Generic placeholder image

Current Drug Delivery

Editor-in-Chief

ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Review Article

Emerging Strategies to Improve the Stability and Bioavailability of Insulin: An Update on Formulations and Delivery Approaches

Author(s): Pak Kheong Tan, Umah Rani Kuppusamy, Kek Heng Chua and Bavani Arumugam*

Volume 20, Issue 8, 2023

Published on: 16 December, 2022

Page: [1141 - 1162] Pages: 22

DOI: 10.2174/1567201820666221102094433

Price: $65

conference banner
Abstract

One of the primary goals of diabetes management is to maintain blood glucose levels within a normal range, and insulin plays a vital role in achieving this. All Type 1 DM patients and advanced Type 2 DM patients require insulin. Insulin is administered subcutaneously, which may cause patient discomfort from the use of needles. Therefore, developing alternative routes of insulin administration has always been a major focus of diabetes research. This review aims to provide an update on the insulin formulations and delivery routes as well as strategies used to improve its stability and bioavailability for the treatment of diabetes.

Graphical Abstract

[1]
Kurtzhals, P.; Nishimura, E.; Haahr, H.; Høeg-Jensen, T.; Johansson, E.; Madsen, P.; Sturis, J.; Kjeldsen, T. Commemorating insulin’s centennial: Engineering insulin pharmacology towards physiology. Trends Pharmacol. Sci., 2021, 42(8), 620-639.
[http://dx.doi.org/10.1016/j.tips.2021.05.005] [PMID: 34148677]
[2]
Leto, D.; Saltiel, A.R. Regulation of glucose transport by insulin: Traffic control of GLUT4. Nat. Rev. Mol. Cell Biol., 2012, 13(6), 383-396.
[http://dx.doi.org/10.1038/nrm3351] [PMID: 22617471]
[3]
International Diabetes Federation.IDF Diabetes Atlas; 10th ed; Brussels, Belgium,, 2021. Available from: https://www.diabetesatlas.org
[4]
Classification and diagnosis of diabetes: Standards of Medical Care in Diabetes—2021. Diabetes Care, 2021, 44(Suppl. 1), S15-S33.
[http://dx.doi.org/10.2337/dc21-S002] [PMID: 33298413]
[5]
Ismail, R.; Csóka, I. Novel strategies in the oral delivery of antidiabetic peptide drugs – Insulin, GLP 1 and its analogs. Eur. J. Pharm. Biopharm., 2017, 115, 257-267.
[http://dx.doi.org/10.1016/j.ejpb.2017.03.015] [PMID: 28336368]
[6]
Dunn, M.F. Zinc-ligand interactions modulate assembly and stability of the insulin hexamer - a review. Biometals, 2005, 18(4), 295-303.
[http://dx.doi.org/10.1007/s10534-005-3685-y] [PMID: 16158220]
[7]
Huus, K.; Havelund, S.; Olsen, H.B.; van de Weert, M.; Frokjaer, S. Thermal dissociation and unfolding of insulin. Biochemistry, 2005, 44(33), 11171-11177.
[http://dx.doi.org/10.1021/bi0507940] [PMID: 16101301]
[8]
Østergaard, M.; Mishra, N.K.; Jensen, K.J. The ABC of insulin: The organic chemistry of a small protein. Chemistry, 2020, 26(38), 8341-8357.
[http://dx.doi.org/10.1002/chem.202000337] [PMID: 32196765]
[9]
Richter, B.; Bongaerts, B.; Metzendorf, M.I. Thermal stability and storage of human insulin. Cochrane Database Syst. Rev., 2022, (1), 1-10.
[10]
Kabotso, D.E.K.; Smiley, D.; Mayer, J.P.; Gelfanov, V.M.; Perez-Tilve, D.; DiMarchi, R.D.; Pohl, N.L.B.; Liu, F. Addition of sialic acid to insulin confers superior physical properties and bioequivalence. J. Med. Chem., 2020, 63(11), 6134-6143.
[http://dx.doi.org/10.1021/acs.jmedchem.0c00266] [PMID: 32406685]
[11]
Meis, C.M.; Salzman, E.E.; Maikawa, C.L.; Smith, A.A.A.; Mann, J.L.; Grosskopf, A.K.; Appel, E.A. Self-assembled, dilution-responsive hydrogels for enhanced thermal stability of insulin biopharmaceuticals. ACS Biomater. Sci. Eng., 2021, 7(9), 4221-4229.
[http://dx.doi.org/10.1021/acsbiomaterials.0c01306] [PMID: 34510910]
[12]
Ji, L.; Chen, L.; Wang, Y.; Ma, Z.; Ran, X.; Sun, Z.; Xu, X.; Wang, G.; Guo, L.; Shan, Z. Study protocol for a prospective, multicenter, randomized, open-label, parallel-group clinical trial comparing the efficacy and safety of a needle-free insulin injector and a conventional insulin pen in controlling blood glucose concentrations in Chinese patients with type 2 diabetes mellitus (the FREE Study). Adv. Ther., 2019, 36(6), 1485-1496.
[http://dx.doi.org/10.1007/s12325-019-00951-4] [PMID: 31004325]
[13]
Najjar, S.M.; Perdomo, G. Hepatic insulin clearance: Mechanism and physiology. Physiology , 2019, 34(3), 198-215.
[http://dx.doi.org/10.1152/physiol.00048.2018] [PMID: 30968756]
[14]
Gradel, A.K.J.; Porsgaard, T.; Lykkesfeldt, J.; Seested, T.; Gram-Nielsen, S.; Kristensen, N.R.; Refsgaard, H.H.F. Factors affecting the absorption of subcutaneously administered insulin: Effect on variability. J. Diabetes Res., 2018, 2018, 1-17.
[http://dx.doi.org/10.1155/2018/1205121] [PMID: 30116732]
[15]
Thewjitcharoen, Y.; Prasartkaew, H.; Tongsumrit, P.; Wongjom, S.; Boonchoo, C.; Butadej, S.; Nakasatien, S.; Karndumri, K.; Veerasom-boonsin, V.; Krittiyawong, S.; Himathongkam, T. Prevalence, risk factors, and clinical characteristics of lipodystrophy in insulin-treated patients with diabetes: An old problem in a new era of modern insulin. Diabetes Metab. Syndr. Obes., 2020, 13, 4609-4620.
[http://dx.doi.org/10.2147/DMSO.S282926] [PMID: 33273836]
