目的 研究阿魏酸在自制线性微透析探针上的体内外回收率与灌流速度、药物浓度之间的关系,并对自制阿魏酸乳剂在大鼠上进行经皮皮肤药动学研究。方法 采用HPLC测定透析液中阿魏酸浓度,考察不同灌流速度、不同药物浓度对探针体外正、反向回收率和体内反向回收率的影响,采用微透析技术进行经皮皮肤药动学研究。结果 自制探针性质稳定;在所研究的浓度和灌流速度的范围内,探针回收率与阿魏酸的药物浓度无关,与灌流速度成反比;探针体外正、反向回收率在灌流流速1.0、2.0 μL·min-1时有显著性差异(P<0.05),探针体外正、反向回收率在3.0 μL·min-1无显著性差异(P>0.05);体内反向回收率低于体外反向回收率,与体外正向回收率无显著性差异(P>0.05)。大鼠经皮药动学表明,阿魏酸乳剂(8.75 mg·cm-2)可在体内维持长时间的药物浓度,AUC0-10 h为(128.30±23.51) mg·h·L-1,ρmax为(19.08±4.39) mg·L-1。结论 在阿魏酸的经皮皮肤药动学研究中,可采用体内反向回收率作为药物的探针回收率来校正;阿魏酸乳剂的经皮吸收能力较好,能长时间释放药物,有望成为新的给药剂型。
Abstract
OBJECTIVE To investigate the relationship between the recovery of ferulic acid on self-made linear microdialysis probes and the perfusion speed and drug concentrations and study, transdermal pharmacokinetics of self-made ferulic acid emulsion in rats. METHODS The ferulic acid in microdialysate was determined by HPLC. The in vitro recovery of ferulic acid was studied using positive dialysis and retrodialysis methods at different flow rates and concentrations. And the in vivo recovery of ferulic acid was studied using retrodialysis methods. The transdermal pharmacokinetics in skin was evaluated using microdialysis. RESULTS The self-made probe was stable. Over the perfusion flow rates and drug concentrations range studied, the probe recovery of ferulic acid was independent of drug concentrations, inversely proportional to the perfusion flow rates. The positive dialysis and retrodialysis recovery of the probe in vitro was significantly different at the perfusion flow rate of 1.0 or 2.0 μL·min-1 (P<0.05), and there was no significant difference at 3.0 μL·min-1 (P>0.05). The retrodialysis probe recovery in vivo was lower than that obtained in vitro, and was no significant difference from the positive dialysis probe recovery in vitro. The transdermal pharmacokinetic results of self-made ferulic acid emulsion showed that it could maintain the drug concentrations for a long time. The AUC0-10 h and ρmax of transdermal administration (8.75 mg·cm-2) was (128.30±23.51) mg·h·L-1 and (19.08±4.39) mg·L-1, respectively. CONCLUSION The retrodialysis probe recovery in vivo method is suitable for ferulic acid skin pharmacokinetic study. The ferulic acid emulsion has good skin absorption and long-time substained release, which can be developed as a novel transdermal preparation.
关键词
阿魏酸 /
微透析 /
探针回收率 /
体内 /
体外 /
经皮药动学
{{custom_keyword}} /
Key words
ferulic acid /
microdialysis /
probe recovery /
in vivo /
in vitro /
transdermal pharmacokinetics
{{custom_keyword}} /
中图分类号：
R944
R965
{{custom_clc.code}}
({{custom_clc.text}})
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] KREILGAARD M. Assessment of cutaneous drug delivery using microdialysis[J]. Adv Drug Deliv Rev, 2002, 54(suppl 1):S99-121.
[2] SCHMIDT S, BANKS R, KUMAR V, et al. Clinical microdialysis in skin and soft tissues: an update[J]. J Clin Pharmacol, 2008, 48 (3):351-364.
[3] SHANNON R J, CARPENTER K L, GUILFOULE M R, et al. Cerebral microdialysis in clinical studies of drugs: pharmacokinetic applications[J]. J Pharmacokinet Pharmacodyn, 2013, 40 (3):343-358.
[4] PLOCK N, KLOFT C. Microdialysis-theoretical background and recent implementation in applied life-sciences[J]. Eur J Pharm Sci, 2005, 25 (1):1-24.
[5] ZEREDO F J, DALLA C T, DERENDORF H. Role of microdialysis in pharmacokinetics and pharmacodynamics: current status and future directions[J]. Clin Pharmacokinet, 2014, 53 (3):205-212.
[6] KUMAR N, PRUTHI V. Potential applications of ferulic acid from natural sources[J]. Biotechnol Rep(Amst), 2014, 16 (4):86-93.
