载有穿心莲内酯的微乳液和纳米乳液制剂——改善“苦味之王”的生物利用度、靶组织分布及功效
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摘要
穿心莲内酯(AG)为爵床科植物穿心莲(Andrographis paniculata)的特征性成分。该植物为亚洲著名药用植物,在印度、中国和泰国得到广泛使用。《中华人民共和国药典》(简称《中国药典》)收载了中药穿心莲的药材标准,记载这种草药的煎剂可"清热、解毒、消肿"。穿心莲具有众多潜在活性,从抗炎到抗糖尿病作用,从神经保护到抗肿瘤活性,从保肝到抗肥胖特性。然而,AG的生物利用度较低、水溶性较差,因此限制了给药后在体内的分布和积累。此外,AG在胃肠道碱性和酸性环境中不稳定,据报道其半衰期极为短暂。在为提高AG的水溶性和渗透性而采取的各种策略中,技术途径是开发适合的给药系统最有用的方法。本文综述了与载有AG的微粒(MP)和纳米颗粒(NP)相关的已有研究工作。目前已开发出基于聚乳酸-羟基乙酸(PLGA)、海藻酸和葡聚糖衍生物的微粒,分别用于肠胃外口服和肺部给药。NP包括囊泡(脂质体和类脂质体)、聚合NP(基于聚乙烯醇、聚合苯基硼酸、PLGA、人血清白蛋白、聚氰基丙烯酸乙酯和聚合物胶束)、固体脂质NP、微乳液(ME)和纳米乳液(NE)、黄金NP、纳米晶体和纳米混悬液。据报道,所述载有AG的给药系统的生物利用度、靶组织分布和功效都得到了优化。
Andrographolide(AG) is the characteristic constituent of Andrographis paniculata, of the Acanthaceae family. This plant is a well-known Asian medicinal plant that is widely used in India, China, and Thailand. A monograph of Herba Andrographidis(Chuanxinlian) is included in the Chinese Pharmacopoeia, which reports that this decoction can ‘‘remove heat, counteract toxicity, and reduce swellings." The numerous potential activities of AG range from anti-inflammatory to anti-diabetic action,from neuroprotection to antitumor activity, and from hepatoprotective to anti-obesity properties.However, AG has low bioavailability and poor water solubility, which can limit its distribution and accumulation in the body after administration. In addition, AG is not stable in gastrointestinal alkaline and acidic environments, and has been reported to have a very short half-life. Among the diverse strategies that have been adopted to increase AG water solubility and permeability, the technological approach is the most useful way to develop appropriate delivery systems. This review reports on published studies related to microparticles(MPs) and nanoparticles(NPs) loaded with AG. MPs based on polylactic-glycolic acid(PLGA), alginic acid, and glucan derivatives have been developed for parenteral oral and pulmonary administration, respectively. NPs include vesicles(both liposomes and niosomes);polymeric NPs(based on polyvinyl alcohol, polymerized phenylboronic acid, PLGA, human serum albumin, poly ethylcyanoacrylate, and polymeric micelles); solid lipid NPs; microemulsions and nanoemulsions; gold NPs; nanocrystals; and nanosuspensions. Improved bioavailability, target-tissue distribution, and efficacy of AG loaded in the described drug delivery systems have been reported.
Andrographolide(AG) is the characteristic constituent of Andrographis paniculata, of the Acanthaceae family. This plant is a well-known Asian medicinal plant that is widely used in India, China, and Thailand. A monograph of Herba Andrographidis(Chuanxinlian) is included in the Chinese Pharmacopoeia, which reports that this decoction can ‘‘remove heat, counteract toxicity, and reduce swellings." The numerous potential activities of AG range from anti-inflammatory to anti-diabetic action,from neuroprotection to antitumor activity, and from hepatoprotective to anti-obesity properties.However, AG has low bioavailability and poor water solubility, which can limit its distribution and accumulation in the body after administration. In addition, AG is not stable in gastrointestinal alkaline and acidic environments, and has been reported to have a very short half-life. Among the diverse strategies that have been adopted to increase AG water solubility and permeability, the technological approach is the most useful way to develop appropriate delivery systems. This review reports on published studies related to microparticles(MPs) and nanoparticles(NPs) loaded with AG. MPs based on polylactic-glycolic acid(PLGA), alginic acid, and glucan derivatives have been developed for parenteral oral and pulmonary administration, respectively. NPs include vesicles(both liposomes and niosomes);polymeric NPs(based on polyvinyl alcohol, polymerized phenylboronic acid, PLGA, human serum albumin, poly ethylcyanoacrylate, and polymeric micelles); solid lipid NPs; microemulsions and nanoemulsions; gold NPs; nanocrystals; and nanosuspensions. Improved bioavailability, target-tissue distribution, and efficacy of AG loaded in the described drug delivery systems have been reported.