[16]
Goldberg, M.; Gomez-Orellana, I. Challenges for the oral delivery of macromolecules. Nat. Rev. Drug Discov., 2003, 2(4), 289-295.
[http://dx.doi.org/10.1038/nrd1067] [PMID: 12669028]
[17]
Hua, S. Advances in oral drug delivery for regional targeting in the gastrointestinal tract-influence of physiological, pathophysiological and pharmaceutical factors. Front. Pharmacol., 2020, 11(524), 524.
[http://dx.doi.org/10.3389/fphar.2020.00524] [PMID: 32425781]
[18]
Fonte, P.; Araújo, F.; Silva, C.; Pereira, C.; Reis, S.; Santos, H.A.; Sarmento, B. Polymer-based nanoparticles for oral insulin delivery: Revisited approaches. Biotechnol. Adv., 2015, 33(6), 1342-1354.
[http://dx.doi.org/10.1016/j.biotechadv.2015.02.010] [PMID: 25728065]
[19]
Hejazi, R.; Amiji, M. Chitosan-based gastrointestinal delivery systems. J. Control. Release, 2003, 89(2), 151-165.
[http://dx.doi.org/10.1016/S0168-3659(03)00126-3] [PMID: 12711440]
[20]
Zhang, Y.; Wei, W.; Lv, P.; Wang, L.; Ma, G. Preparation and evaluation of alginate–chitosan microspheres for oral delivery of insulin. Eur. J. Pharm. Biopharm., 2011, 77(1), 11-19.
[http://dx.doi.org/10.1016/j.ejpb.2010.09.016] [PMID: 20933083]
[21]
Li, S.; Qin, T.; Chen, T.; Wang, J.; Zeng, Q. Poly(vinyl alcohol)/poly(hydroxypropyl methacrylate-co-methacrylic acid) as pH-sensitive semi-IPN hydrogels for oral insulin delivery: preparation and characterization. Iran. Polym. J., 2021, 30(4), 343-353.
[http://dx.doi.org/10.1007/s13726-020-00893-7]
[22]
Lin, P.Y.; Chuang, E.Y.; Chiu, Y.H.; Chen, H.L.; Lin, K.J.; Juang, J.H.; Chiang, C.H.; Mi, F.L.; Sung, H.W. Safety and efficacy of self-assembling bubble carriers stabilized with sodium dodecyl sulfate for oral delivery of therapeutic proteins. J. Control. Release, 2017, 259, 168-175.
[http://dx.doi.org/10.1016/j.jconrel.2016.12.018] [PMID: 28007514]
[23]
Banerjee, A.; Ibsen, K.; Brown, T.; Chen, R.; Agatemor, C.; Mitragotri, S. Ionic liquids for oral insulin delivery. Proc. Natl. Acad. Sci. USA, 2018, 115(28), 7296-7301.
[http://dx.doi.org/10.1073/pnas.1722338115] [PMID: 29941553]
[24]
Kammona, O.; Kiparissides, C. Recent advances in nanocarrier-based mucosal delivery of biomolecules. J. Control. Release, 2012, 161(3), 781-794.
[http://dx.doi.org/10.1016/j.jconrel.2012.05.040] [PMID: 22659331]
[25]
Renukuntla, J.; Vadlapudi, A.D.; Patel, A.; Boddu, S.H.S.; Mitra, A.K. Approaches for enhancing oral bioavailability of peptides and proteins. Int. J. Pharm., 2013, 447(1-2), 75-93.
[http://dx.doi.org/10.1016/j.ijpharm.2013.02.030] [PMID: 23428883]
[26]
Jaafar, M.H.M.; Hamid, K.A. Chitosan-coated alginate nanoparticles enhanced absorption profile of insulin via oral administration. Curr. Drug Deliv., 2019, 16(7), 672-686.
[http://dx.doi.org/10.2174/1567201816666190620110748] [PMID: 31250754]
[27]
Eilleia, S.Y.; Soliman, M.E.; Niedermayer, S.; Schmidt, A.; Mansour, S.; Geneidi, A.S. Examining insulin adsorption onto mesoporous silica microparticles for oral delivery. Curr. Drug Deliv., 2018, 15(4), 541-553.
[http://dx.doi.org/10.2174/1567201814666171002142023] [PMID: 28969564]
[28]
Ensign, L.M.; Cone, R.; Hanes, J. Oral drug delivery with polymeric nanoparticles: The gastrointestinal mucus barriers. Adv. Drug Deliv. Rev., 2012, 64(6), 557-570.
[http://dx.doi.org/10.1016/j.addr.2011.12.009] [PMID: 22212900]
[29]
Sgorla, D.; Lechanteur, A.; Almeida, A.; Sousa, F.; Melo, E.; Bunhak, É.; Mainardes, R.; Khalil, N.; Cavalcanti, O.; Sarmento, B. Development and characterization of lipid-polymeric nanoparticles for oral insulin delivery. Expert Opin. Drug Deliv., 2018, 15(3), 213-222.
[http://dx.doi.org/10.1080/17425247.2018.1420050] [PMID: 29257904]
[30]
Li, Y.; Ji, W.; Peng, H.; Zhao, R.; Zhang, T.; Lu, Z.; Yang, J.; Liu, R.; Zhang, X. Charge-switchable zwitterionic polycarboxybetaine particle as an intestinal permeation enhancer for efficient oral insulin delivery. Theranostics, 2021, 11(9), 4452-4466.
[http://dx.doi.org/10.7150/thno.54176] [PMID: 33754071]
[31]
Benyettou, F.; Kaddour, N.; Prakasam, T.; Das, G.; Sharma, S.K.; Thomas, S.A.; Bekhti-Sari, F.; Whelan, J.; Alkhalifah, M.A.; Khair, M.; Traboulsi, H.; Pasricha, R.; Jagannathan, R.; Mokhtari-Soulimane, N.; Gándara, F.; Trabolsi, A. In vivo oral insulin delivery via covalent organic frameworks. Chem. Sci. (Camb.), 2021, 12(17), 6037-6047.
[http://dx.doi.org/10.1039/D0SC05328G] [PMID: 33995999]
[32]
Li, S.; Liang, N.; Yan, P.; Kawashima, Y.; Sun, S. Inclusion complex based on N-acetyl-L-cysteine and arginine modified hydroxypropyl-β-cyclodextrin for oral insulin delivery. Carbohydr. Polym., 2021, 252, 117202.
[http://dx.doi.org/10.1016/j.carbpol.2020.117202] [PMID: 33183638]
[33]
Mutlu-Agardan, N.B.; Han, S. In vitro and in vivo evaluations on nanoparticle and phospholipid hybrid nanoparticles with absorption enhancers for oral insulin delivery. Pharm. Dev. Technol., 2021, 26(2), 157-166.
[http://dx.doi.org/10.1080/10837450.2020.1849282] [PMID: 33183103]
[34]
Xu, Z.; Chen, L.; Duan, X.; Li, X.; Ren, H. Microparticles based on alginate/chitosan/casein three‐dimensional system for oral insulin delivery. Polym. Adv. Technol., 2021, 32(11), 4352-4361.
