驻极体促进5-氟尿嘧啶体外经皮渗透研究
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- 英文论文题名：In vitro enhancement of transdermal delivery of 5-fluorouracil by electret application
- 论文作者：王春晓 ; 郭鑫 ; 徐立丽 ; 梁媛媛 ; 黄平 ; 崔黎丽 ; 江键
- 英文论文作者：Wang Chunxiao ; Guo Xin ; Xu Lili ; Liang Yuanyuan ; Huang Ping ; Cui Lili ; Jiang Jian ; Department of Physics and mathematics ; Second Military Medical University ; Department of Inorganic Chemistry ; Second Military Medical University
- 年：2015
- 作者机构：第二军医大学基础部数理教研室;第二军医大学药学院无机教研室;
- 论文关键词：驻极体 ; 5-氟尿嘧啶 ; 静电场 ; 透皮给药
- 英文论文关键词：electrets ; 5-fluorouracil ; electrostatic field ; transdermal drug delivery
- 会议召开时间：2015-08-12
- 会议录名称：静电放电：从地面新技术应用到空间卫星安全防护—中国物理学会第二十届全国静电学术会议论文集
- 语种：中文
- 分类号：R943
- 学会代码：WLJD
- 会议名称：静电放电 ; 从地面新技术应用到空间卫星安全防护—中国物理学会第二十届全国静电学术会议
- 会议地点：中国河北石家庄
- 主办单位：中国物理学会静电专业委员会
- 学会名称：中国物理学会静电专业委员会
- 页数：6
- 文件大小：595k
- 原文格式：D
- 会议级别：全国
摘要
本文以±500V、±1000V和±1500V聚丙烯驻极体为促渗源,研究其对5-氟尿嘧啶经离体大鼠皮肤的渗透规律及其在大鼠皮肤内分布的影响,并与未经驻极体作用的对照组进行对比研究。结果显示:1)-1000V和-1500V驻极体作用5-氟尿嘧啶36小时,其累积透皮量均较对照组有显著增加(P<0.05),且负极性驻极体的等效表面电位绝对值越高,药物的经皮渗透量越大。2)1000V和1500V驻极体作用5-氟尿嘧啶36小时,5-氟尿嘧啶的累积透皮量均低于对照组,但滞留在角质层和去角质层皮肤内的药物量显著增加(P<0.05),且随驻极体表面电位增高和作用时间的增加而增加。因此,合理选择驻极体的极性、表面电位和作用时间,有望给增生性瘢痕的治疗提供新方法和新剂型,同时也为皮肤肿瘤的治疗提供新思路。
In this paper,we used±500V、±1000Vand±1500V polypropylene(PP)electrets as physical strategy to study their enhancing effect on in vitro transdermal delivery of 5-fluorouracil(5-Fu)through rat skin and the residual amount of 5-Fu in stratum corneum(SC)and SC stripped rat skin,and the results were compared with those of the control group which was without PP electret application.Our studies indicated that(1)the 36 hours’cumulative penetration amount of 5-Fu through rat skin in vitro after application of-1000V and-1500V PP electrets were significantly increased(P<0.05)with increasing effectively surface potential in absolute value.(2)On the other hand,the 36 hours’cumulative penetration amount of 5-Fu after application of+1000V and+1500V PP electrets were significantly decreased(P<0.05).However,the residual amount of 5-Fu in SC and SC stripped skin were obviously increased(P<0.05)with increasing effective surface potential and application time of the positive electrets.Therefore,the appropriate selection of electrets polarity,magnitude of surface potential and application time might provide a new route for treatment of hypertrophic scar and skin tumors.
In this paper,we used±500V、±1000Vand±1500V polypropylene(PP)electrets as physical strategy to study their enhancing effect on in vitro transdermal delivery of 5-fluorouracil(5-Fu)through rat skin and the residual amount of 5-Fu in stratum corneum(SC)and SC stripped rat skin,and the results were compared with those of the control group which was without PP electret application.Our studies indicated that(1)the 36 hours’cumulative penetration amount of 5-Fu through rat skin in vitro after application of-1000V and-1500V PP electrets were significantly increased(P<0.05)with increasing effectively surface potential in absolute value.(2)On the other hand,the 36 hours’cumulative penetration amount of 5-Fu after application of+1000V and+1500V PP electrets were significantly decreased(P<0.05).However,the residual amount of 5-Fu in SC and SC stripped skin were obviously increased(P<0.05)with increasing effective surface potential and application time of the positive electrets.Therefore,the appropriate selection of electrets polarity,magnitude of surface potential and application time might provide a new route for treatment of hypertrophic scar and skin tumors.