引文
[1]Thamlikitkul V,Dechatiwongse T,Theerapong S,Chantrakul C,Boonroj P,Punkrut W,et al.Efficacy of Andrographis paniculata,Nees for pharyngotonsillitis in adults.J Med Assoc Thai 1991;74(10):437-42.
[2]Poolsup N,Suthisisang C,Prathanturarug S,Asawamekin A,Chanchareon U.Andrographis paniculata in the symptomatic treatment of uncomplicated upper respiratory tract infection:systematic review of randomized controlled trials.JClin Pharm Ther 2004;29(1):37-45.
[3]Saxena RC,Singh R,Kumar P,Yadav SC,Negi MPS,Saxena VS,et al.Arandomized double blind placebo controlled clinical evaluation of extract of Andrographis paniculata(KalmColdTM)in patients with uncomplicated upper respiratory tract infection.Phytomedicine 2010;17(3-4):178-85.
[4]Chinese Pharmacopoeia Commission,editor.Pharmacopoeia of the People’s Republic of China.Beijing:China Medical Science Press;2015.
[5]Ganguly M,Manna A,Chandra G,Ghosh D,Ghosh LK,Gupta BK.Andrographis paniculata:a promising herbal plant.Ind J Pharm Edu 2001;35(2):63-4.
[6]Panossian A,Wikman G.Efficacy of Andrographis paniculata in upper respiratory tract infectious diseases and the mechanism of action.In:Wagner H,Ulrich-Merzenich G,editors.Evidence and rational based research on Chinese drugs.Vienna:Springer;2013.p.137-79.
[7]Andrographidis Herba.In:World Health Organization.WHO monographs on selected medicinal plants.Geneva:World Health Organization;2004.p.12-24.
[8]Karioti A,Timoteo P,Bergonzi MC,Bilia AR.A validated method for the quality control of Andrographis paniculata preparations.Planta Med 2017;83(14-15):1207-13.
[9]Dai Y,Chen SR,Chai L,Zhao J,Wang Y,Wang Y.Overview of pharmacological activities of Andrographis paniculata and its major compound andrographolide.Crit Rev Food Sci Nutr.Epub 2018 Sep 10.
[10]Guccione C,Oufir M,Piazzini V,Eigenmann DE,J?hne EA,Zabela V,et al.Andrographolide-loaded nanoparticles for brain delivery:formulation,characterisation and in vitro permeability using hCMEC/D3 cell line.Eur JPharm Biopharm 2017;119:253-63.
[11]Jiang Y,Wang F,Xu H,Liu H,Meng Q,Liu W.Development of andrographolide loaded PLGA microspheres:optimization,characterization and in vitro-in vivo correlation.Int J Pharm 2014;475(1-2):475-84.
[12]Shariff A,Manna PK,Paranjothy KLK,Manjula M.Entrapment of andrographolide in cross-linked alginate pellets:I.formulation and evaluation of associated release kinetics.Pak J Pharm Sci 2007;20(1):1-9.
[13]Shariff A,Manna PK,Paranjothy KLK,Manjula M.Entrapment of andrographolide in cross-linked alginate pellets:II.physicochemical characterization to study the pelletization of andrographolide.Pak J Pharm Sci 2007;20(1):9-15.
[14]Mali AJ,Bothiraja C,Purohit RN,Pawar AP.In vitro and in vivo performance of novel spray dried andrographolide loaded scleroglucan based formulation for dry powder inhaler.Curr Drug Deliv 2017;14(7):968-80.
[15]Bilia AR,Piazzini V,Guccione C,Risaliti L,Asprea M,Capecchi G,et al.Improving on nature:the role of nanomedicine in the development of clinical natural drugs.Planta Med 2017;83(5):366-81.
[16]Roy P,Das S,Mondal A,Chatterji U,Mukherjee A.Nanoparticle engineering enhances anticancer efficacy of andrographolide in MCF-7 cells and mice bearing EAC.Curr Pharm Biotechnol 2012;13(15):2669-81.
