Exosomes,as promising vehicles,have been widely used in the research of oral drug delivery,but the generally low drug loading efficiency of exosomes seriously limits its application and transformation.In this study,we...Exosomes,as promising vehicles,have been widely used in the research of oral drug delivery,but the generally low drug loading efficiency of exosomes seriously limits its application and transformation.In this study,we systematically investigated the effects of drug loading methods and physicochemical properties(lipophilicity and molecular weight)on drug loading efficiency of milk-derived exosomes to explore the most appropriate loading conditions.Our finding revealed that the drug loading efficiency of exosomes was closely related to the drug loading method,drug lipophilicity,drug molecular weight and exosome/drug proportions.Of note,we demonstrated the universality that hydrophilic biomacromolecule drugs were the most appropriate loading drugs for milk-derived exosomes,which was attributed to the efficient loading capacity and sustained release behavior.Furthermore,milk-derived exosomes could significantly improve the transepithelial transport and oral bioavailability of model hydrophilic biomacromolecule drugs(octreotide,exendin-4 and salmon calcitonin).Collectively,our results suggested that the encapsulation of hydrophilic biomacromolecule drugs might be the most promising direction for milk exosomes as oral drug delivery vehicles.展开更多
The gastrointestinal tract of livestock and poultry is prone to challenge by feedborne antigens,pathogens,and other stress factors in the farm environment.Excessive physiological inflammation and oxidative stress that...The gastrointestinal tract of livestock and poultry is prone to challenge by feedborne antigens,pathogens,and other stress factors in the farm environment.Excessive physiological inflammation and oxidative stress that arises firstly disrupts the intestinal epithelial barrier followed by other components of the gastrointestinal tract.In the present review,the interrelationship between intestinal barrier inflammation and oxidative stress that contributes to the pathogenesis of inflammatory bowel disease was described.Further,the role of naturally existing immunomodulatory nutrients such as the omega-3 polyunsaturated fatty acids,citrus pectin,and milk-derived exosomes in preventing intestinal barrier inflammation was discussed.Based on the existing evidence,the possible molecular mechanism of these bioactive nutrients in the intestinal barrier was outlined for application in animal diets.展开更多
As endogenous courier vesicles,exosomes play crucial roles in macromolecule transmission and intercellular communication.Therefore,exosomes have drawn increasing attention as biomimetic drug-delivery vehicles over the...As endogenous courier vesicles,exosomes play crucial roles in macromolecule transmission and intercellular communication.Therefore,exosomes have drawn increasing attention as biomimetic drug-delivery vehicles over the past few years.However,few studies have investigated the encapsulation of peptide/protein drugs into exosomes for oral administration.Additionally,the mechanisms underlying their biomimetic properties as oral delivery vehicles remain unknown.Herein,insulin-loaded milk-derived exosomes(EXO@INS)were fabricated and the in vivo hypoglycemic effect was investigated on type I diabetic rats.Surprisingly,EXO@INS(50 and 30 IU/kg)elicited a more superior and more sustained hypoglycemic effect compared with that obtained with subcutaneously injected insulin.Further mechanism studies indicated that the origin of excellent oral-performance of milk-derived exosomes combined active multi-targeting uptake,pH adaptation during gastrointestinal transit,nutrient assimilation related ERK1/2 and p38 MAPK signal pathway activation and intestinal mucus penetration.This study provides the first demonstration that multifunctional milk-derived exosomes offer solutions to many of the challenges arising from oral drug delivery and thus provide new insights into developing naturally-equipped nanovehicles for oral drug administration.展开更多
The aim of the study was to examine microorganisms in samples of fer<span style="font-family:;" "="">mented milk beverage and water from dairy under state inspection. In a dairy located ...The aim of the study was to examine microorganisms in samples of fer<span style="font-family:;" "="">mented milk beverage and water from dairy under state inspection. In a dairy located in the Rec<span style="color:#4F4F4F;font-family:-apple-system, "font-size:16px;white-space:normal;background-color:#FFFFFF;">ô</span>ncavo of Bahia, fifteen samples of fermented milk beverage were <span>collected, corresponding to three different batches, and six water samples</span>, two from each point of use in the industry: Point 1</span><span style="font-family:;" "="">—<span>Sanitary barrier;Point <span>2</span></span><span>—<span>Internal faucet for cleaning surfaces and utensils;Point 3</span>—<span>Drinking</span></span><span> fountain for employees. All samples were submitted to microbiological research of total coliforms, <i>Escherichia coli</i> and <i>Aeromonas</i> spp. In the water samples, there was also quantification of heterotrophic bacteria and analysis of free residual chlorine. The fermented milk beverage samples did not show growth of total coliforms, <i>E. coli</i> and <i>Aeromonas</i> spp. With regard to water, no sample showed measurable levels of free residual chlorine, while in the microbiolog<span>ical analysis the count of heterotrophic bacteria in the drinking water exceeded the limit established by legislation (5.6 </span></span><span>×<span> 10<sup>2</sup> CFU<span style="color:#4F4F4F;font-family:-apple-system, "font-size:16px;white-space:normal;background-color:#F7F7F7;">.</span>mL<sup>-1</sup>). In addition, the water from the sanitary barrier revealed total coliforms above the allowed</span></span><span> <span>value (1.3 </span></span><span>× <span>10<sup>1</sup> CFU<span style="color:#4F4F4F;font-family:-apple-system, "font-size:16px;white-space:normal;background-color:#F7F7F7;">.</span>100 mL<sup>-1</sup>) and showed contamination by <i>Aeromonas</i></span></span><span> spp. (7.0 </span>×<span> 10<sup>1</sup> CFU<span style="color:#4F4F4F;font-family:-apple-system, "font-siz展开更多
基金The authors gratefully acknowledge financial support from National Natural Science Foundation of China(81872818)National Key R&D Program of China(2021YFE0115200).
