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Current Pharmaceutical Biotechnology

Editor-in-Chief

ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

Review Article

Recent Advances in Inhaled Formulations and Pulmonary Insulin Delivery Systems

Author(s): Haofan Liu, Xiaosong Shan, Jiaojiao Yu, Xin Li and Liandong Hu*

Volume 21, Issue 3, 2020

Page: [180 - 193] Pages: 14

DOI: 10.2174/1389201020666191011152248

Price: $65

Abstract

Insulin (INS) therapy played a great role in patients with type 1 and type 2 diabetes to regulate blood glucose levels. Although hypodermic injection was commonly used for insulin delivery, it had some disadvantages such as pain, needle phobia and the risk of infection. Therefore, pulmonary insulin delivery had been developed as an alternative method to overcome the therapeutic challenges in recent years since pulmonary insulin administration showed great improvements in rapid action and circumvention of first-pass hepatic metabolism. This review described the most recent developments in pulmonary insulin administration. Firstly, the structure and physiology of the lung cavity were introduced. Next, the advantages and disadvantages of pulmonary administration were discussed. Then some new dosage forms for pulmonary insulin were investigated including carriers based on surfactants and carriers based on polymers. Finally, innovate insulin inhalers and formulations were also described.

Keywords: Insulin, pulmonary administration, deposition mechanisms, insulin delivery systems, absorption enhancers, insulin inhalers.

