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

Figures & data

Table 1. The P_app of puerarin and the TEER of the BBB model at 120 min associated with the action of borneol (n = 3).

Concentration of borneol (μg/mL)	0 (the control group)	6.25	12.5	25	50	100
Papp (×10^−6 cm·s)	1.9 ± 0.5	1.7 ± 0.8	13.2 ± 0.2^a	13.1 ± 0.1^a	13.8 ± 1.9^a	11.1 ± 1.8^a
TEER (Ω·cm^2)	221.0 ± 21.1	204.0 ± 21.5	99.1 ± 9.1^a	102.4 ± 7.2^a	93.6 ± 7.5^a	95.7 ± 7.2^a

^ap < 0.01 compared with the control group not containing borneol.

Figure 1. Mean concentration-time curves of puerarin in (A) plasma and (B) brain after administration of puerarin (200 mg/kg) NCS without or with different dose of borneol (25, 50, 100 mg/kg) in mice (n = 6).

Table 2. Pharmacokinetic parameters of puerarin in mice plasma after administration of puerarin (200 mg/kg) NCS without or with different dose of borneol (25, 50, 100 mg/kg) (n = 6).

Parameters	Puerarin NCS without borneol	Puerarin NCS with borneol of 25 mg/kg	Puerarin NCS with borneol of 50 mg/kg	Puerarin NCS with borneol of 100 mg/kg
AUC(0 − 12 h) (ng/mL*h)	3511.42 ± 583.86	3877.15 ± 367.46	6788.15 ± 1288.18^b^,^d	7594.67 ± 649.29^b^,^d
t1/2 (h)	1.90 ± 0.32	2.55 ± 0.65	2.76 ± 0.27^b	1.93 ± 0.41^e
Tmax (h)	1.00 ± 0.00	0.69 ± 0.24^a	0.60 ± 0.14^b	1.00 ± 0.00^d^,^f
Cmax (ng/mL)	1076.02 ± 160.52	1264.67 ± 121.95	1645.25 ± 193.03^b^,^c	2108.22 ± 140.54^b^,^e

^ap < 0.05 compared with the control group without borneol.

^b p < 0.01 compared with the control group without borneol.

^c p < 0.05 compared with the group of 25 mg/kg of borneol.

^d p < 0.01 compared with the group of 25 mg/kg of borneol.

^e p < 0.05 compared with the group of 50 mg/kg of borneol.

^f p < 0.01 compared with the group of 50 mg/kg of borneol.

Table 3. Pharmacokinetic parameters of puerarin in mice brain after administration of puerarin (200 mg/kg) NCS without or with different dose of borneol (25, 50, 100 mg/kg) (n = 6).

Parameters	Puerarin NCS without borneol	Puerarin NCS with borneol of 25 mg/kg	Puerarin NCS with borneol of 50 mg/kg	Puerarin NCS with borneol of 100 mg/kg
AUC0–12 h (ng/mL × h)	214.13 ± 22.05	391.76 ± 80.91^a	941.46 ± 310.30^a^,^c	1303.75 ± 387.47^b^,^c
t1/2 (h)	2.57 ± 0.69	2.72 ± 0.52	4.03 ± 0.76	4.30 ± 1.63
Tmax (h)	1 ± 0	0.83 ± 0.29	1.00 ± 0	1.13 ± 0.60
Cmax (ng/mL)	112.66 ± 9.94	143.93 ± 12.58	213.34 ± 47.57^a	220.25 ± 69.29^a

^ap < 0.05 compared with the control group without borneol.

^b p < 0.01 compared with the control group without borneol.

^c p < 0.05 compared with the group of 25 mg/kg of borneol.

Figure 2. Mean concentration-time curves of puerarin in (A) plasma and (B) brain after administration of NCS, ICS and SMEDDS containing both puerarin (200 mg/kg) and borneol (100 mg/kg) in mice (n = 6).

Table 4. Pharmacokinetic parameters of puerarin in mice plasma after administration of NCS, ICS and SMEDDS containing both puerarin (200 mg/kg) and borneol (100 mg/kg) (n = 6).

Parameters	NCS	SMEDDS	ICS
AUC(0–12 h) (ng/mL × h)	7594.67 ± 649.29	13 174.16 ± 2487.95^b	5783.78 ± 1253.09^c
t1/2 (h)	1.93 ± 0.41	4.34 ± 1.28^a	4.69 ± 0.45^b
Tmax (h)	1.00 ± 0.00	0.83 ± 0.20	0.96 ± 0.10
Cmax (ng/mL)	2108.22 ± 140.54	2844.30 ± 395.32^a	1217.02 ± 288.03^b^,^c

^ap < 0.05 compared with NCS.

^b p < 0.01 compared with NCS.

^c p < 0.01 compared with SMEDDS.

Table 5. Pharmacokinetic parameters of puerarin in mice brain after administration of NCS, ICS and SMEDDS containing both of puerarin (200 mg/kg) and borneol (100 mg/kg) (n = 6).

Parameters	NCS	SMEDDS	ICS
AUC(0–12 h) (ng/mL × h)	1303.75 ± 387.47	2199.81 ± 328.98^b	1488.09 ± 299.92^c
t1/2 (h)	4.30 ± 1.63	5.71 ± 1.03	2.20 ± 0.49^a^,^d
Tmax (h)	1.13 ± 0.60	0.85 ± 0.22	0.75 ± 0.18
Cmax (ng/mL)	220.25 ± 69.29	462.48 ± 55.75^b	385.94 ± 84.61^a

^ap < 0.05 compared with NCS.

^b p < 0.01 compared with NCS.

^c p < 0.05 compared with SMEDDS.

^d p < 0.01 compared with SMEDDS.