文摘Exosomes,as promising vehicles,have been widely used in the research of oral drug delivery,but the generally low drug loading efficiency of exosomes seriously limits its application and transformation.In this study,we systematically investigated the effects of drug loading methods and physicochemical properties(lipophilicity and molecular weight)on drug loading efficiency of milk-derived exosomes to explore the most appropriate loading conditions.Our finding revealed that the drug loading efficiency of exosomes was closely related to the drug loading method,drug lipophilicity,drug molecular weight and exosome/drug proportions.Of note,we demonstrated the universality that hydrophilic biomacromolecule drugs were the most appropriate loading drugs for milk-derived exosomes,which was attributed to the efficient loading capacity and sustained release behavior.Furthermore,milk-derived exosomes could significantly improve the transepithelial transport and oral bioavailability of model hydrophilic biomacromolecule drugs(octreotide,exendin-4 and salmon calcitonin).Collectively,our results suggested that the encapsulation of hydrophilic biomacromolecule drugs might be the most promising direction for milk exosomes as oral drug delivery vehicles.
基金a European Joint Doctorate Degree programme in Molecular Animal Nutrition(MANNA)between University of Milan(Italy)and University of Veterinary Medicine and Pharmacy in Kosice(Slovakia)funding from the European Union’s Horizon 2020 programme under the Marie Slodowska-Curie Grant agreement No 765423.
文摘The gastrointestinal tract of livestock and poultry is prone to challenge by feedborne antigens,pathogens,and other stress factors in the farm environment.Excessive physiological inflammation and oxidative stress that arises firstly disrupts the intestinal epithelial barrier followed by other components of the gastrointestinal tract.In the present review,the interrelationship between intestinal barrier inflammation and oxidative stress that contributes to the pathogenesis of inflammatory bowel disease was described.Further,the role of naturally existing immunomodulatory nutrients such as the omega-3 polyunsaturated fatty acids,citrus pectin,and milk-derived exosomes in preventing intestinal barrier inflammation was discussed.Based on the existing evidence,the possible molecular mechanism of these bioactive nutrients in the intestinal barrier was outlined for application in animal diets.
基金We gratefully acknowledge financial support from the National Science Foundation for Distinguished Young Scholars(81625023,China)the National Natural Science Foundation of China(81872818)the Major Research Plan of National Natural Science Foundation of China(81690261).
文摘As endogenous courier vesicles,exosomes play crucial roles in macromolecule transmission and intercellular communication.Therefore,exosomes have drawn increasing attention as biomimetic drug-delivery vehicles over the past few years.However,few studies have investigated the encapsulation of peptide/protein drugs into exosomes for oral administration.Additionally,the mechanisms underlying their biomimetic properties as oral delivery vehicles remain unknown.Herein,insulin-loaded milk-derived exosomes(EXO@INS)were fabricated and the in vivo hypoglycemic effect was investigated on type I diabetic rats.Surprisingly,EXO@INS(50 and 30 IU/kg)elicited a more superior and more sustained hypoglycemic effect compared with that obtained with subcutaneously injected insulin.Further mechanism studies indicated that the origin of excellent oral-performance of milk-derived exosomes combined active multi-targeting uptake,pH adaptation during gastrointestinal transit,nutrient assimilation related ERK1/2 and p38 MAPK signal pathway activation and intestinal mucus penetration.This study provides the first demonstration that multifunctional milk-derived exosomes offer solutions to many of the challenges arising from oral drug delivery and thus provide new insights into developing naturally-equipped nanovehicles for oral drug administration.
文摘The aim of the study was to examine microorganisms in samples of fer<span style="font-family:;" "="">mented milk beverage and water from dairy under state inspection. In a dairy located in the Rec<span style="color:#4F4F4F;font-family:-apple-system, "font-size:16px;white-space:normal;background-color:#FFFFFF;">ô</span>ncavo of Bahia, fifteen samples of fermented milk beverage were <span>collected, corresponding to three different batches, and six water samples</span>, two from each point of use in the industry: Point 1</span><span style="font-family:;" "="">—<span>Sanitary barrier;Point <span>2</span></span><span>—<span>Internal faucet for cleaning surfaces and utensils;Point 3</span>—<span>Drinking</span></span><span> fountain for employees. All samples were submitted to microbiological research of total coliforms, <i>Escherichia coli</i> and <i>Aeromonas</i> spp. In the water samples, there was also quantification of heterotrophic bacteria and analysis of free residual chlorine. The fermented milk beverage samples did not show growth of total coliforms, <i>E. coli</i> and <i>Aeromonas</i> spp. With regard to water, no sample showed measurable levels of free residual chlorine, while in the microbiolog<span>ical analysis the count of heterotrophic bacteria in the drinking water exceeded the limit established by legislation (5.6 </span></span><span>×<span> 10<sup>2</sup> CFU<span style="color:#4F4F4F;font-family:-apple-system, "font-size:16px;white-space:normal;background-color:#F7F7F7;">.</span>mL<sup>-1</sup>). In addition, the water from the sanitary barrier revealed total coliforms above the allowed</span></span><span> <span>value (1.3 </span></span><span>× <span>10<sup>1</sup> CFU<span style="color:#4F4F4F;font-family:-apple-system, "font-size:16px;white-space:normal;background-color:#F7F7F7;">.</span>100 mL<sup>-1</sup>) and showed contamination by <i>Aeromonas</i></span></span><span> spp. (7.0 </span>×<span> 10<sup>1</sup> CFU<span style="color:#4F4F4F;font-family:-apple-system, "font-siz