[17]Kim J,Lee J,Lee YM,Pramanick S,Im S,Kim WJ.Andrographolide-loaded polymerized phenylboronic acid nanoconstruct for stimuli-responsive chemotherapy.J Control Release 2017;259:203-11.
[18]Roy P,Das S,Bera T,Mondol S,Mukherjee A.Andrographolide nanoparticles in leishmaniasis:characterization and in vitro evaluations.Int J Nanomed2010;5:1113-21.
[19]Roy P,Das S,Auddy RG,Mukherjee A.Engineered andrographolide nanosystems for smart recovery in hepatotoxic conditions.Int J Nanomed2014;9:4723-35.
[20]Das S,Pradhan GK,Das S,Nath D,Das Saha K.Enhanced protective activity of nano formulated andrographolide against arsenic induced liver damage.Chem Biol Interact 2015;242:281-9.
[21]Chellampillai B,Pawar AP.Improved bioavailability of orally administered andrographolide from pH-sensitive nanoparticles.Eur J Drug Metab Ph2011;35(3-4):123-9.
[22]Zhang J,Li Y,Gao W,Repka MA,Wang Y,Chen M.Andrographolide-loaded PLGA-PEG-PLGA micelles to improve its bioavailability and anticancer efficacy.Expert Opin Drug Deliv 2014;11(9):1367-80.Erratum in:Expert Opin Drug Deliv 2015;12(4):689.
[23]Yao H,Song S,Miao X,Liu X,Zhao J,Wang Z,et al.mPEG-PLA micelle for delivery of effective parts of Andrographis Paniculata.Curr Drug Deliv 2018;15(4):532-40.
[24]Bilia AR,Bergonzi MC,Guccione C,Manconi M,Fadda AM,Sinico C.Vesicles and micelles:two versatile vectors for the delivery of natural products.J Drug Deliv Sci Tec 2016;32(Pt B):241-55.
[25]Kang X,Zheng Z,Liu Z,Wang H,Zhao Y,Zhang W,et al.Liposomal codelivery of doxorubicin and andrographolide inhibits breast cancer growth and metastasis.Mol Pharmaceut 2018;15(4):1618-26.
[26]Tu YS,Sun DM,Zhang JJ,Jiang ZQ,Chen YX,Zeng XH,et al.Preparation and characterisation of andrographolide niosomes and its anti-hepatocellular carcinoma activity.J Microencapsul 2014;31(4):307-16.
[27]Jain PK,Khurana N,Pounikar Y,Gajbhiye A,Kharya MD.Enhancement of absorption and hepatoprotective potential through soya-phosphatidylcholineandrographolide vesicular system.J Liposome Res 2013;23(2):110-8.
[28]Maiti K,Mukherjee K,Murugan V,Saha BP,Mukherjee PK.Enhancing bioavailability and hepatoprotective activity of andrographolide from Andrographis paniculata,a well-known medicinal food,through its herbosome.J Sci Food Agric 2010;90(1):43-51.
[29]Sinha J,Mukhopadhyay S,Das N,Basu MK.Targeting of liposomal andrographolide to L.donovani-infected macrophages in vivo.Drug Deliv2000;7(4):209-13.
[30]Li M,Zhang T,Zhu L,Wang R,Jin Y.Liposomal andrographolide dry powder inhalers for treatment of bacterial pneumonia via anti-inflammatory pathway.Int J Pharm 2017;528(1-2):163-71.
[31]Piazzini V,Landucci E,Graverini G,Pellegrini-Giampietro DE,Bilia AR,Bergonzi MC.Stealth and cationic nanoliposomes as drug delivery systems to increase andrographolide BBB permeability.Pharmaceutics 2018;10(3):128.
[32]Parveen R,Ahmad FJ,Iqbal Z,Samim M,Ahmad S.Solid lipid nanoparticles of anticancer drug andrographolide:formulation,in vitro and in vivo studies.Drug Dev Ind Pharm 2014;40(9):1206-12.
[33]Yang T,Sheng HH,Feng NP,Wei H,Wang ZT,Wang CH.Preparation of andrographolide-loaded solid lipid nanoparticles and their in vitro and in vivo evaluations:characteristics,release,absorption,transports,pharmacokinetics,and antihyperlipidemic activity.J Pharm Sci 2013;102(12):4414-25.
[34]Graverini G,Piazzini V,Landucci E,Pantano D,Nardiello P,Casamenti F,et al.Solid lipid nanoparticles for delivery of andrographolide across the bloodbrain barrier:in vitro and in vivo evaluation.Colloid Surface B2018;161:302-13.
