Uptake and Transport Mechanisms of Ginkgolide B Niosomal Composite Drug Through the Blood-Brain Barrier

Cerebrovascular and functional neurological lesions are the major disorders threatening human health and quality of life. The presence of the blood-brain barrier seriously affects the distribution and efficacy of various drugs in the brain. Ginkgolide B (GB) and Puerarin (Pue) are active pharmaceutical ingredients for the treatment of Parkinson's disease. Here, we have developed a novel strategy to construct a GB-Pue niosomal composite drug. The in vitro cytology study of the niosomal composite drug showed that 20 mmol/L glutamate resulted in a mortality of 50-60% in the SHSY-5Y cells, while 30 mu mol/L niosomal composite drug resulted in a survival rate of 95.2% in the SHSY-5Y cells with a maximum uptake value of 3.5 mu g/mg and a peak uptake time at 2 hr. The monolayer cells reached a maximum transepithelial/endothelial electrical resistance (TEER) value of 626 Omega * cm(2) at 36 hr in culture, and the cellular integrity was negatively correlated with the amount of drug accumulated in the cells. The accumulated GB and Pue in cells reached 86.53% and 76.49%, respectively. The 30 mu mol/L composite drug preparation provided a higher cell survival rate in the glutamate (Glu) injured cells compared to the single drug preparations. Therefore, the composite preparation of the two drugs generated a synergistic effect, meeting the requirement for a combined use. The cell transmembrane transport experiments demonstrated that the pharmaceutical preparations traversed the blood- brain barrier through the active transport of cells.