Pharmacokinetics and tissue distribution of isoniazid released from albumin nanoparticles loaded with isoniazid and rifampicin in rabbit spine

English Keywords:Nanoparticle  Isoniazid  Spine  Paravertebral muscle  RP-HPLC  Pharmacokinetics

English Abstract:

  【Abstract】 Objectives: To study the pharmacokinetics and tissue distribution of isoniazid(INH) released from albumin nanoparticles loaded with isoniazid and rifampicin(INH-RFP-BSA-NPs) in rabbit′s spine and paravertebral muscles after intravenous administration. Methods: 132 healthy New Zealand white rabbits were averagely divided into 2 groups at random. The regular dosage formed INH preparations as control. Then tissue samples were obtained at certain time points(1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 120h). The pharmacokinetics were tested after injection of INH-RFP-BSA-NPs and INH solution via the rabbit′s ear vein. Drug concentration of INH in vertebral and paravertebral muscle tissues was detected by reversed-phase high-performance liquid chromatography(RP-HPLC) method at each time point. The main parameters of pharmacokinetics, including area under concentration-time curve(AUC), half life period(t1/2) and the mean residence time(MRT) were calculated by DAS 3.2.1. Drug targeting index(DTI) and relative targeting efficiency (RTE) were applied to assess the targeting ability of INH-RFP-BSA-NPs. Results: At each time point, INH concentration in the experimental group was slightly higher than that in control group. Pharmacokinetic results of experimental group were AUC0→∞ as (533.71±162.44)μg/g·h, t1/2 as (55.32±38.38)h, MRT as (58.12±44.26)h in rabbit′s spine; AUC0→∞ as (17.40±4.89)μg/g·h, t1/2 as (25.78±6.05)h, MRT as (27.77±8.51)h in rabbit′s paravertebral muscles. Those of control group were AUC0→∞ as (278.61±41.90)μg/g·h, t1/2 as (14.90±7.10)h, MRT as (18.92±6.11)h in rabbit′s spine. In rabbit′s paravertebral muscles, AUC0→∞ was (7.380.93)μg/g·h, t1/2 was (5.97±2.68)h, MRT was (5.20±0.8)h. Compared with INH solution, its AUC was significantly higher(P＜0.01) after intravenous injection of INH-RFP-BSA-NPs, MRT and t1/2 were prolonged(P＜0.05 or P＜0.01). RTE and DTI were greater than one. Conclusions: Comparing to the general formulation of INH, INH-RFP-BSA-NPs can effectively improve the pharmacokinetics behaviour and have more prolonged release effect in rabbit′s spine.