[http://dx.doi.org/10.1002/pat.5437]
[35]
Cui, Z.; Qin, L.; Guo, S.; Cheng, H.; Zhang, X.; Guan, J.; Mao, S. Design of biotin decorated enterocyte targeting mucoinert nanocomplexes for enhanced oral insulin delivery. Carbohydr. Polym., 2021, 261, 117873.
[http://dx.doi.org/10.1016/j.carbpol.2021.117873] [PMID: 33766360]
[36]
Martínez-López, A.L.; González-Navarro, C.J.; Aranaz, P.; Vizmanos, J.L.; Irache, J.M. In vivo testing of mucus-permeating nanoparticles for oral insulin delivery using Caenorhabditis elegans as a model under hyperglycemic conditions. Acta Pharm. Sin. B, 2021, 11(4), 989-1002.
[http://dx.doi.org/10.1016/j.apsb.2021.02.020] [PMID: 33996411]
[37]
Cheng, H.; Guo, S.; Cui, Z.; Zhang, X.; Huo, Y.; Guan, J.; Mao, S. Design of folic acid decorated virus-mimicking nanoparticles for enhanced oral insulin delivery. Int. J. Pharm., 2021, 596, 120297.
[http://dx.doi.org/10.1016/j.ijpharm.2021.120297] [PMID: 33508345]
[38]
Rao, R.; Liu, X.; Li, Y.; Tan, X.; Zhou, H.; Bai, X.; Yang, X.; Liu, W. Bioinspired zwitterionic polyphosphoester modified porous silicon nanoparticles for efficient oral insulin delivery. Biomater. Sci., 2021, 9(3), 685-699.
[http://dx.doi.org/10.1039/D0BM01772H] [PMID: 33330897]
[39]
Li, M.; Sun, Y.; Ma, C.; Hua, Y.; Zhang, L.; Shen, J. Design and investigation of penetrating mechanism of octaarginine-modified alginate nanoparticles for improving intestinal insulin delivery. J. Pharm. Sci., 2021, 110(1), 268-279.
[http://dx.doi.org/10.1016/j.xphs.2020.07.004] [PMID: 32663595]
[40]
Anchan, R.B.; Koland, M. Oral insulin delivery by chitosan coated solid lipid nanoparticles: Ex vivo and in vivo studies. J. Young Pharm., 2021, 13(1), 43-48.
[http://dx.doi.org/10.5530/jyp.2021.13.10]
[41]
Morales-Burgos, A.M.; Carvajal-Millan, E.; Sotelo-Cruz, N.; Rascón-Chu, A.; Lizardi-Mendoza, J.; López-Franco, Y.L.; Martínez-Porchas, M.; Canett-Romero, R. Highly cross-linked arabinoxylans microspheres as a microbiota-activated carrier for colon-specific insulin delivery. Eur. J. Pharm. Biopharm., 2021, 163, 16-22.
[http://dx.doi.org/10.1016/j.ejpb.2021.02.014] [PMID: 33774161]
[42]
Zhang, Y.; Xiong, G.M.; Ali, Y.; Boehm, B.O.; Huang, Y.Y.; Venkatraman, S. Layer-by-layer coated nanoliposomes for oral delivery of insulin. Nanoscale, 2021, 13(2), 776-789.
[http://dx.doi.org/10.1039/D0NR06104B] [PMID: 33295926]
[43]
Li, J.; Wu, H.; Jiang, K.; Liu, Y.; Yang, L.; Park, H.J. Alginate calcium microbeads containing chitosan nanoparticles for controlled insulin release. Appl. Biochem. Biotechnol., 2021, 193(2), 463-478.
[http://dx.doi.org/10.1007/s12010-020-03420-9] [PMID: 33026616]
[44]
Song, J.G.; Lee, S.H.; Han, H.K. Development of an M cell targeted nanocomposite system for effective oral protein delivery: preparation, in vitro and in vivo characterization. J. Nanobiotechnology, 2021, 19(1), 15.
[http://dx.doi.org/10.1186/s12951-020-00750-y] [PMID: 33422063]
[45]
Kaur, I.; Nallamothu, B.; Kuche, K.; Katiyar, S.S.; Chaudhari, D.; Jain, S. Exploring protein stabilized multiple emulsion with permeation enhancer for oral delivery of insulin. Int. J. Biol. Macromol., 2021, 167, 491-501.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.11.190] [PMID: 33279562]
[46]
Gao, Y.; He, Y.; Zhang, H.; Zhang, Y.; Gao, T.; Wang, J.H.; Wang, S. Zwitterion-functionalized mesoporous silica nanoparticles for enhancing oral delivery of protein drugs by overcoming multiple gastrointestinal barriers. J. Colloid Interface Sci., 2021, 582(Pt A), 364-375.
[http://dx.doi.org/10.1016/j.jcis.2020.08.010] [PMID: 32861041]
[47]
Song, M.; Wang, H.; Chen, K. Oral insulin delivery by carboxymethyl-β-cyclodextrin-grafted chitosan nanoparticles for improving diabetic treatment. Artif. Cells Nanomed. Biotechnol., 2018, 46(s3), 774-782.
[http://dx.doi.org/10.1080/21691401.2018.1511575]
[48]
Kim, J.U.; Shahbaz, H.M.; Lee, H.; Kim, T.; Yang, K.; Roh, Y.H.; Park, J. Optimization of phytic acid-crosslinked chitosan microspheres for oral insulin delivery using response surface methodology. Int. J. Pharm., 2020, 588, 119736.
[http://dx.doi.org/10.1016/j.ijpharm.2020.119736] [PMID: 32758596]
[49]
Iyer, H.; Khedkar, A.; Verma, M. Oral insulin - a review of current status. Diabetes Obes. Metab., 2010, 12(3), 179-185.
[http://dx.doi.org/10.1111/j.1463-1326.2009.01150.x] [PMID: 20151994]
[50]
Heinemann, L.; Jacques, Y. Oral insulin and buccal insulin: A critical reappraisal. J. Diabetes Sci. Technol., 2009, 3(3), 568-584.
[http://dx.doi.org/10.1177/193229680900300323] [PMID: 20144297]
[51]
Khedkar, A.; Iyer, H.; Anand, A.; Verma, M.; Krishnamurthy, S.; Savale, S.; Atignal, A. A dose range finding study of novel oral insulin (IN-105) under fed conditions in type 2 diabetes mellitus subjects. Diabetes Obes. Metab., 2010, 12(8), 659-664.
[http://dx.doi.org/10.1111/j.1463-1326.2010.01213.x] [PMID: 20590742]
[52]
Comparison of Insulin Tregopil (IN-105) with insulin aspart in type 2 diabetes mellitus patients. NCT03430856, 2019. Available from: https://clinicaltrials.gov/ct2/show/study/NCT03430856

