The first biphasic open one-compartment pharmacokinetic model is described. Its analytical solutions to drug concentration were developed from parameters of an open two-compartment pharmacokinetic model. The model is ...The first biphasic open one-compartment pharmacokinetic model is described. Its analytical solutions to drug concentration were developed from parameters of an open two-compartment pharmacokinetic model. The model is used to explain the unusually large compartment volumes and apparent volumes of distribution of lipophilic drugs, as well as to identify which of the pharmacokinetic parameters of the classical compartment models are biologically relevant.展开更多
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
Aim To investigate the relationship between pH environment of meptazinolhydrochloride (MEP) and its nasal absorption. Methods In situ nasal peifusion was performed to studythe effect of pH environment on the nasal abs...Aim To investigate the relationship between pH environment of meptazinolhydrochloride (MEP) and its nasal absorption. Methods In situ nasal peifusion was performed to studythe effect of pH environment on the nasal absorption. Its effect on the transport from nose tobrain was further researched by in vivo experiment. Results In in situ perfusion experiment, thenasal absorption of MEP in basic environment was significantly higher than that in acid condition,but the difference was not observed in in vivo experiment. Conclusion The pH environment ofmeptazinol hydrocloride in formulation cannot be regarded as an important factor influencing nasalabsorption and transport from nose to brain.展开更多
文摘The first biphasic open one-compartment pharmacokinetic model is described. Its analytical solutions to drug concentration were developed from parameters of an open two-compartment pharmacokinetic model. The model is used to explain the unusually large compartment volumes and apparent volumes of distribution of lipophilic drugs, as well as to identify which of the pharmacokinetic parameters of the classical compartment models are biologically relevant.
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.
文摘Aim To investigate the relationship between pH environment of meptazinolhydrochloride (MEP) and its nasal absorption. Methods In situ nasal peifusion was performed to studythe effect of pH environment on the nasal absorption. Its effect on the transport from nose tobrain was further researched by in vivo experiment. Results In in situ perfusion experiment, thenasal absorption of MEP in basic environment was significantly higher than that in acid condition,but the difference was not observed in in vivo experiment. Conclusion The pH environment ofmeptazinol hydrocloride in formulation cannot be regarded as an important factor influencing nasalabsorption and transport from nose to brain.