Graphical Abstract

[1]
Zhang, Y.; Yu, J.; Kahkoska, A.R.; Wang, J.; Buse, J.B.; Gu, Z. Advances in transdermal insulin delivery. Adv. Drug Deliv. Rev., 2019, 139, 51-70.
[http://dx.doi.org/10.1016/j.addr.2018.12.006] [PMID: 30528729]
[2]
Tauschmann, M.; Hovorka, R. Insulin pump therapy in youth with type 1 diabetes: Toward closed-loop systems. Expert Opin. Drug Deliv., 2014, 11(6), 943-955.
[http://dx.doi.org/10.1517/17425247.2014.910192] [PMID: 24749563]
[3]
Zaykov, A.N.; Mayer, J.P.; DiMarchi, R.D. Pursuit of a perfect insulin. Nat. Rev. Drug Discov., 2016, 15(6), 425-439.
[http://dx.doi.org/10.1038/nrd.2015.36] [PMID: 26988411]
[4]
Shaw, J.E.; Sicree, R.A.; Zimmet, P.Z. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res. Clin. Pract., 2010, 87(1), 4-14.
[http://dx.doi.org/10.1016/j.diabres.2009.10.007] [PMID: 19896746]
[5]
Mo, R.; Jiang, T.; Di, J.; Tai, W.; Gu, Z. Emerging micro- and nanotechnology based synthetic approaches for insulin delivery. Chem. Soc. Rev., 2014, 43(10), 3595-3629.
[http://dx.doi.org/10.1039/c3cs60436e] [PMID: 24626293]
[6]
Morris, A.D.; Boyle, D.I.; McMahon, A.D.; Greene, S.A.; MacDonald, T.M.; Newton, R.W. Adherence to insulin treatment, glycaemic control, and ketoacidosis in insulin-dependent diabetes mellitus. The DARTS/MEMO Collaboration. Diabetes Audit and Research in Tayside Scotland. Medicines Monitoring Unit. Lancet, 1997, 350(9090), 1505-1510.
[http://dx.doi.org/10.1016/S0140-6736(97)06234-X] [PMID: 9388398]
[7]
Al-Tabakha, M.M.; Arida, A.I. Recent challenges in insulin delivery systems: A review. Indian J. Pharm. Sci., 2008, 70(3), 278-286.
[http://dx.doi.org/10.4103/0250-474X.42968] [PMID: 20046733]
[8]
Chu, M.K.; Chen, J.; Gordijo, C.R.; Chiang, S.; Ivovic, A.; Koulajian, K.; Giacca, A.; Wu, X.Y.; Sun, Y. In vitro and in vivo testing of glucose-responsive insulin-delivery microdevices in diabetic rats. Lab Chip, 2012, 12(14), 2533-2539.
[http://dx.doi.org/10.1039/c2lc40139h] [PMID: 22565220]
[9]
Cohen, O.; Vigersky, R.A.; Lee, S.W.; Cordero, T.L.; Kaufman, F.R. Automated insulin delivery system nomenclature. Diabetes Technol. Ther., 2017, 19(6), 379-380.
[http://dx.doi.org/10.1089/dia.2017.0073] [PMID: 28613946]
[10]
Czuba, E.; Diop, M.; Mura, C.; Schaschkow, A.; Langlois, A.; Bietiger, W.; Neidl, R.; Virciglio, A.; Auberval, N.; Julien-David, D.; Maillard, E.; Frere, Y.; Marchioni, E.; Pinget, M.; Sigrist, S. Oral insulin delivery, the challenge to increase insulin bioavailability: Influence of surface charge in nanoparticle system. Int. J. Pharm., 2018, 542(1-2), 47-55.
[http://dx.doi.org/10.1016/j.ijpharm.2018.02.045] [PMID: 29501738]
[11]
West, J.; Niswender, K.D.; Johnson, J.A.; Pugh, M.E.; Gleaves, L.; Fessel, J.P.; Hemnes, A.R. A potential role for insulin resistance in experimental pulmonary hypertension. Eur. Respir. J., 2013, 41(4), 861-871.
[http://dx.doi.org/10.1183/09031936.00030312] [PMID: 22936709]
[12]
Zhou, Q.T.; Leung, S.S.; Tang, P.; Parumasivam, T.; Loh, Z.H.; Chan, H.K. Inhaled formulations and pulmonary drug delivery systems for respiratory infections. Adv. Drug Deliv. Rev., 2015, 85, 83-99.
[http://dx.doi.org/10.1016/j.addr.2014.10.022] [PMID: 25451137]
[13]
Liang, Z.; Ni, R.; Zhou, J.; Mao, S. Recent advances in controlled pulmonary drug delivery. Drug Discov. Today, 2015, 20(3), 380-389.
[http://dx.doi.org/10.1016/j.drudis.2014.09.020] [PMID: 25281854]
[14]
Nahar, K.; Gupta, N.; Gauvin, R.; Absar, S.; Patel, B.; Gupta, V.; Khademhosseini, A.; Ahsan, F. In vitro, in vivo and ex vivo models for studying particle deposition and drug absorption of inhaled pharmaceuticals. Eur. J. Pharm. Sci., 2013, 49(5), 805-818.