[53]
Evaluation of pharmacokinetics, safety, tolerability and pharmacodynamics of biocon insulin tregopil. NCT04141423, 2019. Available from: https://clinicaltrials.gov/ct2/show/NCT04141423
[54]
Kidron, M. Methods and compositions for oral administration of proteins. U.S. Patent 9259456-B2, 2016.
[55]
Eldor, R.; Kidron, M.; Arbit, E. Open-label study to assess the safety and pharmacodynamics of five oral insulin formulations in healthy subjects. Diabetes Obes. Metab., 2010, 12(3), 219-223.
[http://dx.doi.org/10.1111/j.1463-1326.2009.01153.x] [PMID: 20151998]
[56]
A study to evaluate the efficacy and safety of ORMD-0801 (Oral Insulin) in patients with type 2 diabetes mellitus. NCT03467932, 2018. Available from: https://clinicaltrials.gov/ct2/show/NCT03467932
[57]
Eldor, R.; Fleming, G. A.; Neutel, J.; Homer, K. E.; Kidron, M.; Rosenstock, J. 1004-P: Oral Insulin (ORMD-0801) effects on glucose parameters in uncontrolled T2DM on OADs, 2020.
[58]
Eldor, R.; Neutel, J.; Homer, K.; Kidron, M. Efficacy and safety of 28‐day treatment with oral insulin (ORMD ‐0801) in patients with type 2 diabetes: A randomized, placebo‐controlled trial. Diabetes Obes. Metab., 2021, 23(11), 2529-2538.
[http://dx.doi.org/10.1111/dom.14499] [PMID: 34310011]
[59]
A phase 3 study to evaluate the efficacy and safety of ORMD-0801 in subjects with type 2 diabetes mellitus. NCT04754334, 2021. Available from: https://clinicaltrials.gov/ct2/show/NCT04754334
[60]
Malkov, D.; Angelo, R.; Wang, H.; Flanders, E.; Tang, H.; Gomez-Orellana, I. Oral delivery of insulin with the eligen technology: mechanistic studies. Curr. Drug Deliv., 2005, 2(2), 191-197.
[http://dx.doi.org/10.2174/1567201053586001] [PMID: 16305420]
[61]
Kidron, M.; Dinh, S.; Menachem, Y.; Abbas, R.; Variano, B.; Goldberg, M.; Arbit, E.; Bar-On, H. A novel per-oral insulin formulation: Proof of concept study in non-diabetic subjects. Diabet. Med., 2004, 21(4), 354-357.
[http://dx.doi.org/10.1111/j.1464-5491.2004.01160.x] [PMID: 15049938]
[62]
Heise, T.; Kapitza, C.; Nosek, L. Oral insulin as first-line therapy in type 2 diabetes: A randomized controlled pilot study. Diabetologia, 2004, 47(Suppl. 1), A5.
[63]
Novo Nordisk.. Novo Nordisk to acquire Emisphere Technologies and obtain ownership of the Eligen® SNAC oral delivery technology. 2020. Available from: https://www.novonordisk.com/newsand- media/news-and-ir-materials/news-details.html?id=33374
[64]
Geho, W.B.; Rosenberg, L.N.; Schwartz, S.L.; Lau, J.R.; Gana, T.J. A single-blind, placebo-controlled, dose-ranging trial of oral hepatic-directed vesicle insulin add-on to oral antidiabetic treatment in patients with type 2 diabetes mellitus. J. Diabetes Sci. Technol., 2014, 8(3), 551-559.
[http://dx.doi.org/10.1177/1932296814524871] [PMID: 24876619]
[65]
Geho, W.B.; Geho, H.C.; Lau, J.R.; Gana, T.J. Hepatic-directed vesicle insulin: A review of formulation development and preclinical evaluation. J. Diabetes Sci. Technol., 2009, 3(6), 1451-1459.
[http://dx.doi.org/10.1177/193229680900300627] [PMID: 20144401]
[66]
Diasome Pipeline.. 2022. Available from: https://www.diasome.com/
[67]
Lebovitz, H.E.; Fleming, A.; Cherrington, A.D. Efficacy and safety of tregopil, a novel, ultra-rapid acting oral prandial insulin analog, as part of a basal-bolus regimen in type 2 diabetes: A randomized, active controlled phase 3 study. medRxiv, 2022.
[http://dx.doi.org/10.1101/2022.02.15.22270708]
[68]
Study of two doses of oral HDV-insulin and placebo with background metformin treatment in patients with type 2 diabetes mellitus. NCT00814294, 2009. Available from: https://clinicaltrials.gov/ct2/show/NCT00814294
[69]
Comparison of Hepatic Directed Vesicle (HDV)-insulin lispro versus insulin lispro to further improve glycemic control. NCT03096392, 2018. Available from: https://clinicaltrials.gov/ct2/show/NCT03096392
[70]
Kim, E.S.; Plosker, G.L. AFREZZA® (insulin human) inhalation powder: A review in diabetes mellitus. Drugs, 2015, 75(14), 1679-1686.
[http://dx.doi.org/10.1007/s40265-015-0472-0] [PMID: 26384673]
[71]
MannKind Corporation.. Afrezza. 2014. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/022472 Orig1s000Lbl.pdf
[72]
Aerami Therapeutics.. Proprietary Inhalation Technology- The AFINA Experience. 2022. Available from: https://aerami.com/inhalation-technology/
[73]
Pharmacologic response and safety of inhaled insulin in type 1 diabetes (Samba-01). 2013. Available from: https://clinicaltrials.gov/ct2/show/NCT02713841
[74]
Tuan-Mahmood, T.M.; McCrudden, M.T.C.; Torrisi, B.M.; McAlister, E.; Garland, M.J.; Singh, T.R.R.; Donnelly, R.F. Microneedles for intradermal and transdermal drug delivery. Eur. J. Pharm. Sci., 2013, 50(5), 623-637.
[http://dx.doi.org/10.1016/j.ejps.2013.05.005] [PMID: 23680534]
[75]
NanoPass Technologies. MicronJet 600. 2010. Available from: http://www.accessdata.fda.gov/cdrh_docs/pdf9/K092746.pdf
[76]
Soares, S.; Costa, A.; Sarmento, B. Novel non-invasive methods of insulin delivery. Expert Opin. Drug Deliv., 2012, 9(12), 1539-1558.
[http://dx.doi.org/10.1517/17425247.2012.737779] [PMID: 23098366]
[77]
Transdermal specialties.. Seeking volunteers for a diabetes clinical trial. 2022. Available from: http://u-strip.com/index.php/clinicaltrial/
[78]
Zealand Pharma. How V-Go ® works. 2022. Available from: https://www.go-vgo.com/how-v-go-works/what-is-v-go/
[79]
U.S. FDA website valeritas V-Go ™ insulin delivery device. 2010. Available from: https://www.accessdata.fda.gov/cdrh_docs/pdf10/K103825.pdf
[80]
Patton, J.S.; Byron, P.R. Inhaling medicines: Delivering drugs to the body through the lungs. Nat. Rev. Drug Discov., 2007, 6(1), 67-74.
[http://dx.doi.org/10.1038/nrd2153] [PMID: 17195033]
[81]
Gänsslen, M. Uber inhalation von insulin. Klin. Wochenschr., 1925, 4(2), 71.
