enhancers(PEs),such as N-[8-(2-hydroxybenzoyl)amino]-caprylate(SNAC),have been reported to improve the oral absorption of various macromolecules.However,the bioavailabilities of these formulations are quite...Permeation enhancers(PEs),such as N-[8-(2-hydroxybenzoyl)amino]-caprylate(SNAC),have been reported to improve the oral absorption of various macromolecules.However,the bioavailabilities of these formulations are quite low and variable due to the influences of enzymes,pH and other gastrointestinal barriers.In this study,we revealed that SNAC could interact with insulin to form tight complexes in a specific concentration(insulin≥ 40μg/mL)-,ratio(SNAC/insulin≥ 20:1)-and pH(≥ 6.8)-dependent manner,thus contributing to a significantly high efficacy of oral insulin delivery.Specifically,absorption mechanism studies revealed that the SNAC/insulin complexes were internalized into the cells by passive diffusion and remained intact when transported in the cytosol.Furthermore,the complexes accelerated the exocytosis of insulin to the basolateral side,thereby enhancing its intestinal mucosal permeability.Eudragit;S100-entrapped SNAC/insulin microspheres were then prepared and exhibited an apparent permeability coefficient(P;) that was 6,6-fold higher than that of the insulin solution.In diabetic rats,hypoglycemic activity was sustained for more than 10 h after the microspheres were loaded into entericcoated capsules.Further pharmacokinetic studies revealed an approximately 6.3% oral bioavailability in both the fasted and fed states,indicating a negligible food effect.Collectively,this study provides insight into the interaction between PEs and payloads and presents an SNAC-based oral insulin delivery system that has high oral bioavailability and patient-friendly medication guidance.展开更多
基金supported by grants from the National Program for Basic Research of China(No.2012CB114305)the National Program on High Technology Development(No. 2012AA10A303)the Oversea Graduate Program from Ministry of Education to K.Songyikhangsuthor
文摘Water is a major limiting factor for food production and many countries fail to produce sufficient food for their population due to severe water scarcity （Jury and Vaux, 2005）. Rice is the main staple food worldwide. More than 50% of rice in the world is rain-fed and drought causes severe reduction in rice grain yield in rain-fed environments （Venuprasad et al., 2007; Zhang, 2007; Sandhu et al., 2014）. Therefore, enhancing drought resistance （DR） of rice is important for food security. However, DR is a complex trait, which is controlled by a large number of loci with small effect and is also affected by different genetic background, genotype-by-environment interaction and other stresses such as heat （Hu and Xiong, 2014）.
基金financial support from the National Natural Science Foundation of China (Nos. 81773651,82025032 and 82073773)NN-CAS foundation+3 种基金National Key R&D Program of China (No. 2020YFE0201700)Chinese Pharmacopoeia Commission (Nos. 2021Y30 and 2021Y25)the Shanghai Science and Technology Committee (No. 18430721600)the Major International Joint Research Project of Chinese Academy of Sciences(No. 153631KYSB20190020。
文摘Permeation enhancers(PEs),such as N-[8-(2-hydroxybenzoyl)amino]-caprylate(SNAC),have been reported to improve the oral absorption of various macromolecules.However,the bioavailabilities of these formulations are quite low and variable due to the influences of enzymes,pH and other gastrointestinal barriers.In this study,we revealed that SNAC could interact with insulin to form tight complexes in a specific concentration(insulin≥ 40μg/mL)-,ratio(SNAC/insulin≥ 20:1)-and pH(≥ 6.8)-dependent manner,thus contributing to a significantly high efficacy of oral insulin delivery.Specifically,absorption mechanism studies revealed that the SNAC/insulin complexes were internalized into the cells by passive diffusion and remained intact when transported in the cytosol.Furthermore,the complexes accelerated the exocytosis of insulin to the basolateral side,thereby enhancing its intestinal mucosal permeability.Eudragit;S100-entrapped SNAC/insulin microspheres were then prepared and exhibited an apparent permeability coefficient(P;) that was 6,6-fold higher than that of the insulin solution.In diabetic rats,hypoglycemic activity was sustained for more than 10 h after the microspheres were loaded into entericcoated capsules.Further pharmacokinetic studies revealed an approximately 6.3% oral bioavailability in both the fasted and fed states,indicating a negligible food effect.Collectively,this study provides insight into the interaction between PEs and payloads and presents an SNAC-based oral insulin delivery system that has high oral bioavailability and patient-friendly medication guidance.