[7] MATHEW S, ABRAHAM T E. Ferulic acid: an antioxidant found naturally in plant cell walls and feruloyl esterases involved in its release and their applications[J]. Crit Rev Biotechnol, 2004, 24 (2-3):59-83.
[8] ZDUNSKA K, DANA A, KOLODZIEJCZAK A, et al. Antioxidant properties of ferulic acid and its possible application[J]. Skin Pharmacol Physiol, 2018, 31 (6):332-336.
[9] CHEN M, LIU X, FAHR A. Skin delivery of ferulic acid from different vesicular systems[J]. J Biomed Nanotechnol, 2010, 6 (5):577-585.
[10] BUMRUNGPERT A, LILITCHAN S, TUNTIPOPIPAT S, et al. Ferulic acid supplementation improves lipid profiles, oxidative stress, and inflammatory status in hyperlipidemic subjects: a randomized, double-blind, placebo-controlled clinical trial[J]. Nutrients, 2018, 10 (6):713-721.
[11] OU Y Z, PAN L L, TANG J M, et al. Studies on pharmacokinetics of ferulic acid, Rhizoma Chuanxiong and Naodesheng capsule in rat[J]. China J Chin Mater Med (中国中药杂志), 2010, 35 (2):226-228.
[12] MO L L,WANG S J,YANG B K. Permeability of ferulic acid in Caco-2 cell model and its absorption properties in rats in vivo[J]. China Tradit Herb Drugs (中草药), 2012, 43 (5):947-951.
[13] WU R Y, JIN Y, LIU X H, et al. Determination of ferulic acid in rat plasma by LC-MS/MS [J]. Shenyang Pharm Univ(沈阳药科大学学报), 2013, 30 (8):610-614,623.
[14] NAIK A, KALIA Y N, GUY R H. Transdermal drug delivery: overcoming the skin's barrier function[J]. Pharm Sci Technol Today, 2000, 3 (9):318-326.
[15] LAN Y, WANG J Y, TAO Y, et al. Comparison of essential oil from mentha haplocalyx and menthol used as penetration enhancers[J]. China J Chin Mater Med (中国中药杂志), 2016, 41 (8):1516-1522.
[16] WANG D, LIU C S, LIU Y X, et al. Calibration of ferulic acid linear probe in rat skin by microdialysis-high performance liquid chromatography on-line technique[J]. Chin J Pharm Anal(药物分析杂志), 2012, 40 (1):164-168.
[17] LIAO W G, WANG L S, FAN W T, et al. Study on recovery and its influencing factors of ferulic acid and tetramethylpyrazine in cerebral microdialysis probe[J]. China J Chin Mater Med (中国中药杂志), 2015, 40 (21):4275-4280.
[18] BAI J, LU Y, DU S Y, et al. Pharmacokinetics of ferulic acid in transdermal delivery[J]. China J Chin Mater Med (中国中药杂志), 2013, 38 (5):743-747.
[19] BAI J, LU Y, DU S Y, et al. Study on in vitro/in vivo correlation of extracts from Ligusticum Chuanxiong after transdermal administration[J]. China J Chin Mater Med(中国中药杂志), 2013, 38 (3):422-426.
[20] BAI J, LU Y, DU S Y, et al. Preparation and in vitro in vivo evaluation of Chuanxiong Cataplasm[J]. Chin J Tradit Chin Med Pharm(中华中医药杂志), 2013, 28 (5):1259-1266.
[21] CHEN T F, LIU J X, SONG W T, et al. Recovery of ginsenoside Rg1 by brain and blood microdialysis probe in vivo and in vitro[J]. Chin Pharm J (中国药学杂志), 2018, 53 (6):434-438.
[22] ZHANG Y, HE Z F, TANG Z, et al. Microdialysis recovery of oxymatrine in vivo and in vitro[J]. Chin J Tradit Chin Med Pharm (中华中医药杂志), 2015, 30 (9):3108-3111.
[23] ZHANG Y, HE Z F, TANG Z, et al. In vitro and in vivo microdialysis recovery of matrine [J]. Chin Pharm J (中国药学杂志), 2014, 49 (22):2031-2035.
[24] XU H Y, TANG Z, WANG Q, et al. In vitro and in vivo microdialysis recovery of tetramethylpyrazine[J]. Chin Pharm J (中国药学杂志), 2012, 47 (21):1750-1753.
[25] XIA Z F, TANG Z, WANG L, et al. Microdialysis recovery of brimonidine tartrate in vitro and in vivo[J]. Chin Pharm J (中国药学杂志), 2018, 53 (19):1676-1681.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
基金
浙江省神经精神疾病药物研究重点实验室资助(2019E10021)
{{custom_fund}}
PDF(1701 KB)