[35]McClements DJ.Nanoemulsions versus microemulsions:terminology,differences,and similarities.Soft Matter 2012;8(6):1719-29.
[36]Yen CC,Chen YC,Wu MT,Wang CC,Wu YT.Nanoemulsion as a strategy for improving the oral bioavailability and anti-inflammatory activity of andrographolide.Int J Nanomed 2018;13:669-80.
[37]Du H,Yang X,Li H,Han L,Li X,Dong X,et al.Preparation and evaluation of andrographolide-loaded microemulsion.J Microencapsul 2012;29(7):657-65.
[38]Mishra N,Yadav KS,Rai VK,Yadav NP.Polysaccharide encrusted multilayered nano-colloidal system of andrographolide for improved hepatoprotection.AAPS PharmSciTech 2017;18(2):381-92.
[39]Kim CK,Ghosh P,Rotello VM.Multimodal drug delivery using gold nanoparticles.Nanoscale 2009;1(1):61-7.
[40]Das S,Halder A,Mandal S,Mazumder MAJ,Bera T,Mukherjee A,et al.Andrographolide engineered gold nanoparticle to overcome drug resistant visceral leishmaniasis.Artif Cells Nanomed Biotechnol.Epub 2018 Feb 8.
[41]Ma Y,Yang Y,Xie J,Xu J,Yue P,Yang M.Novel nanocrystal-based solid dispersion with high drug loading,enhanced dissolution,and bioavailability of andrographolide.Int J Nanomed 2018;13:3763-79.
[42]Xu J,Ma Y,Xie Y,Chen Y,Liu Y,Yue P,et al.Design and evaluation of novel solid self-nanodispersion delivery system for andrographolide.AAPSPharmSciTech 2017;18(5):1572-84.
[43]Chen Y,Liu Y,Xu J,Xie Y,Zheng Q,Yue P,et al.A natural triterpenoid saponin as multifunctional stabilizer for drug nanosuspension powder.AAPSPharmSciTech 2017;18(7):2744-53.
[44]Qiao H,Chen L,Rui T,Wang J,Chen T,Fu T,et al.Fabrication and in vitro/in vivo evaluation of amorphous andrographolide nanosuspensions stabilized by D-atocopheryl polyethylene glycol 1000 succinate/sodium lauryl sulfate.Int JNanomed 2017;12:1033-46.
[45]Guo L,Kang L,Liu X,Lin X,Di D,Wu Y,et al.A novel nanosuspension of andrographolide:preparation,characterization and passive liver target evaluation in rats.Eur J Pharm Sci 2017;104:13-22.
[2]Poolsup N,Suthisisang C,Prathanturarug S,Asawamekin A,Chanchareon U.Andrographis paniculata in the symptomatic treatment of uncomplicated upper respiratory tract infection:systematic review of randomized controlled trials.JClin Pharm Ther 2004;29(1):37-45.
[3]Saxena RC,Singh R,Kumar P,Yadav SC,Negi MPS,Saxena VS,et al.Arandomized double blind placebo controlled clinical evaluation of extract of Andrographis paniculata(KalmColdTM)in patients with uncomplicated upper respiratory tract infection.Phytomedicine 2010;17(3-4):178-85.
[4]Chinese Pharmacopoeia Commission,editor.Pharmacopoeia of the People’s Republic of China.Beijing:China Medical Science Press;2015.
[5]Ganguly M,Manna A,Chandra G,Ghosh D,Ghosh LK,Gupta BK.Andrographis paniculata:a promising herbal plant.Ind J Pharm Edu 2001;35(2):63-4.
[6]Panossian A,Wikman G.Efficacy of Andrographis paniculata in upper respiratory tract infectious diseases and the mechanism of action.In:Wagner H,Ulrich-Merzenich G,editors.Evidence and rational based research on Chinese drugs.Vienna:Springer;2013.p.137-79.
[7]Andrographidis Herba.In:World Health Organization.WHO monographs on selected medicinal plants.Geneva:World Health Organization;2004.p.12-24.
[8]Karioti A,Timoteo P,Bergonzi MC,Bilia AR.A validated method for the quality control of Andrographis paniculata preparations.Planta Med 2017;83(14-15):1207-13.
[9]Dai Y,Chen SR,Chai L,Zhao J,Wang Y,Wang Y.Overview of pharmacological activities of Andrographis paniculata and its major compound andrographolide.Crit Rev Food Sci Nutr.Epub 2018 Sep 10.
