溶致液晶在中药新型给药系统中的研究现状、存在问题及其对策
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摘要
溶致液晶(LLC)是由两亲性分子溶于极性溶剂中后相互缔结形成的具有各种几何形状或三维结构的有序体系,通常具有优异的载药适用性、较高的载药量、较好的生物黏附性及透皮促渗性等特点。笔者通过综合分析课题组前期对LLC给药系统的研究经验、成果以及相关研究报道,系统论述了LLC在中药新型给药系统领域,尤其是中药经皮及黏膜给药系统以及中药口服微粒给药系统方面的研究现状、研究价值以及开发潜力。由于目前中药领域LLC研究起步较晚,存在的诸多基础研究问题有待于进一步完善,该文对这些问题进行了归纳总结,并提出了相应研究对策:①基于对单一化学成分LLC的研究方法,结合中药自身特点,进一步加强对中药LLC给药系统的基础研究;②加强中药化学成分释药机制的研究,并进行同步缓释中药LLC给药系统的基础研究;③开发适用于中药的新型LLC材料;④完善中药LLC质量评价体系;⑤探索适用于产业化的LLC制备工艺。
Lyotropic liquid crystal is an ordered system with various geometric shapes or threedimensional structures formed by the interaction of amphiphilic molecules dissolved in polar solvents,and has the characteristics of excellent drug applicability,high drug loading,good bioadhesive property and high transdermal permeability. Through a comprehensive analysis of the research results in this research group and the related research reports of LLC drug delivery system,the authors systematically discussed the research value,development potential and research status of LLC in the field of new drug delivery system of traditional Chinese medicine( TCM),especially in the percutaneous and mucosal drug delivery system and the oral microparticle drug delivery system of TCM. At the same time,due to the current research field of TCM-LLC drug delivery system starts late,many of the basic research problems to be further perfect,this paper had carried on the induction summary to these problems,and put forward the research countermeasures: ①the basic research of TCM-LLC drug delivery system should be strengthened by referencing the research experience and methods of LLC drug delivery system of single chemical component combined with TCM characteristics,②the research on the release mechanism of the chemical components in TCM should be strengthened, and the basic research on the LLC drug delivery system of synchronized sustained release TCM should be carried out,③ development of new LLC materials applicable to TCM,④the quality evaluation system of TCM-LLC should be improved,⑤to explore the LLC preparation process suitable for industrialization.
Lyotropic liquid crystal is an ordered system with various geometric shapes or threedimensional structures formed by the interaction of amphiphilic molecules dissolved in polar solvents,and has the characteristics of excellent drug applicability,high drug loading,good bioadhesive property and high transdermal permeability. Through a comprehensive analysis of the research results in this research group and the related research reports of LLC drug delivery system,the authors systematically discussed the research value,development potential and research status of LLC in the field of new drug delivery system of traditional Chinese medicine( TCM),especially in the percutaneous and mucosal drug delivery system and the oral microparticle drug delivery system of TCM. At the same time,due to the current research field of TCM-LLC drug delivery system starts late,many of the basic research problems to be further perfect,this paper had carried on the induction summary to these problems,and put forward the research countermeasures: ①the basic research of TCM-LLC drug delivery system should be strengthened by referencing the research experience and methods of LLC drug delivery system of single chemical component combined with TCM characteristics,②the research on the release mechanism of the chemical components in TCM should be strengthened, and the basic research on the LLC drug delivery system of synchronized sustained release TCM should be carried out,③ development of new LLC materials applicable to TCM,④the quality evaluation system of TCM-LLC should be improved,⑤to explore the LLC preparation process suitable for industrialization.
引文
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[23]李来存,付萌,陈娟,等.单油酸甘油酯/TPGS/壳聚糖脂质纳米粒提高姜黄素稳定性的研究[J].中南药学,2014,12(5):397-401.
[24] Lesile S B,Puvvada S,Ratna B R,et al. Encapsulation of hemoglobin in a bicontinuous cubic phase lipid[J].Biochim Biophys Acta,1996,1285(2):246-254.
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[26] Nguyen T H,Hanley T,Porter C J,et al. Nanostructured reverse hexagonal liquid crystals sustain plasma concentrations for a poorly water-soluble drug after oral administration[J]. Drug Deliv Transl Re,2011,1(6):429-438.
[27] Nguyen T H,Hanley T,Porter C J,et al. Nanostructured liquid crystalline particles provide long duration sustained-release effect for a poorly water soluble drug after oral administration[J]. J Control Release,2011,153(2):180-186.
[28] Rizwan S B,Assmus D,Boehnke A,et al. Preparation of phytantriol cubosomes by solvent precursor dilution for the delivery of protein vaccines[J]. Eur J Pharm Biopharm,2011,79(1):15-22.
[2] GUO C,WANG J,CAO F,et al. Lyotropic liquid crystal systems in drug delivery[J]. Drug Discov Today,2010,15(23/24):1032-1040.
[3]周艳芳,彭新生.甘油单油酸酯液晶载体材料的体外毒性研究[J].中国医药导报,2010,7(10):22-24.