[http://dx.doi.org/10.1016/j.ejps.2013.06.004] [PMID: 23797056]
[15]
Ferron, G.A. Aerosol properties and lung deposition. Eur. Respir. J., 1994, 7(8), 1392-1394.
[http://dx.doi.org/10.1183/09031936.94.07081392] [PMID: 7957823]
[16]
O’Callaghan, C.; Barry, P.W. The science of nebulised drug delivery. Thorax, 1997, 52(Suppl. 2), S31-S44.
[http://dx.doi.org/10.1136/thx.52.2008.S31] [PMID: 9155849]
[17]
Yoo, N.Y.; Youn, Y.S.; Oh, N.M.; Oh, K.T.; Lee, D.K.; Cha, K.H.; Oh, Y.T.; Lee, E.S. Antioxidant encapsulated porous poly(lactide-co-glycolide) microparticles for developing long acting inhalation system. Colloids Surf. B Biointerfaces, 2011, 88(1), 419-424.
[http://dx.doi.org/10.1016/j.colsurfb.2011.07.024] [PMID: 21820282]
[18]
Strong, P.; Ito, K.; Murray, J.; Rapeport, G. Current approaches to the discovery of novel inhaled medicines. Drug Discov. Today, 2018, 23(10), 1705-1717.
[http://dx.doi.org/10.1016/j.drudis.2018.05.017] [PMID: 29775668]
[19]
Kirch, J.; Guenther, M.; Doshi, N.; Schaefer, U.F.; Schneider, M.; Mitragotri, S.; Lehr, C.M. Mucociliary clearance of micro- and nanoparticles is independent of size, shape and charge--an ex vivo and in silico approach. J. Control. Release, 2012, 159(1), 128-134.
[http://dx.doi.org/10.1016/j.jconrel.2011.12.015] [PMID: 22226774]
[20]
Rajabnezhad, S.; Casettari, L.; Lam, J.K.W.; Nomani, A.; Torkamani, M.R.; Palmieri, G.F.; Rajabnejad, M.R.; Darbandi, M.A. Pulmonary delivery of rifampicin microspheres using lower generation polyamidoamine dendrimers as a carrier. Powder Technol., 2016, 291, 366-374.
[http://dx.doi.org/10.1016/j.powtec.2015.12.037]
[21]
Sayani, A.P.; Chien, Y.W. Systemic delivery of peptides and proteins across absorptive mucosae. Crit. Rev. Ther. Drug Carrier Syst., 1996, 13(1-2), 85-184.
[PMID: 8853960]
[22]
Liu, F.Y.; Shao, Z.; Kildsig, D.O.; Mitra, A.K. Pulmonary delivery of free and liposomal insulin. Pharm. Res., 1993, 10(2), 228-232.
[http://dx.doi.org/10.1023/A:1018934810512] [PMID: 8456069]
[23]
Rouse, J.J.; Whateley, T.L.; Thomas, M.; Eccleston, G.M. Controlled drug delivery to the lung: Influence of hyaluronic acid solution conformation on its adsorption to hydrophobic drug particles. Int. J. Pharm., 2007, 330(1-2), 175-182.
[http://dx.doi.org/10.1016/j.ijpharm.2006.11.066] [PMID: 17207592]
[24]
Byron, P.R.; Hindle, M.; Lange, C.F.; Longest, P.W.; McRobbie, D.; Oldham, M.J.; Olsson, B.; Thiel, C.G.; Wachtel, H.; Finlay, W.H. In vivo-in vitro correlations: predicting pulmonary drug deposition from pharmaceutical aerosols. J. Aerosol Med. Pulm. Drug Deliv., 2010, 23(Suppl. 2), S59-S69.
[http://dx.doi.org/10.1089/jamp.2010.0846] [PMID: 21133801]
[25]
Huang, Y.Y.; Wang, C.H. Pulmonary delivery of insulin by liposomal carriers. J. Control. Release, 2006, 113(1), 9-14.
[http://dx.doi.org/10.1016/j.jconrel.2006.03.014] [PMID: 16730838]
[26]
Dhanani, J.; Fraser, J.F.; Chan, H.K.; Rello, J.; Cohen, J.; Roberts, J.A. Fundamentals of aerosol therapy in critical care. Crit. Care, 2016, 20(1), 269.
[http://dx.doi.org/10.1186/s13054-016-1448-5] [PMID: 27716346]
[27]
Dolovich, M.B.; Dhand, R. Aerosol drug delivery: Developments in device design and clinical use. Lancet, 2011, 377(9770), 1032-1045.
[http://dx.doi.org/10.1016/S0140-6736(10)60926-9] [PMID: 21036392]
[28]
Rangaraj, N.; Pailla, S.R.; Sampathi, S. Insight into pulmonary drug delivery: Mechanism of drug deposition to device characterization and regulatory requirements. Pulm. Pharmacol. Ther., 2019, 54, 1-21.
[http://dx.doi.org/10.1016/j.pupt.2018.11.004] [PMID: 30447295]
[29]