[http://dx.doi.org/10.1007/BF01748135]
[82]
Patton, J.S. Mechanisms of macromolecule absorption by the lungs. Adv. Drug Deliv. Rev., 1996, 19(1), 3-36.
[http://dx.doi.org/10.1016/0169-409X(95)00113-L]
[83]
Patton, J.S.; Fishburn, C.S.; Weers, J.G. The lungs as a portal of entry for systemic drug delivery. Proc. Am. Thorac. Soc., 2004, 1(4), 338-344.
[http://dx.doi.org/10.1513/pats.200409-049TA] [PMID: 16113455]
[84]
Bosquillon, C.; Lombry, C.; Préat, V.; Vanbever, R. Influence of formulation excipients and physical characteristics of inhalation dry powders on their aerosolization performance. J. Control. Release, 2001, 70(3), 329-339.
[http://dx.doi.org/10.1016/S0168-3659(00)00362-X] [PMID: 11182203]
[85]
Labiris, N.R.; Dolovich, M.B. Pulmonary drug delivery. Part I: Physiological factors affecting therapeutic effectiveness of aerosolized medications. Br. J. Clin. Pharmacol., 2003, 56(6), 588-599.
[http://dx.doi.org/10.1046/j.1365-2125.2003.01892.x] [PMID: 14616418]
[86]
Anderson, P.J. History of aerosol therapy: Liquid nebulization to MDIs to DPIs. Respir. Care, 2005, 50(9), 1139-1150.
[PMID: 16122398]
[87]
Geller, D.E. Comparing clinical features of the nebulizer, metered-dose inhaler, and dry powder inhaler. Respir. Care, 2005, 50(10), 1313-1321.
[PMID: 16185367]
[88]
Nikjoo, D.; van der Zwaan, I.; Brülls, M.; Tehler, U.; Frenning, G. Hyaluronic acid hydrogels for controlled pulmonary drug delivery—a particle engineering approach. Pharmaceutics, 2021, 13(11), 1878-1898.
[http://dx.doi.org/10.3390/pharmaceutics13111878] [PMID: 34834293]
[89]
Xia, Y.; Su, Y.; Wang, Q.; Yang, C.; Tang, B.; Zhang, Y.; Tu, J.; Shen, Y. Preparation, characterization, and pharmacodynamics of insulin-loaded fumaryl diketopiperazine microparticle dry powder inhalation. Drug Deliv., 2019, 26(1), 650-660.
[http://dx.doi.org/10.1080/10717544.2019.1631408] [PMID: 31257946]
[90]
Lin, X.F.; Kankala, R.K.; Tang, N.; Xu, P.Y.; Hao, L.Z.; Yang, D.Y.; Wang, S.B.; Zhang, Y.S.; Chen, A.Z. Supercritical fluid‐assisted porous microspheres for efficient delivery of insulin and inhalation therapy of diabetes. Adv. Healthc. Mater., 2019, 8(12), 1800910.
[http://dx.doi.org/10.1002/adhm.201800910] [PMID: 30284409]
[91]
Quarta, E.; Chierici, V.; Flammini, L.; Tognolini, M.; Barocelli, E.; Cantoni, A.M.; Dujovny, G.; Ecenarro Probst, S.; Sonvico, F.; Colom-bo, G.; Rossi, A.; Bettini, R.; Colombo, P.; Buttini, F. Excipient-free pulmonary insulin dry powder: Pharmacokinetic and pharmacodynamics profiles in rats. J. Control. Release, 2020, 323, 412-420.
[http://dx.doi.org/10.1016/j.jconrel.2020.04.015] [PMID: 32325175]
[92]
Harper, N.J.; Gray, S.; Groot, J.D. The design and performance of the Exubera® pulmonary insulin delivery system. Diabetes Technol. Ther., 2007, 9(S1), 27.
[93]
U.S. FDA website. Pfizer Global Research & Development. Exubera. 2006. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021868 s000_Lbl.pdf
[94]
Cefalu, W.T.; Skyler, J.S.; Kourides, I.A.; Landschulz, W.H.; Balagtas, C.C.; Cheng, S.L.; Gelfand, R.A. Inhaled human insulin treatment in patients with type 2 diabetes mellitus. Ann. Intern. Med., 2001, 134(3), 203-207.
[http://dx.doi.org/10.7326/0003-4819-134-3-200102060-00011] [PMID: 11177333]
[95]
Rave, K.; Bott, S.; Heinemann, L.; Sha, S.; Becker, R.H.A.; Willavize, S.A.; Heise, T. Time-action profile of inhaled insulin in comparison with subcutaneously injected insulin lispro and regular human insulin. Diabetes Care, 2005, 28(5), 1077-1082.
[http://dx.doi.org/10.2337/diacare.28.5.1077] [PMID: 15855570]
[96]
Quattrin, T.; Bélanger, A.; Bohannon, N.J.V.; Schwartz, S.L. Efficacy and safety of inhaled insulin (Exubera) compared with subcutaneous insulin therapy in patients with type 1 diabetes: Results of a 6-month, randomized, comparative trial. Diabetes Care, 2004, 27(11), 2622-2627.
[http://dx.doi.org/10.2337/diacare.27.11.2622] [PMID: 15504996]
[97]
Hollander, P.A.; Blonde, L.; Rowe, R.; Mehta, A.E.; Milburn, J.L.; Hershon, K.S.; Chiasson, J.L.; Levin, S.R. Efficacy and safety of in-haled insulin (exubera) compared with subcutaneous insulin therapy in patients with type 2 diabetes: Results of a 6-month, randomized, comparative trial. Diabetes Care, 2004, 27(10), 2356-2362.
[http://dx.doi.org/10.2337/diacare.27.10.2356] [PMID: 15451900]
[98]
Mack, G.S. Pfizer dumps Exubera. Nat. Biotechnol., 2007, 25(12), 1331-1332.
[http://dx.doi.org/10.1038/nbt1207-1331] [PMID: 18066009]
[99]
Pfützner, A.; Forst, T. Pulmonary insulin delivery by means of the Technosphere™ drug carrier mechanism. Expert Opin. Drug Deliv., 2005, 2(6), 1097-1106.
[http://dx.doi.org/10.1517/17425247.2.6.1097] [PMID: 16296812]
[100]
Steiner, S.; Pfützner, A.; Wilson, B.; Harzer, O.; Heinemann, L.; Rave, K.; Technosphere, T.M. Insulin - proof of concept study with a new insulin formulation for pulmonary delivery. Exp. Clin. Endocrinol. Diabetes, 2002, 110(1), 17-21.
[http://dx.doi.org/10.1055/s-2002-19989] [PMID: 11835120]
[101]
Rave, K.M.; Heise, T.; Pfützner, A.; Steiner, S.; Heinemann, L. Results of a dose-response study with a new pulmonary insulin formulation and inhaler. Diabetes, 2000, 49(5), A75.
[102]
Pfützner, A.; Heise, T.; Steiner, S.; Heinemann, L.; Rave, K. Inhaled technosphere/insulin shows a low variability in metabolic action in type 2 diabetic patients. Diabetes, 2000, 49(5), A121.
[103]
Rosenstock, J.; Baughman, R.A.; Rivera-Schaub, T.; Otterbach, K. A randomized, double-blind, placebo-controlled study of the efficacy and safety of inhaled Technosphere® insulin in patients with type 2 diabetes (T2DM). Diabetes, 2005, 54, A88.
[104]
