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

Abstract

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 μmol/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 μg/mg and a peak uptake time at 2 hr. The monolayer cells reached a maximum transepithelial/endothelial electrical resistance (TEER) value of 626 Ω*cm2 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 μmol/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.