Enhancing both oral bioavailability and brain penetration of puerarin using borneol in combination with preparation technologies

Abstract

Now there are few good oral preparations of puerarin used in cerebrovascular diseases because of its poor oral absorption caused by the low water solubility and the poor penetration into brain. In this study, three oral formulations of puerarin, nanocrystals suspension (NCS), inclusion compounds solution (ICS) and self-microemulsifying drug delivery system (SMEDDS) were prepared with borneol as an oral brain-targeting enhancer. A rat syngeneic in vitro model of the brain-blood barrier (BBB) was established to investigate effects of borneol on the permeability of puerarin across the BBB. The pharmacokinetics of puerarin in mice after oral administration was investigated by a high performance liquid chromatography-mass spectrometry/mass spectrometry (HPLC-MS/MS) method. The in vitro BBB model study showed the permeability of puerarin was increased significantly (p < 0.05) and the value of transepithelial electrical resistance at 2 h was decreased significantly (p < 0.01) when the concentration of borneol was over 12.5 μg/mL compared with the control group. The pharmacokinetics results indicated borneol with doses of over 50 mg/kg could obviously increase both intestinal absorption and brain penetration of puerarin. With co-administration of borneol (100 mg/kg), the AUC of puerarin both in plasma (AUC) and in brain (AUC) for SMEDDS were significantly higher than those for NCS (p < 0.01) and ICS (p < 0.05). These results suggested borneol in combination with SMEDDS could improve both the oral absorption and the brain penetration of puerarin in mice, which was promising for the development of an oral formulation of puerarin used in cerebrovascular diseases.

Borneol and Α-asarone as adjuvant agents for improving blood–brain barrier permeability of puerarin and tetramethylpyrazine by activating adenosine receptors

“…These results indicated that oral administration of PUE and TMP combined with borneol or α-asarone had an increased brain distribution. The previous study reported that borneol not only increased brain distribution but also increased oral absorption of PUE, but this study reported only enhanced brain distribution (Yi et al., 2017 ). This may be because the doses of PUE (20 mg/kg) and borneol (25 mg/kg) used in our study were relatively lower than the previous study (PUE: 200 mg/kg, borneol: 50, 100 and 200 mg/kg).…”

“…Then a trans-endothelial electrical resistance (TEER) instrument (EVOM2, WPI, USA) was used to measure the TEER. The TEER value was increasing with cell proliferation, and when the value became consistent (>200 Ω cm 2 ) for seven consecutive days, the in vitro BBB was established (Yi et al., 2017 ; Zhu et al., 2018 ).…”

Current Strategies for Brain Drug Delivery

“…The authors proposed further studies on doses, schedules and combination regimens. Recently, borneol has been studied to increase both oral absorption and brain penetration of drugs in animal models 63 - 65 . Yi et al compared four different oral formulations of puerarin with borneol.…”

“…Yi et al compared four different oral formulations of puerarin with borneol. Among them, a self-microemulsifying drug delivery system containing both puerarin and borneol resulted in significantly higher AUCs both in plasma and in the brain compared to other formulations 65 . It is very likely that co-administration of a drug and a permeability enhancer is insufficient to achieve the benefits of the enhancer in humans, as shown in the previous cereport and regadenoson studies.…”

Gram‐scale separation of borneol and camphor fromCinnamomum camphora(L.) Presl by continuous counter‐current chromatography

“…However, a suitable injection point should be optimized to avoid the peaks of the new sample overlapping the previous sample constituents. In the study, to avoid overlapping peaks, the nth (n > 1) injection point (t jn ) should satisfy equation (4).…”