Rosenstock, J.; Franco, D.; Korpachev, V.; Shumel, B.; Ma, Y.; Baughman, R.; Amin, N.; McGill, J.B. Inhaled Technosphere insulin versus inhaled Technosphere placebo in insulin-naïve subjects with type 2 diabetes inadequately controlled on oral antidiabetes agents. Diabetes Care, 2015, 38(12), 2274-2281.
[http://dx.doi.org/10.2337/dc15-0629] [PMID: 26253730]
[105]
Bode, B.W.; McGill, J.B.; Lorber, D.L.; Gross, J.L.; Chang, P.C.; Bregman, D.B. Inhaled technosphere insulin compared with injected prandial insulin in type 1 diabetes: A randomized 24-week trial. Diabetes Care, 2015, 38(12), 2266-2273.
[http://dx.doi.org/10.2337/dc15-0075] [PMID: 26180109]
[106]
Zijlstra, E.; Plum-Moerschel, L.; Ermer, M. 1085-P: Dance 501 Inhaled Human Insulin (INH): Linear Dose Response, Earlier Onset of Action, and Higher Early Effect than sc Insulin Lispro (LIS). Diabetes, 2019, 68(Suppl 1)
[107]
Ziljlstra, E.; Andersen, G.; Plum-Moerschel, L 1019-P: Variability of 501 inhaled insulin absorption and action. Diabetes, 2020, 69(Suppl 1)
[108]
Aerami Therapeutics. Pipeline. 2022. Available from: https://aerami.com/pipeline/
[109]
Kolarsick, P.A.J.; Kolarsick, M.A.; Goodwin, C. Anatomy and physiology of the skin. J. Dermatol. Nurses Assoc., 2011, 3(4), 203-213.
[http://dx.doi.org/10.1097/JDN.0b013e3182274a98]
[110]
Anselmo, A.C.; Gokarn, Y.; Mitragotri, S. Non-invasive delivery strategies for biologics. Nat. Rev. Drug Discov., 2019, 18(1), 19-40.
[http://dx.doi.org/10.1038/nrd.2018.183] [PMID: 30498202]
[111]
Prausnitz, M.R.; Langer, R. Transdermal drug delivery. Nat. Biotechnol., 2008, 26(11), 1261-1268.
[http://dx.doi.org/10.1038/nbt.1504] [PMID: 18997767]
[112]
Bouwstra, J.A.; Ponec, M. The skin barrier in healthy and diseased state. Biochim. Biophys. Acta Biomembr., 2006, 1758(12), 2080-2095.
[http://dx.doi.org/10.1016/j.bbamem.2006.06.021] [PMID: 16945325]
[113]
Arora, A.; Prausnitz, M.R.; Mitragotri, S. Micro-scale devices for transdermal drug delivery. Int. J. Pharm., 2008, 364(2), 227-236.
[http://dx.doi.org/10.1016/j.ijpharm.2008.08.032] [PMID: 18805472]
[114]
Sinha, V.R.; Kaur, M.P. Permeation enhancers for transdermal drug delivery. Drug Dev. Ind. Pharm., 2000, 26(11), 1131-1140.
[http://dx.doi.org/10.1081/DDC-100100984] [PMID: 11068686]
[115]
Pillai, O.; Nair, V.; Panchagnula, R. Transdermal iontophoresis of insulin: IV. Influence of chemical enhancers. Int. J. Pharm., 2004, 269(1), 109-120.
[http://dx.doi.org/10.1016/j.ijpharm.2003.09.032] [PMID: 14698582]
[116]
Marepally, S.; Boakye, C.H.A.; Shah, P.P.; Etukala, J.R.; Vemuri, A.; Singh, M. Design, synthesis of novel lipids as chemical permeation enhancers and development of nanoparticle system for transdermal drug delivery. PLoS One, 2013, 8(12), e82581.
[http://dx.doi.org/10.1371/journal.pone.0082581] [PMID: 24349315]
[117]
Tahara, Y.; Honda, S.; Kamiya, N.; Goto, M. Transdermal delivery of insulin using a solid-in-oil nanodispersion enhanced by arginine-rich peptides. MedChemComm, 2012, 3(12), 1496-1499.
[http://dx.doi.org/10.1039/c2md20059g]
[118]
Higaki, M.; Kameyama, M.; Udagawa, M.; Ueno, Y.; Yamaguchi, Y.; Igarashi, R.; Ishihara, T.; Mizushima, Y. Transdermal delivery of CaCO3-nanoparticles containing insulin. Diabetes Technol. Ther., 2006, 8(3), 369-374.
[http://dx.doi.org/10.1089/dia.2006.8.369] [PMID: 16800758]
[119]
Kováčik, A.; Kopečná, M.; Vávrová, K. Permeation enhancers in transdermal drug delivery: Benefits and limitations. Expert Opin. Drug Deliv., 2020, 17(2), 145-155.
[http://dx.doi.org/10.1080/17425247.2020.1713087] [PMID: 31910342]
[120]
Banerjee, A.; Ibsen, K.; Iwao, Y.; Zakrewsky, M.; Mitragotri, S. Transdermal protein delivery using choline and geranate (CAGE) deep eutectic solvent. Adv. Healthc. Mater., 2017, 6(15), 1601411.
[http://dx.doi.org/10.1002/adhm.201601411] [PMID: 28337858]
[121]
Zakrewsky, M.; Lovejoy, K.S.; Kern, T.L.; Miller, T.E.; Le, V.; Nagy, A.; Goumas, A.M.; Iyer, R.S.; Del Sesto, R.E.; Koppisch, A.T.; Fox, D.T.; Mitragotri, S. Ionic liquids as a class of materials for transdermal delivery and pathogen neutralization. Proc. Natl. Acad. Sci. USA, 2014, 111(37), 13313-13318.
[http://dx.doi.org/10.1073/pnas.1403995111] [PMID: 25157174]
[122]
Zakrewsky, M.; Banerjee, A.; Apte, S.; Kern, T.L.; Jones, M.R.; Sesto, R.E.D.; Koppisch, A.T.; Fox, D.T.; Mitragotri, S. Choline and geranate deep eutectic solvent as a broad‐spectrum antiseptic agent for preventive and therapeutic applications. Adv. Healthc. Mater., 2016, 5(11), 1282-1289.
[http://dx.doi.org/10.1002/adhm.201600086] [PMID: 26959835]
[123]
Saroha, K.; Yadav, B.; Sharma, B. Transdermal patch: A discrete dosage form. Int. J. Curr. Pharm. Res., 2011, 3(3), 98-108.
[124]
Prausnitz, M.R.; Mitragotri, S.; Langer, R. Current status and future potential of transdermal drug delivery. Nat. Rev. Drug Discov., 2004, 3(2), 115-124.
[http://dx.doi.org/10.1038/nrd1304] [PMID: 15040576]
[125]
Li, Y.; Yang, J.; Zheng, Y.; Ye, R.; Liu, B.; Huang, Y.; Zhou, W.; Jiang, L. Iontophoresis-driven porous microneedle array patch for active transdermal drug delivery. Acta Biomater., 2021, 121, 349-358.
[http://dx.doi.org/10.1016/j.actbio.2020.12.023] [PMID: 33340733]
[126]
Bariya, S.H.; Gohel, M.C.; Mehta, T.A.; Sharma, O.P. Microneedles: An emerging transdermal drug delivery system. J. Pharm. Pharmacol., 2011, 64(1), 11-29.
[http://dx.doi.org/10.1111/j.2042-7158.2011.01369.x] [PMID: 22150668]
[127]
Jeong, H.R.; Lee, H.S.; Choi, I.J.; Park, J.H. Considerations in the use of microneedles: Pain, convenience, anxiety and safety. J. Drug Target., 2017, 25(1), 29-40.
[http://dx.doi.org/10.1080/1061186X.2016.1200589] [PMID: 27282644]
[128]
Martanto, W.; Davis, S.P.; Holiday, N.R.; Wang, J.; Gill, H.S.; Prausnitz, M.R. Transdermal delivery of insulin using microneedles in vivo. Pharm. Res., 2004, 21(6), 947-952.
[http://dx.doi.org/10.1023/B:PHAM.0000029282.44140.2e] [PMID: 15212158]
[129]