[10]Guccione C,Oufir M,Piazzini V,Eigenmann DE,J?hne EA,Zabela V,et al.Andrographolide-loaded nanoparticles for brain delivery:formulation,characterisation and in vitro permeability using hCMEC/D3 cell line.Eur JPharm Biopharm 2017;119:253-63.
[11]Jiang Y,Wang F,Xu H,Liu H,Meng Q,Liu W.Development of andrographolide loaded PLGA microspheres:optimization,characterization and in vitro-in vivo correlation.Int J Pharm 2014;475(1-2):475-84.
[12]Shariff A,Manna PK,Paranjothy KLK,Manjula M.Entrapment of andrographolide in cross-linked alginate pellets:I.formulation and evaluation of associated release kinetics.Pak J Pharm Sci 2007;20(1):1-9.
[13]Shariff A,Manna PK,Paranjothy KLK,Manjula M.Entrapment of andrographolide in cross-linked alginate pellets:II.physicochemical characterization to study the pelletization of andrographolide.Pak J Pharm Sci 2007;20(1):9-15.
[14]Mali AJ,Bothiraja C,Purohit RN,Pawar AP.In vitro and in vivo performance of novel spray dried andrographolide loaded scleroglucan based formulation for dry powder inhaler.Curr Drug Deliv 2017;14(7):968-80.
[15]Bilia AR,Piazzini V,Guccione C,Risaliti L,Asprea M,Capecchi G,et al.Improving on nature:the role of nanomedicine in the development of clinical natural drugs.Planta Med 2017;83(5):366-81.
[16]Roy P,Das S,Mondal A,Chatterji U,Mukherjee A.Nanoparticle engineering enhances anticancer efficacy of andrographolide in MCF-7 cells and mice bearing EAC.Curr Pharm Biotechnol 2012;13(15):2669-81.
[17]Kim J,Lee J,Lee YM,Pramanick S,Im S,Kim WJ.Andrographolide-loaded polymerized phenylboronic acid nanoconstruct for stimuli-responsive chemotherapy.J Control Release 2017;259:203-11.
[18]Roy P,Das S,Bera T,Mondol S,Mukherjee A.Andrographolide nanoparticles in leishmaniasis:characterization and in vitro evaluations.Int J Nanomed2010;5:1113-21.
[19]Roy P,Das S,Auddy RG,Mukherjee A.Engineered andrographolide nanosystems for smart recovery in hepatotoxic conditions.Int J Nanomed2014;9:4723-35.
[20]Das S,Pradhan GK,Das S,Nath D,Das Saha K.Enhanced protective activity of nano formulated andrographolide against arsenic induced liver damage.Chem Biol Interact 2015;242:281-9.
[21]Chellampillai B,Pawar AP.Improved bioavailability of orally administered andrographolide from pH-sensitive nanoparticles.Eur J Drug Metab Ph2011;35(3-4):123-9.
[22]Zhang J,Li Y,Gao W,Repka MA,Wang Y,Chen M.Andrographolide-loaded PLGA-PEG-PLGA micelles to improve its bioavailability and anticancer efficacy.Expert Opin Drug Deliv 2014;11(9):1367-80.Erratum in:Expert Opin Drug Deliv 2015;12(4):689.
[23]Yao H,Song S,Miao X,Liu X,Zhao J,Wang Z,et al.mPEG-PLA micelle for delivery of effective parts of Andrographis Paniculata.Curr Drug Deliv 2018;15(4):532-40.
[24]Bilia AR,Bergonzi MC,Guccione C,Manconi M,Fadda AM,Sinico C.Vesicles and micelles:two versatile vectors for the delivery of natural products.J Drug Deliv Sci Tec 2016;32(Pt B):241-55.
[25]Kang X,Zheng Z,Liu Z,Wang H,Zhao Y,Zhang W,et al.Liposomal codelivery of doxorubicin and andrographolide inhibits breast cancer growth and metastasis.Mol Pharmaceut 2018;15(4):1618-26.
[26]Tu YS,Sun DM,Zhang JJ,Jiang ZQ,Chen YX,Zeng XH,et al.Preparation and characterisation of andrographolide niosomes and its anti-hepatocellular carcinoma activity.J Microencapsul 2014;31(4):307-16.
[27]Jain PK,Khurana N,Pounikar Y,Gajbhiye A,Kharya MD.Enhancement of absorption and hepatoprotective potential through soya-phosphatidylcholineandrographolide vesicular system.J Liposome Res 2013;23(2):110-8.
