The objective of this paper is to prepare vinpocetine(VIN)inclusion complex and evaluate its brain targeting effect after intranasal administration.In the present study,VIN inclusion complex was prepared in order to i...The objective of this paper is to prepare vinpocetine(VIN)inclusion complex and evaluate its brain targeting effect after intranasal administration.In the present study,VIN inclusion complex was prepared in order to increase its solubility.Stability constant(Kc)was used for host selection.Factors influencing properties of the inclusion complex was investigated.Formation of the inclusion complex was identified by solubility study and DSC analysis.The brain targeting effect of the complex after intranasal administration was studied in rats.It was demonstrated that properties of the inclusion complex was mainly influenced by cyclodextrin type,organic acids type,system pH and host/guest molar ratio.Multiple component complexes can be formed by the addition of citric acid,with solubility improved for more than 23 times.Furthermore,In vivo study revealed that after intranasal administration,the absolute bioavailability of vinpocetine inclusion complex was 88%.Compared with intravenous injection,significant brain targeting effect was achieved after intranasal delivery,with brain targeting index 1.67.In conclusion,by intranasal administration of VIN inclusion complex,a fast onset of action and good brain targeting effect can be achieved.Intranasal route is a promising approach for the treatment of CNS diseases.展开更多
The number of people with Alzheimer’s disease(AD)is increasing annually,with the nidus mainly concentrated in the cortex and hippocampus.Despite of numerous efforts,effective treatment of AD is still facing great cha...The number of people with Alzheimer’s disease(AD)is increasing annually,with the nidus mainly concentrated in the cortex and hippocampus.Despite of numerous efforts,effective treatment of AD is still facing great challenges due to the blood brain barrier(BBB)and limited drug distribution in the AD nidus sites.Thus,in this study,using vinpocetine(VIN)as a model drug,the objective is to explore the feasibility of tackling the above bottleneck via intranasal drug delivery in combination with a brain guider,borneol(BOR),using nanoemulsion(NE)as the carrier.First of all,the NE were prepared and characterized.In vivo behavior of the NE after intranasal administration was investigated.Influence of BOR dose,BOR administration route on drug brain targeting behavior was evaluated,and the influence of BOR addition on drug brain subregion distribution was probed.It was demonstrated that all the NE had comparable size and similar retention behavior after intranasal delivery.Compared to intravenous injection,improved brain targeting effect was observed by intranasal route,and drug targeting index(DTI)of the VIN–NE group was 154.1%,with the nose-to-brain direct transport percentage(DTP)35.1%.Especially,remarkably enhanced brain distribution was achieved after BOR addition in the NE,with the extent depending on BOR dose.VIN brain concentration was the highest in the VIN-1-BOR-NE group at BOR dose of 1 mg/kg,with the DTI reaching 596.1%and the DTP increased to 83.1%.BOR could exert better nose to brain delivery when administrated together with the drug via intranasal route.Notably,BOR can remarkably enhance drug distribution in both hippocampus and cortex,the nidus areas of AD.In conclusion,in combination with intranasal delivery and the intrinsic brain guiding effect of BOR,drug distribution not only in the brain but also in the cortex and hippocampus can be enhanced significantly,providing the perquisite for improved therapeutic efficacy of AD.展开更多
文摘The objective of this paper is to prepare vinpocetine(VIN)inclusion complex and evaluate its brain targeting effect after intranasal administration.In the present study,VIN inclusion complex was prepared in order to increase its solubility.Stability constant(Kc)was used for host selection.Factors influencing properties of the inclusion complex was investigated.Formation of the inclusion complex was identified by solubility study and DSC analysis.The brain targeting effect of the complex after intranasal administration was studied in rats.It was demonstrated that properties of the inclusion complex was mainly influenced by cyclodextrin type,organic acids type,system pH and host/guest molar ratio.Multiple component complexes can be formed by the addition of citric acid,with solubility improved for more than 23 times.Furthermore,In vivo study revealed that after intranasal administration,the absolute bioavailability of vinpocetine inclusion complex was 88%.Compared with intravenous injection,significant brain targeting effect was achieved after intranasal delivery,with brain targeting index 1.67.In conclusion,by intranasal administration of VIN inclusion complex,a fast onset of action and good brain targeting effect can be achieved.Intranasal route is a promising approach for the treatment of CNS diseases.
基金supported by the Distinguished Professor Project of Liaoning Province.
文摘The number of people with Alzheimer’s disease(AD)is increasing annually,with the nidus mainly concentrated in the cortex and hippocampus.Despite of numerous efforts,effective treatment of AD is still facing great challenges due to the blood brain barrier(BBB)and limited drug distribution in the AD nidus sites.Thus,in this study,using vinpocetine(VIN)as a model drug,the objective is to explore the feasibility of tackling the above bottleneck via intranasal drug delivery in combination with a brain guider,borneol(BOR),using nanoemulsion(NE)as the carrier.First of all,the NE were prepared and characterized.In vivo behavior of the NE after intranasal administration was investigated.Influence of BOR dose,BOR administration route on drug brain targeting behavior was evaluated,and the influence of BOR addition on drug brain subregion distribution was probed.It was demonstrated that all the NE had comparable size and similar retention behavior after intranasal delivery.Compared to intravenous injection,improved brain targeting effect was observed by intranasal route,and drug targeting index(DTI)of the VIN–NE group was 154.1%,with the nose-to-brain direct transport percentage(DTP)35.1%.Especially,remarkably enhanced brain distribution was achieved after BOR addition in the NE,with the extent depending on BOR dose.VIN brain concentration was the highest in the VIN-1-BOR-NE group at BOR dose of 1 mg/kg,with the DTI reaching 596.1%and the DTP increased to 83.1%.BOR could exert better nose to brain delivery when administrated together with the drug via intranasal route.Notably,BOR can remarkably enhance drug distribution in both hippocampus and cortex,the nidus areas of AD.In conclusion,in combination with intranasal delivery and the intrinsic brain guiding effect of BOR,drug distribution not only in the brain but also in the cortex and hippocampus can be enhanced significantly,providing the perquisite for improved therapeutic efficacy of AD.