引文
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[2]Profyris C,Tziotzios C,Do Vale I.Cutaneous scarring:Pathophysiology,molecular mechanisms,and scar reduction therapeutics PartⅠ.The molecular basis of scar formation[J].J Am Acad Dermatol.2012,66(1):1-10.
[3]Teot L.The surgical treatment of scars[J].Soins.2013,772:38-40.
[4]Morton LM,Phillips TJ.Wound healing Update[J].Semin Cutan Med Surg.2012,31(1):33-37.
[5]Ohshiro T,Sasaki K.Laser scar management technique[J].Laser Ther.2013,22(4):255-260.
[6]Mounir JH,Kenneth F,James JY,et al.5-fluorouracil treatment of problematic scars[J],Plast Reconstr Surg,2009,123(1):139-148.
[7]Zhang Z,Wo Y,Zhang YX,et al.In vitro study of ethosome penetration in human skin and hypertrophic scar tissue[J].Nanomedicine.2012,8(6):1026-1033.
[8]黄平,石岩,郭鑫,等.正极性驻极体环孢菌素A贴剂的开路热刺激放电[J],高电压技术,2015,41(4):1390-1394。HUANG Ping,SHI Yan,GUO Xin,et al.Open thermally stimulated discharge of positive electret cyclosporine A patch[J],High Voltage Engineering,2015,41(4):1390-1394.
[9]郭鑫,崔黎丽,梁媛媛,等.负极性驻极体环孢菌素A贴剂的压电特性[J],高电压技术,2014,40(6):1916-1920。GUO Xin,CUI Lili,LIANG Yuanyuan,et al.Piezoelectric properties of negative electret cyclosprorine A patch[J],High Voltage Engineering,2014,40(6):1916-1920.
[10]Sessler GM,Electret,Springer Verlag,1987.
[11]Cui LL,Liang YY,Ma L,et al.The combinational effect of PP electret and monlein on transdermal delivery of cyclosporin A in vitro[J],Journal of electrostatics,2013,71:224-227.
[12]Narasimha Murthy S,Shivakumar HN.Topical and transdermal delivery,Handbook of Nov-invasive Drug Delinery System,2010,1-36.
[13]Cui LL,Liu H,Ma L,et al.Enhanecd reansdermal delivery of cyclosporin A by electret and ethyloleate[J],IEEE Transactions on Dielectrics and Electrical Insulation,2012,19(4):1191-1194.
[14]Murthy NS,Boguda VA,Payasada K.Electret enhances transdermal drug pemeation[J].Biophysical Pharmaceutics Bull,2008,31:99-102.
[15]Sylvestre JP,Diaz-Marin C,Delgado-Charro MB,et al.Iontophorese of dexamethasone phosphate:competition with chloride ions[J],JControl Release,2008,131(1):41-46.
[16]Seiji Tokumoto,Naruhito Higo,Kenji Sugibayashi,Effect of elecrtoporation and p H on the iontophoretic transdermal delinery of human insulin[J],Int J Pharm,2006,326(1-2):13-19.
[17]Zhou Cuiping,Liu Yuling,Wang Hongliang,et al.Transdermal delivery of insulin using microneedle rollers in vivo[J],Int J Pharm,2010,392:127-133.
[18]Afendi Dahlan,H Oya Alpar,Paul Stickings,et al.Transutaneous immunisation assisted by low frequenct ultrasound[J],Int J Pharm,2009,368(1-2):123-128.
[19]刘霞,祁兢晶,5-氟尿嘧啶脂质体凝胶剂在兔耳增生性瘢痕中的透皮吸收研究[J],公共卫生与预防医学,2009,20(3):6-8。LIU Xia,HAO Jingjing.In vivo study on diffusion of 5-Fu liposomal gel through hypertrophic scar of rabbit ear model[J],J of Pub Health and Prev Med,2009,20(3):6-8.
[20]Jiang J,Liang YY,Dong FJ,et al.Study of electret effect of rat skin by thermally stimulated discharge analysis[J],Journal of electrostatics,2012,70:258-263.
[21]梁媛媛,江键,程亮,等.负极性聚丙烯驻极体美洛昔康贴剂对大鼠皮肤结构的影响[J].解剖学杂志,2009,32(4):502-505。LIANG Yuanyuan,JIANG Jian,CHENG Liang,et al.Influences of negative polypropylene electret meloxicam patch on percutaneous absorption of drug in rat[J],Chinese Journal of Anatomy,2009,32(4):502-505.