Germershaus, O.; Schultz, I.; Lühmann, T.; Beck-Broichsitter, M.; Högger, P.; Meinel, L. Insulin-like growth factor-I aerosol formulations for pulmonary delivery. Eur. J. Pharm. Biopharm., 2013, 85(1), 61-68.
[http://dx.doi.org/10.1016/j.ejpb.2013.03.011] [PMID: 23958318]
[30]
Klingler, C.; Müller, B.W.; Steckel, H. Insulin-micro- and nanoparticles for pulmonary delivery. Int. J. Pharm., 2009, 377(1-2), 173-179.
[http://dx.doi.org/10.1016/j.ijpharm.2009.05.008] [PMID: 19446621]
[31]
Xu, Y.Y.; Lu, C.T.; Fu, H.X.; Zhao, Y.Z.; Yang, W.; Li, X.; Zhang, L.; Li, X.K.; Zhang, M. Comparing the enhancement efficiency between liposomes and microbubbles for insulin pulmonary absorption. Diabetes Technol. Ther., 2011, 13(7), 759-765.
[http://dx.doi.org/10.1089/dia.2010.0231] [PMID: 21510752]
[32]
Wang, X.; Liu, D.; Wang, M.; Chen, Z.; Yin, T.; Shen, W. Liquid-liquid phase equilibrium and the effect of a water-soluble polymer on the interaction between droplets in water-in-oil microemulsions. Soft Matter, 2018, 14(48), 9950-9958.
[http://dx.doi.org/10.1039/C8SM01562G] [PMID: 30488934]
[33]
Mojeiko, G.; de Brito, M.; Salata, G.C.; Lopes, L.B. Combination of microneedles and microemulsions to increase celecoxib topical delivery for potential application in chemoprevention of breast cancer. Int. J. Pharm., 2019, 560, 365-376.
[http://dx.doi.org/10.1016/j.ijpharm.2019.02.011] [PMID: 30772460]
[34]
Constantinides, P.P. Lipid microemulsions for improving drug dissolution and oral absorption: Physical and biopharmaceutical aspects. Pharm. Res., 1995, 12(11), 1561-1572.
[http://dx.doi.org/10.1023/A:1016268311867] [PMID: 8592652]
[35]
Lawrence, M.J.; Rees, G.D. Microemulsion-based media as novel drug delivery systems. Adv. Drug Deliv. Rev., 2000, 45(1), 89-121.
[http://dx.doi.org/10.1016/S0169-409X(00)00103-4] [PMID: 11104900]
[36]
Patil, N.H.; Devarajan, P.V. Enhanced insulin absorption from sublingual microemulsions: effect of permeation enhancers. Drug Deliv. Transl. Res., 2014, 4(5-6), 429-438.
[http://dx.doi.org/10.1007/s13346-014-0205-z] [PMID: 25787205]
[37]
Malakar, J.; Sen, S.O.; Nayak, A.K.; Sen, K.K. Development and evaluation of microemulsions for transdermal delivery of insulin. ISRN Pharm., 2011, 2011780150
[http://dx.doi.org/10.5402/2011/780150] [PMID: 22389858]
[38]
Li, H.Y.; Xu, E.Y. Innovative pMDI formulations of spray-dried nanoparticles for efficient pulmonary drug delivery. Int. J. Pharm., 2017, 530(1-2), 12-20.
[http://dx.doi.org/10.1016/j.ijpharm.2017.07.040] [PMID: 28723410]
[39]
Fonte, P.; Andrade, F.; Araújo, F.; Andrade, C.; Neves, Jd.; Sarmento, B. Chitosan-coated solid lipid nanoparticles for insulin delivery. Methods Enzymol., 2012, 508, 295-314.
[http://dx.doi.org/10.1016/B978-0-12-391860-4.00015-X] [PMID: 22449932]
[40]
Sarmento, B.; Martins, S.; Ferreira, D.; Souto, E.B. Oral insulin delivery by means of solid lipid nanoparticles. Int. J. Nanomedicine, 2007, 2(4), 743-749.
[PMID: 18203440]
[41]
Liu, J.; Gong, T.; Fu, H.; Wang, C.; Wang, X.; Chen, Q.; Zhang, Q.; He, Q.; Zhang, Z. Solid lipid nanoparticles for pulmonary delivery of insulin. Int. J. Pharm., 2008, 356(1-2), 333-344.
[http://dx.doi.org/10.1016/j.ijpharm.2008.01.008] [PMID: 18281169]
[42]
Yang, X.; Liu, Y.; Liu, C.; Zhang, N. Biodegradable solid lipid nanoparticle flocculates for pulmonary delivery of insulin. J. Biomed. Nanotechnol., 2012, 8(5), 834-842.
[http://dx.doi.org/10.1166/jbn.2012.1429] [PMID: 22888755]
[43]
Wu, W.; Lu, Y.; Qi, J. Oral delivery of liposomes. Ther. Deliv., 2015, 6(11), 1239-1241.
[http://dx.doi.org/10.4155/tde.15.69] [PMID: 26584253]
[44]