[4] Rattanapak T,Young K,Rades T,et al. Comparative study of liposomes, transfersomes, ethosomes and cubosomes for transcutaneous immunisation characterisation and in vitro skin penetration[J]. J Pharm Pharmacol,2012,64(11):1560-1569.
[5] Lee J B,Lee D R,Choi N C,et al. Efficient dermal delivery of retinyl palmitate:progressive polarimetry and Raman spectroscopy to evaluate the structure and efficacy[J]. Eur J Pharm Sci,2015,78:111-120.
[6] Bouwstra J A,Honeywell-Nguyen P L,Gooris G S,et al.Structure of the skin barrier and its modulation by vesicular formulations[J]. Prog Lipid Res,2003,42(1):1-36.
[7] ZHANG Y,ZHANG K,GUO T,et al. Transdermal baicalin delivery using diethylene glycol monoethyl ether-mediated cubic phase gel[J]. Int J Pharm,2015,479(1):219-226.
[8]朱娜.丹皮酚脂质立方液晶纳米凝胶载药体系的制备及性能研究[D].蚌埠:蚌埠医学院,2016.
[9]彭新生,周艳芳,韩珂,等.辣椒碱立方液晶纳米粒的制备及体外评价[J].中国中药杂志,2014,39(4):644-647.
[10]李菁,吴卫军,辛洪亮,等.硝酸毛果芸香碱眼用液晶纳米粒的研究[J].成都医学院学报,2013,8(3):257-261.
[11] Salmazi R,Calixto G,Bernegossi J,et al. A curcuminloaded liquid crystal precursor mucoadhesive system for the treatment of vaginal candidiasis[J]. Int J Nanomedicine,2015,10:4815-4824.
[12]崔福德.药剂学[M]. 5版.北京:人民卫生出版社,2004:237-238.
[13] PENG X,WEN X,PAN X,et al. Design and in vitro evaluation of capsaicin transdermal controlled release cubic phase gels[J]. AAPS Pharm Sci Tech,2010,11(3):1405-1410.
[14]吴红兵,霍东风,蒋新国.脂质立方液晶纳米粒作为药物载体的研究进展[J].药学学报,2008,43(5):450-455.
[15]刘丽丽,陈谢谢,陈家乐,等.脂质立方液晶纳米粒的研究进展及其在经皮给药系统中的应用[J].中国药学杂志,2017,52(12):1005-1010.
[16] CHEN Y,MA P,GUI S. Cubic and hexagonal liquid crystals as drug delivery systems[J]. Biomed Res Int,2014,doi:10. 1155/2014/815981.
[17] dos Santos Ramos M A,Calixto G,de Toledo L G,et al.Liquid crystal precursor mucoadhesive system as a strategy to improve the prophylactic action of Syngonanthus nitens(Bong.)Ruhland against infection by Candida krusei[J]. Int J Nanomedicine,2015,doi:10. 2147/IJN. S92638.
[18]郝天云.含单油酸甘油酯的液晶自乳化给药系统[D].南京:中国药科大学,2014.
[19]廉茹月.单油酸甘油酯/泊罗沙姆407立方液晶骨架用于提高水飞蓟素生物利用度的研究[D].上海:复旦大学,2011.
[20]付建武.复方姜黄素脂质立方液晶的制备、表征与评价[D].广州:广州中医药大学,2013.
[21] Jain S,Yadav P,Swami R,et al. Lyotropic liquid crystalline nanoparticles of amphotericin B:implication of phytantriol and glyceryl monooleate on bioavailability enhancement[J]. AAPS Pharm Sci Tech,2018,19(4):1699-1711.
[22]刘承然.长春西汀液晶给药系统的研究[D].南京:中国药科大学,2012.
[23]李来存,付萌,陈娟,等.单油酸甘油酯/TPGS/壳聚糖脂质纳米粒提高姜黄素稳定性的研究[J].中南药学,2014,12(5):397-401.
[24] Lesile S B,Puvvada S,Ratna B R,et al. Encapsulation of hemoglobin in a bicontinuous cubic phase lipid[J].Biochim Biophys Acta,1996,1285(2):246-254.
[25] Lukas B. Lipid-based liquid crystals as drug delivery vehicles for antimicrobial peptides[D]. Gteborg:Chalmers University of Technology,2017.
[26] Nguyen T H,Hanley T,Porter C J,et al. Nanostructured reverse hexagonal liquid crystals sustain plasma concentrations for a poorly water-soluble drug after oral administration[J]. Drug Deliv Transl Re,2011,1(6):429-438.
[27] Nguyen T H,Hanley T,Porter C J,et al. Nanostructured liquid crystalline particles provide long duration sustained-release effect for a poorly water soluble drug after oral administration[J]. J Control Release,2011,153(2):180-186.
[28] Rizwan S B,Assmus D,Boehnke A,et al. Preparation of phytantriol cubosomes by solvent precursor dilution for the delivery of protein vaccines[J]. Eur J Pharm Biopharm,2011,79(1):15-22.