[2]Profyris C,Tziotzios C,Do Vale I.Cutaneous scarring:Pathophysiology,molecular mechanisms,and scar reduction therapeutics PartⅠ.The molecular basis of scar formation[J].J Am Acad Dermatol.2012,66(1):1-10.
[3]Teot L.The surgical treatment of scars[J].Soins.2013,772:38-40.
[4]Morton LM,Phillips TJ.Wound healing Update[J].Semin Cutan Med Surg.2012,31(1):33-37.
[5]Ohshiro T,Sasaki K.Laser scar management technique[J].Laser Ther.2013,22(4):255-260.
[6]Mounir JH,Kenneth F,James JY,et al.5-fluorouracil treatment of problematic scars[J],Plast Reconstr Surg,2009,123(1):139-148.
[7]Zhang Z,Wo Y,Zhang YX,et al.In vitro study of ethosome penetration in human skin and hypertrophic scar tissue[J].Nanomedicine.2012,8(6):1026-1033.
[8]黄平,石岩,郭鑫,等.正极性驻极体环孢菌素A贴剂的开路热刺激放电[J],高电压技术,2015,41(4):1390-1394。HUANG Ping,SHI Yan,GUO Xin,et al.Open thermally stimulated discharge of positive electret cyclosporine A patch[J],High Voltage Engineering,2015,41(4):1390-1394.
[9]郭鑫,崔黎丽,梁媛媛,等.负极性驻极体环孢菌素A贴剂的压电特性[J],高电压技术,2014,40(6):1916-1920。GUO Xin,CUI Lili,LIANG Yuanyuan,et al.Piezoelectric properties of negative electret cyclosprorine A patch[J],High Voltage Engineering,2014,40(6):1916-1920.
[10]Sessler GM,Electret,Springer Verlag,1987.
[11]Cui LL,Liang YY,Ma L,et al.The combinational effect of PP electret and monlein on transdermal delivery of cyclosporin A in vitro[J],Journal of electrostatics,2013,71:224-227.
[12]Narasimha Murthy S,Shivakumar HN.Topical and transdermal delivery,Handbook of Nov-invasive Drug Delinery System,2010,1-36.
[13]Cui LL,Liu H,Ma L,et al.Enhanecd reansdermal delivery of cyclosporin A by electret and ethyloleate[J],IEEE Transactions on Dielectrics and Electrical Insulation,2012,19(4):1191-1194.
[14]Murthy NS,Boguda VA,Payasada K.Electret enhances transdermal drug pemeation[J].Biophysical Pharmaceutics Bull,2008,31:99-102.
[15]Sylvestre JP,Diaz-Marin C,Delgado-Charro MB,et al.Iontophorese of dexamethasone phosphate:competition with chloride ions[J],JControl Release,2008,131(1):41-46.
[16]Seiji Tokumoto,Naruhito Higo,Kenji Sugibayashi,Effect of elecrtoporation and p H on the iontophoretic transdermal delinery of human insulin[J],Int J Pharm,2006,326(1-2):13-19.
[17]Zhou Cuiping,Liu Yuling,Wang Hongliang,et al.Transdermal delivery of insulin using microneedle rollers in vivo[J],Int J Pharm,2010,392:127-133.
[18]Afendi Dahlan,H Oya Alpar,Paul Stickings,et al.Transutaneous immunisation assisted by low frequenct ultrasound[J],Int J Pharm,2009,368(1-2):123-128.
[19]刘霞,祁兢晶,5-氟尿嘧啶脂质体凝胶剂在兔耳增生性瘢痕中的透皮吸收研究[J],公共卫生与预防医学,2009,20(3):6-8。LIU Xia,HAO Jingjing.In vivo study on diffusion of 5-Fu liposomal gel through hypertrophic scar of rabbit ear model[J],J of Pub Health and Prev Med,2009,20(3):6-8.
[20]Jiang J,Liang YY,Dong FJ,et al.Study of electret effect of rat skin by thermally stimulated discharge analysis[J],Journal of electrostatics,2012,70:258-263.
[21]梁媛媛,江键,程亮,等.负极性聚丙烯驻极体美洛昔康贴剂对大鼠皮肤结构的影响[J].解剖学杂志,2009,32(4):502-505。LIANG Yuanyuan,JIANG Jian,CHENG Liang,et al.Influences of negative polypropylene electret meloxicam patch on percutaneous absorption of drug in rat[J],Chinese Journal of Anatomy,2009,32(4):502-505.