Permeability of breviscapine liposomes from blood circulation to brain intracellular space in rats studied using microdialysis

摘要

To investigate permeability of breviscapine liposomes from blood circulation to brain intracellular space in rats. Methods: Breviscapine is the flavonoid constituents extracted from Chinese herb. Scutellarin is the primary active ingredient of breviscapine. It is a sort of flavone glycoside. In China, the preparations of breviscapine are extensively used as for the treatment of cerebrovascular diseases. In order to prolong the residence of breviscapine in blood and deliver more breviscapine into brain, breviscapine liposomes were prepared and permeability of breviscapine liposomes from blood circulation to brain intracellular space was investigated in rats. The permeation of drug from blood circulation to brain intracellular space (ICS) consists of two steps: the BBB permeation and then the brain cell membrane (BCM) permeation. The brain extracellular fluid (ECF) is the first compartment through which a compound must pass after penetrating the BBB. Microdialysis sampling is a method that provides access to the brain ECF. It employs a short length of hollow dialysis fiber, which is permeable to water and small solutes, but excludes large molecules such as proteins and enzymes due to the molecular weight cut-off of the fiber. The correlations between breviscapine concentrations in brain ECF and blood were studied by microdialysis sampling in the rat striatum after intravenous administration of breviscapine liposomes or unencapsulated breviscapine to provide a direct measurement of the BBB permeability. The concentrations in brain ICS were studied by determining the breviscapine concentrations in brain homogemate after intravenous administration. The permeability coefficients at BBB (PBBB) and brain cell membrane (PBCM) were defined as the corresponding ratios of area under concentration time curve (AUC): AUCECF/blood and AUC. Based on the permeability coefficients of unencapsulated brevisacpine in rats, we further studied the permeability of breviscapine liposomes. Results The AUCECF ratios of breviscapine liposome to unencapsulated breviscapine were (275%±39%). The PBBB of breviscapine liposomes and unencapsulated breviscapine were (0.1816±0.0464) and (0.2015±0.0186) respectively and there was no significant difference between breviscapine liposomes and unencapsulated brevisacpine. The PBCM of breviscapine liposomes and unencapsulated brevisacpine were (0.5456±0.0187) and (0.2839±0.0456) respectively and there was significant difference between breviscapine liposomes and unencapsulated brevisacpine. Conclusion: Compared with unencapsulated brevisacpine, brevisacpine liposomes possessd the equal BBB permeability and higher brain cell membrane permeability, which indicated breviscapine liposomes could permeate the BBB and delivered more drug from the blood circulation to the brain intracellular space.