Davis, S.P.; Martanto, W.; Allen, M.G.; Prausnitz, M.R. Hollow metal microneedles for insulin delivery to diabetic rats. IEEE Trans. Biomed. Eng., 2005, 52(5), 909-915.
[http://dx.doi.org/10.1109/TBME.2005.845240] [PMID: 15887540]
[130]
Ito, Y.; Nakahigashi, T.; Yoshimoto, N.; Ueda, Y.; Hamasaki, N.; Takada, K. Transdermal insulin application system with dissolving microneedles. Diabetes Technol. Ther., 2012, 14(10), 891-899.
[http://dx.doi.org/10.1089/dia.2012.0096] [PMID: 23013202]
[131]
Yu, J.; Zhang, Y.; Ye, Y.; DiSanto, R.; Sun, W.; Ranson, D.; Ligler, F.S.; Buse, J.B.; Gu, Z. Microneedle-array patches loaded with hypoxia-sensitive vesicles provide fast glucose-responsive insulin delivery. Proc. Natl. Acad. Sci. USA, 2015, 112(27), 8260-8265.
[http://dx.doi.org/10.1073/pnas.1505405112] [PMID: 26100900]
[132]
Zhang, Y.; Wang, J.; Yu, J.; Wen, D.; Kahkoska, A.R.; Lu, Y.; Zhang, X.; Buse, J.B.; Gu, Z. Bioresponsive microneedles with a sheath structure for H 2 O 2 and pH cascade‐triggered insulin delivery. Small, 2018, 14(14), 1704181.
[http://dx.doi.org/10.1002/smll.201704181] [PMID: 29479811]
[133]
Ye, Y.; Yu, J.; Wang, C.; Nguyen, N.Y.; Walker, G.M.; Buse, J.B.; Gu, Z. Microneedles integrated with pancreatic cells and synthetic glucose‐signal amplifiers for smart insulin delivery. Adv. Mater., 2016, 28(16), 3115-3121.
[http://dx.doi.org/10.1002/adma.201506025] [PMID: 26928976]
[134]
Yu, J.; Wang, J.; Zhang, Y.; Chen, G.; Mao, W.; Ye, Y.; Kahkoska, A.R.; Buse, J.B.; Langer, R.; Gu, Z. Glucose-responsive insulin patch for the regulation of blood glucose in mice and minipigs. Nat. Biomed. Eng., 2020, 4(5), 499-506.
[http://dx.doi.org/10.1038/s41551-019-0508-y] [PMID: 32015407]
[135]
Fonseca, D.F.S.; Costa, P.C.; Almeida, I.F.; Dias-Pereira, P.; Correia-Sá, I.; Bastos, V.; Oliveira, H.; Duarte-Araújo, M.; Morato, M.; Vilela, C.; Silvestre, A.J.D.; Freire, C.S.R. Pullulan microneedle patches for the efficient transdermal administration of insulin envisioning diabetes treatment. Carbohydr. Polym., 2020, 241, 116314.
[http://dx.doi.org/10.1016/j.carbpol.2020.116314] [PMID: 32507191]
[136]
Kalia, Y.N.; Naik, A.; Garrison, J.; Guy, R.H. Iontophoretic drug delivery. Adv. Drug Deliv. Rev., 2004, 56(5), 619-658.
[http://dx.doi.org/10.1016/j.addr.2003.10.026] [PMID: 15019750]
[137]
Park, D.; Park, H.; Seo, J.; Lee, S. Sonophoresis in transdermal drug deliverys. Ultrasonics, 2014, 54(1), 56-65.
[http://dx.doi.org/10.1016/j.ultras.2013.07.007] [PMID: 23899825]
[138]
Smith, N.B.; Lee, S.; Maione, E.; Roy, R.B.; McElligott, S.; Shung, K.K. Ultrasound-mediated transdermal transport of insulin in vitro through human skin using novel transducer designs. Ultrasound Med. Biol., 2003, 29(2), 311-317.
[http://dx.doi.org/10.1016/S0301-5629(02)00706-8] [PMID: 12659919]
[139]
Smith, N.B.; Lee, S.; Shung, K.K. Ultrasound-mediated transdermal in vivo transport of insulin with low-profile cymbal arrays. Ultrasound Med. Biol., 2003, 29(8), 1205-1210.
[http://dx.doi.org/10.1016/S0301-5629(03)00908-6] [PMID: 12946523]
[140]
Mitragotri, S. Devices for overcoming biological barriers: The use of physical forces to disrupt the barriers. Adv. Drug Deliv. Rev., 2013, 65(1), 100-103.
[http://dx.doi.org/10.1016/j.addr.2012.07.016] [PMID: 22960787]
[141]
Egelrud, T. Desquamation in the stratum corneum. Acta Derm. Venereol., 2000.
[142]
Lee, J.W.; Gadiraju, P.; Park, J.H.; Allen, M.G.; Prausnitz, M.R. Microsecond thermal ablation of skin for transdermal drug delivery. J. Control. Release, 2011, 154(1), 58-68.
[http://dx.doi.org/10.1016/j.jconrel.2011.05.003] [PMID: 21596072]
[143]
Fang, J.Y.; Lee, W.R.; Shen, S.C.; Wang, H.Y.; Fang, C.L.; Hu, C.H. Transdermal delivery of macromolecules by erbium:YAG laser. J. Control. Release, 2004, 100(1), 75-85.
[http://dx.doi.org/10.1016/j.jconrel.2004.08.009] [PMID: 15491812]
[144]
Zhang, Y.; Chai, D.; Gao, M.; Xu, B.; Jiang, G. Thermal ablation of separable microneedles for transdermal delivery of metformin on diabetic rats. Int. J. Polym. Mater., 2019, 68(14), 850-858.
[http://dx.doi.org/10.1080/00914037.2018.1517347]
[145]
Harjoh, N.; Wong, T.W.; Caramella, C. Transdermal insulin delivery with microwave and fatty acids as permeation enhancers. Int. J. Pharm., 2020, 584, 119416.
[http://dx.doi.org/10.1016/j.ijpharm.2020.119416] [PMID: 32423875]
[146]
Yu, W.; Jiang, G.; Liu, D.; Li, L.; Tong, Z.; Yao, J.; Kong, X. Transdermal delivery of insulin with bioceramic composite microneedles fabricated by gelatin and hydroxyapatite. Mater. Sci. Eng. C, 2017, 73, 425-428.
[http://dx.doi.org/10.1016/j.msec.2016.12.111] [PMID: 28183628]
[147]
Xenikakis, I.; Tsongas, K.; Tzimtzimis, E.K. Transdermal delivery of insulin across human skin in vitro with 3D printed hollow microneedles. J. Drug Deliv. Sci. Technol., 2021, 102891.
[148]
Islam, M.R.; Uddin, S.; Chowdhury, M.R.; Wakabayashi, R.; Moniruzzaman, M.; Goto, M. Insulin Transdermal Delivery System for Diabetes Treatment Using a Biocompatible Ionic Liquid-Based Microemulsion. ACS Appl. Mater. Interfaces, 2021, 13(36), 42461-42472.
[http://dx.doi.org/10.1021/acsami.1c11533] [PMID: 34460218]
[149]
Zhang, N.; Zhou, X.; Liu, L.; Zhao, L.; Xie, H.; Yang, Z. Dissolving polymer microneedles for transdermal delivery of insulin. Front. Pharmacol., 2021, 12, 719905.
[http://dx.doi.org/10.3389/fphar.2021.719905] [PMID: 34630098]
[150]
Zou, J.J.; Le, J.Q.; Zhang, B.C.; Yang, M.Y.; Jiang, J.L.; Lin, J.F.; Wu, P.Y.; Li, C.; Chen, L.; Shao, J.W. Accelerating transdermal delivery of insulin by ginsenoside nanoparticles with unique permeability. Int. J. Pharm., 2021, 605, 120784.
[http://dx.doi.org/10.1016/j.ijpharm.2021.120784] [PMID: 34111544]
[151]