Zhang, L.J.; Kuang, Y.; Zhuo, R.X.; Liu, Z.L.; Huang, S.W. Anionic long circulating liposomes for hepatic targeted delivery of cisplatin. J. Control. Release, 2015, 213e72
[http://dx.doi.org/10.1016/j.jconrel.2015.05.119] [PMID: 27005219]
[45]
Chono, S.; Fukuchi, R.; Seki, T.; Morimoto, K. Aerosolized liposomes with dipalmitoyl phosphatidylcholine enhance pulmonary insulin delivery. J. Control. Release, 2009, 137(2), 104-109.
[http://dx.doi.org/10.1016/j.jconrel.2009.03.019] [PMID: 19351549]
[46]
Depreter, F.; Burniat, A.; Blocklet, D.; Lacroix, S.; Cnop, M.; Fery, F.; Aelst, N.V.; Pilcer, G.; Deleers, M.; Goldman, S.; Amighi, K. Comparative pharmacoscintigraphic and pharmacokinetic evaluation of two new formulations of inhaled insulin in type 1 diabetic patients. Eur. J. Pharm. Biopharm., 2012, 80(1), 4-13.
[http://dx.doi.org/10.1016/j.ejpb.2011.09.015] [PMID: 21983605]
[47]
Shi, K.; Liu, Y.; Ke, L.; Fang, Y.; Yang, R.; Cui, F. Epsilon-poly-L-lysine guided improving pulmonary delivery of supramolecular self-assembled insulin nanospheres. Int. J. Biol. Macromol., 2015, 72, 1441-1450.
[http://dx.doi.org/10.1016/j.ijbiomac.2014.10.023] [PMID: 25450837]
[48]
Andrade, F.; Videira, M.; Ferreira, D.; Sarmento, B. Nanocarriers for pulmonary administration of peptides and therapeutic proteins. Nanomedicine (Lond.), 2011, 6(1), 123-141.
[http://dx.doi.org/10.2217/nnm.10.143] [PMID: 21182424]
[49]
Lim, Y.H.; Tiemann, K.M.; Hunstad, D.A.; Elsabahy, M.; Wooley, K.L. Polymeric nanoparticles in development for treatment of pulmonary infectious diseases. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol., 2016, 8(6), 842-871.
[http://dx.doi.org/10.1002/wnan.1401] [PMID: 27016134]
[50]
Huang, X.; Du, Y.Z.; Yuan, H.; Hu, F.Q. Preparation and pharmacodynamics of low-molecular-weight chitosan nanoparticles containing insulin. Carbohydr. Polym., 2009, 76(3), 368-373.
[http://dx.doi.org/10.1016/j.carbpol.2008.10.025]
[51]
Win, K.Y.; Ye, E.; Teng, C.P.; Jiang, S.; Han, M.Y. Engineering polymeric microparticles as theranostic carriers for selective delivery and cancer therapy. Adv. Healthc. Mater., 2013, 2(12), 1571-1575.
[http://dx.doi.org/10.1002/adhm.201300077] [PMID: 23712912]
[52]
Lu, D.; Garcia-Contreras, L.; Muttil, P.; Padilla, D.; Xu, D.; Liu, J.; Braunstein, M.; McMurray, D.N.; Hickey, A.J. Pulmonary immunization using antigen 85-B polymeric microparticles to boost tuberculosis immunity. AAPS J., 2010, 12(3), 338-347.
[http://dx.doi.org/10.1208/s12248-010-9193-1] [PMID: 20422340]
[53]
Grenha, A.; Remuñán-López, C.; Carvalho, E.L.; Seijo, B. Microspheres containing lipid/chitosan nanoparticles complexes for pulmonary delivery of therapeutic proteins. Eur. J. Pharm. Biopharm., 2008, 69(1), 83-93.
[http://dx.doi.org/10.1016/j.ejpb.2007.10.017] [PMID: 18166446]
[54]
Garcia-Contreras, L.; Morçöl, T.; Bell, S.J.D.; Hickey, A.J. Evaluation of novel particles as pulmonary delivery systems for insulin in rats. AAPS PharmSci, 2003, 5(2)E9
[http://dx.doi.org/10.1208/ps050209] [PMID: 12866936]
[55]
Hamishehkar, H.; Emami, J.; Najafabadi, A.R.; Gilani, K.; Minaiyan, M.; Hassanzadeh, K.; Mahdavi, H.; Koohsoltani, M.; Nokhodchi, A. Pharmacokinetics and pharmacodynamics of controlled release insulin loaded PLGA microcapsules using dry powder inhaler in diabetic rats. Biopharm. Drug Dispos., 2010, 31(2-3), 189-201.
[http://dx.doi.org/10.1002/bdd.702] [PMID: 20238376]
[56]
Ungaro, F.; d’Emmanuele di Villa Bianca, R.; Giovino, C.; Miro, A.; Sorrentino, R.; Quaglia, F.; La Rotonda, M.I. Insulin-loaded PLGA/cyclodextrin large porous particles with improved aerosolization properties: In vivo deposition and hypoglycaemic activity after delivery to rat lungs. J. Control. Release, 2009, 135(1), 25-34.
