胰岛素鼻黏膜给药系统的研究进展Progress of the intranasal administration of insulin
李莹,段晓品,毛世瑞
LI Ying,DUAN Xiao-pin,MAO Shi-rui(School of Pharmacy
摘要(Abstract):
目的综述胰岛素近年来鼻黏膜给药的相关信息。方法查阅国内外相关文献36篇,进行相关分析、归纳和总结。结果综述出鼻黏膜给药的特点以及提高鼻黏膜生物利用度的诸多方法。在胰岛素制剂中加入安全高效的吸收促进剂或水不溶性粉末将会很大程度上提高其生物利用度。结论胰岛素鼻黏膜给药在药学领域将会有广阔的发展前景。
Objective To review the new administration routes of insulin and the development of intranasal delivery system.Methods According to thirty-six recent relevant literatures,the new routes and the development of intranasal delivery system of insulin were summarized.The new routes of insulin administration,the characteristics of intranasal delivery and some strategies to improve the bioavailability of insulin after nasal administration were summarized.Results It seems that the addition of safe absorption enhancers or water-insoluble powders into insulin formulation can dramatically improve the bioavailability of insulin after nasal administration.Conclusions The intranasal administration of insulin in the pharmaceutical field is promising.
关键词(KeyWords):
胰岛素;鼻黏膜给药;吸收促进剂;水不溶性粉末
insulin;intranasal administration;absorption enhancer;water-insoluble powder
基金项目(Foundation):
作者(Author):
李莹,段晓品,毛世瑞
LI Ying,DUAN Xiao-pin,MAO Shi-rui(School of Pharmacy
DOI: 10.14066/j.cnki.cn21-1349/r.2012.04.015
参考文献(References):
- [1]DUAN Xiao-pin,MAO Shi-rui.New strategies to im-prove the intranasal absorption of insulin[J].DrugDiscovery Today,2010,15(11-12):417-427.
- [2]李肖玲,安富荣,陆国红.胰岛素肺部给药系统研究进展[J].中国现代应用药学,2008,(1):609-613.
- [3]HENKIN R I.Inhaled insulin Intrapulmonary,in-tranasal,and other routes of administration:Mecha-nisms of action[J].Nutrition,2010,26(1):33-39.
- [4]毛世瑞,杨宏图,毕殿洲.提高药物鼻黏膜吸收的途径[J].中国药学杂志,1998,33(11):641-645.
- [5]梁文权.生物药剂学与药物动力学:第2版[M].北京:人民卫生出版社,2004:71-72.
- [6]SHECHTER Y,MIRONCHIK M,RUBINRAUT S,etal.Reversible pegylation of insulin facilitates its pro-longed action in vivo[J].European Journal of Pharma-ceutics and Biopharmaceutics,2008,70(1):19-28.
- [7]AGARWAL V,REDDY I K,KHAN M A.Polymethyac-rylate based microparticulates of insulin for oral deliv-ery:Preparation and in vitro dissolution stability in thepresence of enzyme inhibitors[J].International Journalof Pharmaceutics,2001,225(1-2):31-39.
- [8]SIMON M,WITTMAR M,KISSEL T,et al.Insulin con-taining nanocomplexes formed by self-assembly frombiodegradable amine-modified poly(vinyl alcohol)-graft-poly(L-lactide):bioavailability and nasal tolera-bility in rats[J].Pharmaceutical Research,2005,22(11):1879-1885.
- [9]ZHANG Xin-ge,ZHANG Hui-jie,WU Zhong-ming etal.Nasal absorption enhancement of insulin using PEG-grafted chitosan nanoparticles[J].European Journal ofPharmaceutics and Biopharmaceutics,2008,68(3):526-534.
- [10]MAO Shi-rui,GERMERSHAUS O,FISCHER D,et al.Uptake and transport of PEG-graft-trimethyl-chitosan-copolymer-insulin nanocomplexes by epithelial cells[J].Pharmaceutical Research,2005,22(12):2058-2068.
- [11]DYER A M,HINCHCLIFFE M,WATTS P,et al.Nasaldelivery of insulin using novel chitosan based formula-tions:a comparative study in two animal models be-tween simple chitosan formulations and chitosan nanop-articles[J].Pharmaceutical Research,2002,19(7):998-1008.
- [12]VLLASALIU D,EXPOSITO H R,HERAS A,et al.Tight junction modulation by chitosan nanoparticles:Comparison with chitosan solution[J].InternationalJournal of Pharmaceutics,2010,400(1-2):183-193.
- [13]VARSHOSAZ J,SADRAI H,ALINAGARI R.Nasaldelivery of insulin using chitosan microspheres[J].Journal of Microencapsulation,2004,21(7):761-774.
- [14]SINTOV A C,LEVY H V,BOTNER S.Systemicdelivery of insulin via the nasal route using a new mi-croemulsion system:In vitro and in vivo studies[J].Journal of Controlled Release,2010,148(1):168-176.
- [15]MEI Dan,MAO Shi-rui.Effect of chitosan structureproperties and molecular weight on the intranasal ab-sorption of tetramethylpyrazine phosphate in rats[J].European Journal of Pharmaceutics and Biopharmaceu-tics,2008,70(3):874-881.
