The authors regret that an error in Fig.3E in this article was found while we reviewing the published data.An inadvertent mistake occurred in the process of assembling images.The picture of the Ms215μg/mL group was w...The authors regret that an error in Fig.3E in this article was found while we reviewing the published data.An inadvertent mistake occurred in the process of assembling images.The picture of the Ms215μg/mL group was wrongly placed.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
文摘The authors regret that an error in Fig.3E in this article was found while we reviewing the published data.An inadvertent mistake occurred in the process of assembling images.The picture of the Ms215μg/mL group was wrongly placed.
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.