[http://dx.doi.org/10.1016/j.jconrel.2008.12.011] [PMID: 19154761]
[57]
Lee, J.; Oh, Y.J.; Lee, S.K.; Lee, K.Y. Facile control of porous structures of polymer microspheres using an osmotic agent for pulmonary delivery. J. Control. Release, 2010, 146(1), 61-67.
[http://dx.doi.org/10.1016/j.jconrel.2010.05.026] [PMID: 20553775]
[58]
Du, A.W.; Stenzel, M.H. Drug carriers for the delivery of therapeutic peptides. Biomacromolecules, 2014, 15(4), 1097-1114.
[http://dx.doi.org/10.1021/bm500169p] [PMID: 24661025]
[59]
Teijeiro-Osorio, D.; Remuñán-López, C.; Alonso, M.J. New generation of hybrid poly/oligosaccharide nanoparticles as carriers for the nasal delivery of macromolecules. Biomacromolecules, 2009, 10(2), 243-249.
[http://dx.doi.org/10.1021/bm800975j] [PMID: 19117404]
[60]
He, L.; Gao, Y.; Lin, Y.; Katsumi, H.; Fujita, T.; Yamamoto, A. Improvement of pulmonary absorption of insulin and other water-soluble compounds by polyamines in rats. J. Control. Release, 2007, 122(1), 94-101.
[http://dx.doi.org/10.1016/j.jconrel.2007.06.017] [PMID: 17651854]
[61]
Dong, Z.; Hamid, K.A.; Gao, Y.; Lin, Y.; Katsumi, H.; Sakane, T.; Yamamoto, A. Polyamidoamine dendrimers can improve the pulmonary absorption of insulin and calcitonin in rats. J. Pharm. Sci., 2011, 100(5), 1866-1878.
[http://dx.doi.org/10.1002/jps.22428] [PMID: 21374620]
[62]
Brashier, D.B.; Khadka, A.; Anantharamu, T.; Sharma, A.K.; Gupta, A.K.; Sharma, S.; Dahiya, N. Inhaled insulin: A “puff” than a “shot” before meals. J. Pharmacol. Pharmacother., 2015, 6(3), 126-129.
[http://dx.doi.org/10.4103/0976-500X.162013] [PMID: 26311994]
[63]
Davis, S.N. The role of inhaled insulin in the treatment of type 2 diabetes. J. Diabetes Complications, 2008, 22(6), 420-429.
[http://dx.doi.org/10.1016/j.jdiacomp.2007.05.001] [PMID: 18413196]
[64]
Rashid, J.; Absar, S.; Nahar, K.; Gupta, N.; Ahsan, F. Newer devices and improved formulations of inhaled insulin. Expert Opin. Drug Deliv., 2015, 12(6), 917-928.
[http://dx.doi.org/10.1517/17425247.2015.990436] [PMID: 25485886]
[65]
Ledet, G.; Graves, R.A.; Bostanian, L.A.; Mandal, T.K. A second-generation inhaled insulin for diabetes mellitus. Am. J. Health Syst. Pharm., 2015, 72(14), 1181-1187.
[http://dx.doi.org/10.2146/ajhp140540] [PMID: 26150567]
[66]
Jeffry, G.W.; Danforth, P.M.; Thomas, E.T. Spray-dried PulmoSphere™ formulations for inhalation comprising crystalline drug particles. AAPS PharmSci, 2019, 20, 103.
[http://dx.doi.org/10.1208/s12249-018-1280-0]
[67]
Santos Cavaiola, T.; Edelman, S. Inhaled insulin: A breath of fresh air? A review of inhaled insulin. Clin. Ther., 2014, 36(8), 1275-1289.
[http://dx.doi.org/10.1016/j.clinthera.2014.06.025] [PMID: 25044021]
[68]
Kugler, A.J.; Fabbio, K.L.; Pham, D.Q.; Nadeau, D.A. Inhaled technosphere insulin: A novel delivery system and formulation for the treatment of types 1 and 2 diabetes mellitus. Pharmacotherapy, 2015, 35(3), 298-314.
[http://dx.doi.org/10.1002/phar.1555] [PMID: 25809179]
[69]
Klonoff, D.C. Afrezza inhaled insulin: The fastest-acting FDA-approved insulin on the market has favorable properties. J. Diabetes Sci. Technol., 2014, 8(6), 1071-1073.
[http://dx.doi.org/10.1177/1932296814555820] [PMID: 25355710]
[70]
Heinemann, L.; Parkin, C.G. Rethinking the viability and utility of inhaled insulin in clinical practice. J. Diabetes Res., 2018, 20184568903
[http://dx.doi.org/10.1155/2018/4568903] [PMID: 29707584]

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