- [16]CALLENS C,REMON J P.Evaluation of starch-malto-dextrin-Carbopol 974 P mixtures for the nasal deliveryof insulin in rabbits[J].Journal of Control Release,2000,66(2-3):215-220.
- [17]D’SOUZA R,MUTALIK S,VENKATESH M,et al.In-sulin gel as an alternate to parenteral insulin:Formula-tion,preclinical,and clinical studies[J].AAPS Pharm-SciTech,2005,6(2):E184-E189.
- [18]WU Jie,WEI Wei,WANG Lian-yan,et al.A thermo-sensitive hydrogel based on quaternized chitosan andpoly(ethylene glycol)for nasal drug delivery system[J].Biomaterials,2007,28(13):2220-2232.
- [19]CHUNG Tze-wen,LIU Der-zen,YANG Juin-sen.Effects of interpenetration of thermo-sensitive gels bycrosslinking of chitosan on nasal delivery of insulin:Invitro characterization and in vivo study[J].Carbohy-drate Polymers,2010,82(2):316-322.
- [20]MORIMOTO K,YAMAGUCHI H,IWAKURA Y,etal.Effects of viscous hyaluronate-sodium solutions onthe nasal absorption of vasopressin and an analogue[J].Pharmaceutical Research,1991,8(4):471-474.
- [21]HORVAT S,FEHER A,WOLBURG H,et al.Sodiumhyaluronate as a mucoadhesive component in nasal for-mulation enhances delivery of molecules to brain tissue[J].European Journal of Pharmaceutics and Biophar-maceutics,2009,72(1):252-259.
- [22]HUH Y,CHO H J,YOON I-S,et al.Preparation and e-valuation of spray-dried hyaluronic acid microspheresfor intranasal delivery of fexofenadine hydrochloride[J].European Journal of Pharmaceutical Sciences,2010,40(1):9-15.
- [23]ISHIKAWA F,MURANO M,HIRAISHI M,et al.Insol-uble powder formulation as an effective nasal drug de-livery system[J].Pharmaceutical Research,2002,19(8):1097-1104.
- [24]ISHIKAWA F,KATSURA M,TAMAI I,et al.Improvednasal bioavailability of elcatonin by insoluble powderformulation[J].International Journal of Pharmaceu-tics,2001,224(1-2):105-114.
- [25]MATSUYAMA T,MORITA T,HORIKIRI Y,et al.Influence of fillers in powder formulations containingN-acetyl-L-cysteine on nasal peptide absorption[J].Journal of Controlled Release,2007,120(1-2):88-94.
- [26]YU Shao-yun,ZHAO Ying,WU Feng-lan,et al.Nasalinsulin delivery in the chitosan solution:in vitro and invivo studies[J].International Journal of Pharmaceu-tics,2004,281(1-2):11-23.
- [27]SOANE R J,HINCHCLIFFE M,DAVIS S S,et al.Clearance characteristics of chitosan based formulationsin the sheep nasal cavity[J].International Journal ofPharmaceutics,2001,217(1-2):183-191.
- [28]PLESSIS L H,LUBBE J,STRAUSSET T,et al.En-hancement of nasal and intestinal calcitonin delivery bythe novel Pheroid TM fatty acid based delivery systemand by N-trimethyl chitosan chloride[J].InternationalJournal of Pharmaceutics,2010,385(1-2):181-186.
- [29]ZHANG Xue-jiao,ZHANG Xin-ge,WU Zhong-ming,et al.β-Cyclodextrin grafting hyperbranchedpolyglycerols as carriers for nasal insulin delivery[J].Carbohydrate Polymers,2011,84(2):1419-1425.
- [30]AGU R U,JORIISSEN M,WILLEMS T,et al.Safetyassessment of selected cyclodextrins-effect onciliary ac-tivity using a human cell suspension culture model ex-hibiting in vitro ciliogenesis[J].International Journalof Pharmaceutics,2000,193(2):219-226.
- [31]MATSUYAMA T,MORITA T,HORIKIRI Y,et al.Im-proved nasal absorption of salmon calcitonin by pow-dery formulation with N-acetyl-L-cysteine as a mucolyt-ic agent[J].Journal of Controlled Release,2006,115(2):183-188.
- [32]KHAFAGY E S,MORISHITA M,KAMEI N,et al.Effi-ciency of cell-penetrating peptides on the nasal and in-testinal absorption of therapeutic peptides and proteins[J].International Journal of Pharmaceutics,2009,381(1):49-55.
- [33]KHAFAGY E S,MORISHITA M,ISOWA K,et al.Effect of cell-penetrating peptides on the nasal absorp-tion of insulin[J].Journal of Controlled Release,2009,133(2):103-108.
- [34]WANG Jian,TABATA Y,MORIMOTO K.Aminated ge-latin microspheres as a nasal delivery system for peptidedrugs:Evaluation of in vitro release and in vivo insulinabsorption in rats[J].Journal of Controlled Release,2006,113(1):31-37.
- [35]SEKI T,KANBAYASHI H,NAGAO T,et al.Effect ofaminated gelatin on the nasal absorption of insulin inrats[J].Biological&Pharmaceutical Bulletin,2005,28(3):510-514.
- [36]SEKI T,KANBAYASHI H,CHONOA S,et al.Effectsof a sperminated gelatin on the nasal absorption of in-sulin[J].International Journal of Pharmaceutics,2007,338(1-2):213-218.