[28]Maiti K,Mukherjee K,Murugan V,Saha BP,Mukherjee PK.Enhancing bioavailability and hepatoprotective activity of andrographolide from Andrographis paniculata,a well-known medicinal food,through its herbosome.J Sci Food Agric 2010;90(1):43-51.
[29]Sinha J,Mukhopadhyay S,Das N,Basu MK.Targeting of liposomal andrographolide to L.donovani-infected macrophages in vivo.Drug Deliv2000;7(4):209-13.
[30]Li M,Zhang T,Zhu L,Wang R,Jin Y.Liposomal andrographolide dry powder inhalers for treatment of bacterial pneumonia via anti-inflammatory pathway.Int J Pharm 2017;528(1-2):163-71.
[31]Piazzini V,Landucci E,Graverini G,Pellegrini-Giampietro DE,Bilia AR,Bergonzi MC.Stealth and cationic nanoliposomes as drug delivery systems to increase andrographolide BBB permeability.Pharmaceutics 2018;10(3):128.
[32]Parveen R,Ahmad FJ,Iqbal Z,Samim M,Ahmad S.Solid lipid nanoparticles of anticancer drug andrographolide:formulation,in vitro and in vivo studies.Drug Dev Ind Pharm 2014;40(9):1206-12.
[33]Yang T,Sheng HH,Feng NP,Wei H,Wang ZT,Wang CH.Preparation of andrographolide-loaded solid lipid nanoparticles and their in vitro and in vivo evaluations:characteristics,release,absorption,transports,pharmacokinetics,and antihyperlipidemic activity.J Pharm Sci 2013;102(12):4414-25.
[34]Graverini G,Piazzini V,Landucci E,Pantano D,Nardiello P,Casamenti F,et al.Solid lipid nanoparticles for delivery of andrographolide across the bloodbrain barrier:in vitro and in vivo evaluation.Colloid Surface B2018;161:302-13.
[35]McClements DJ.Nanoemulsions versus microemulsions:terminology,differences,and similarities.Soft Matter 2012;8(6):1719-29.
[36]Yen CC,Chen YC,Wu MT,Wang CC,Wu YT.Nanoemulsion as a strategy for improving the oral bioavailability and anti-inflammatory activity of andrographolide.Int J Nanomed 2018;13:669-80.
[37]Du H,Yang X,Li H,Han L,Li X,Dong X,et al.Preparation and evaluation of andrographolide-loaded microemulsion.J Microencapsul 2012;29(7):657-65.
[38]Mishra N,Yadav KS,Rai VK,Yadav NP.Polysaccharide encrusted multilayered nano-colloidal system of andrographolide for improved hepatoprotection.AAPS PharmSciTech 2017;18(2):381-92.
[39]Kim CK,Ghosh P,Rotello VM.Multimodal drug delivery using gold nanoparticles.Nanoscale 2009;1(1):61-7.
[40]Das S,Halder A,Mandal S,Mazumder MAJ,Bera T,Mukherjee A,et al.Andrographolide engineered gold nanoparticle to overcome drug resistant visceral leishmaniasis.Artif Cells Nanomed Biotechnol.Epub 2018 Feb 8.
[41]Ma Y,Yang Y,Xie J,Xu J,Yue P,Yang M.Novel nanocrystal-based solid dispersion with high drug loading,enhanced dissolution,and bioavailability of andrographolide.Int J Nanomed 2018;13:3763-79.
[42]Xu J,Ma Y,Xie Y,Chen Y,Liu Y,Yue P,et al.Design and evaluation of novel solid self-nanodispersion delivery system for andrographolide.AAPSPharmSciTech 2017;18(5):1572-84.
[43]Chen Y,Liu Y,Xu J,Xie Y,Zheng Q,Yue P,et al.A natural triterpenoid saponin as multifunctional stabilizer for drug nanosuspension powder.AAPSPharmSciTech 2017;18(7):2744-53.
[44]Qiao H,Chen L,Rui T,Wang J,Chen T,Fu T,et al.Fabrication and in vitro/in vivo evaluation of amorphous andrographolide nanosuspensions stabilized by D-atocopheryl polyethylene glycol 1000 succinate/sodium lauryl sulfate.Int JNanomed 2017;12:1033-46.
[45]Guo L,Kang L,Liu X,Lin X,Di D,Wu Y,et al.A novel nanosuspension of andrographolide:preparation,characterization and passive liver target evaluation in rats.Eur J Pharm Sci 2017;104:13-22.