Kochba, E.; Levin, Y.; Raz, I.; Cahn, A. Improved insulin pharmacokinetics using a novel microneedle device for intradermal delivery in patients with type 2 diabetes. Diabetes Technol. Ther., 2016, 18(9), 525-531.
[http://dx.doi.org/10.1089/dia.2016.0156] [PMID: 27500713]
[152]
Gupta, J.; Felner, E.I.; Prausnitz, M.R. Rapid pharmacokinetics of intradermal insulin administered using microneedles in type 1 diabetes subjects. Diabetes Technol. Ther., 2011, 13(4), 451-456.
[http://dx.doi.org/10.1089/dia.2010.0204] [PMID: 21355717]
[153]
PassPort Technologies. PassPort® Novel Transdermal Drug Delivery System. 2022. Available from: https://passport-tech.com/
[154]
Transdermal basal insulin patch study in type 1 diabetes. NCT00519623, 2007. Available from: https://clinicaltrials.gov/ct2/show/results/NCT00519623
[155]
[156]
Redding, B.K. Designing an ultrasound-enabled patch for insulin. ON drug Delivery Magazine, 2014, 49, 22-26,
[157]
Kapitza, C.; Fein, S.; Heinemann, L.; Schleusener, D.; Levesque, S.; Strange, P. Basal-prandial insulin delivery in type 2 diabetes mellitus via the V-Go: A novel continuous subcutaneous infusion device. J. Diabetes Sci. Technol., 2008, 2(1), 40-46.
[http://dx.doi.org/10.1177/193229680800200107] [PMID: 19885176]
[158]
Sutton, D.; Higdon, C.D.; Nikkel, C.; Hilsinger, K.A. Clinical benefits over time associated with use of V-Go wearable insulin delivery device in adult patients with diabetes: A retrospective analysis. Adv. Ther., 2018, 35(5), 631-643.
[http://dx.doi.org/10.1007/s12325-018-0703-3] [PMID: 29748915]
[159]
Illum, L. Nasal drug delivery—possibilities, problems and solutions. J. Control. Release, 2003, 87(1-3), 187-198.
[http://dx.doi.org/10.1016/S0168-3659(02)00363-2] [PMID: 12618035]
[160]
Jadhav, K.; Gambhire, M.; Shaikh, I.; Kadam, V.; Pisal, S. Nasal drug delivery system-factors affecting and applications. Curr. Drug Ther., 2007, 2(1), 27-38.
[http://dx.doi.org/10.2174/157488507779422374]
[161]
Ugwoke, M.I.; Verbeke, N.; Kinget, R. The biopharmaceutical aspects of nasal mucoadhesive drug delivery. J. Pharm. Pharmacol., 2010, 53(1), 3-21.
[http://dx.doi.org/10.1211/0022357011775145] [PMID: 11206189]
[162]
Davis, S.S.; Illum, L. Absorption enhancers for nasal drug delivery. Clin. Pharmacokinet., 2003, 42(13), 1107-1128.
[http://dx.doi.org/10.2165/00003088-200342130-00003] [PMID: 14531723]
[163]
Sharma, M.; Waghela, S.; Mhatre, R.; Saraogi, G.K. A recent update on intranasal delivery of high molecular weight proteins, peptides, and hormones. Curr. Pharm. Des., 2021, 27(42), 4279-4299.
[http://dx.doi.org/10.2174/1381612827666210820100723] [PMID: 34414869]
[164]
Hinchcliffe, M.; Illum, L. Intranasal insulin delivery and therapy. Adv. Drug Deliv. Rev., 1999, 35(2-3), 199-234.
[http://dx.doi.org/10.1016/S0169-409X(98)00073-8] [PMID: 10837698]
[165]
Kim, N.A.; Thapa, R.; Jeong, S.H.; Bae, H.; Maeng, J.; Lee, K.; Park, K. Enhanced intranasal insulin delivery by formulations and tumor protein-derived protein transduction domain as an absorption enhancer. J. Control. Release, 2019, 294, 226-236.
[http://dx.doi.org/10.1016/j.jconrel.2018.12.023] [PMID: 30557648]
[166]
Li, Y.; Wu, X.; Zhu, Q.; Chen, Z.; Lu, Y.; Qi, J.; Wu, W. Improving the hypoglycemic effect of insulin via the nasal administration of deep eutectic solvents. Int. J. Pharm., 2019, 569, 118584.
[http://dx.doi.org/10.1016/j.ijpharm.2019.118584] [PMID: 31376466]
[167]
de Souza Von Zuben, E.; Eloy, J.O.; Araujo, V.H.S.; Gremião, M.P.D.; Chorilli, M. Insulin-loaded liposomes functionalized with cell-penetrating peptides: Influence on drug release and permeation through porcine nasal mucosa. Colloids Surf. A Physicochem. Eng. Asp., 2021, 622, 126624.
[http://dx.doi.org/10.1016/j.colsurfa.2021.126624]
[168]
Wei, X.; Duan, X.; Zhang, Y.; Ma, Z.; Li, C.; Zhang, X. Internalization mechanism of phenylboronic-acid-decorated nanoplatform for enhanced nasal insulin delivery. ACS Appl. Bio Mater., 2020, 3(4), 2132-2139.
[http://dx.doi.org/10.1021/acsabm.0c00002] [PMID: 35025265]
[169]
Serim, T.M.; Kožák, J.; Rautenberg, A.; Özdemir, A.N.; Pellequer, Y.; Lamprecht, A. Spray freeze dried lyospheres® for nasal administration of insulin. Pharmaceutics, 2021, 13(6), 852.
[http://dx.doi.org/10.3390/pharmaceutics13060852] [PMID: 34201254]
[170]
Gao, M.; Sun, Y.; Kou, Y.; Shen, X.; Huo, Y.; Liu, C.; Sun, Z.; Zhang, X.; Mao, S. Effect of glyceryl monocaprylate–modified chitosan on the intranasal absorption of insulin in rats. J. Pharm. Sci., 2019, 108(11), 3623-3629.
[http://dx.doi.org/10.1016/j.xphs.2019.07.012] [PMID: 31356762]
[171]
Rossi, S.; Sandri, G.; Caramella, C.M. Buccal drug delivery: A challenge already won? Drug Discov. Today. Technol., 2005, 2(1), 59-65.
[http://dx.doi.org/10.1016/j.ddtec.2005.05.018] [PMID: 24981756]
[172]
Squier, C.A.; Kremer, M.J. Biology of oral mucosa and esophagus. J. Natl. Cancer Inst. Monogr., 2001, 2001(29), 7-15.
[http://dx.doi.org/10.1093/oxfordjournals.jncimonographs.a003443] [PMID: 11694559]
[173]
Pather, S.I.; Rathbone, M.J.; Şenel, S. Current status and the future of buccal drug delivery systems. Expert Opin. Drug Deliv., 2008, 5(5), 531-542.
[http://dx.doi.org/10.1517/17425247.5.5.531] [PMID: 18491980]
[174]
Smart, J.D. Buccal drug delivery. Expert Opin. Drug Deliv., 2005, 2(3), 507-517.
[http://dx.doi.org/10.1517/17425247.2.3.507] [PMID: 16296771]
[175]
Mørck Nielsen, H.; Rømer Rassing, M. TR146 cells grown on filters as a model of human buccal epithelium: V. Enzyme activity of the TR146 cell culture model, human buccal epithelium and porcine buccal epithelium, and permeability of leu-enkephalin. Int. J. Pharm., 2000, 200(2), 261-270.
[http://dx.doi.org/10.1016/S0378-5173(00)00394-X] [PMID: 10867256]
[176]
Hao, J.; Heng, P.W.S. Buccal delivery systems. Drug Dev. Ind. Pharm., 2003, 29(8), 821-832.
[http://dx.doi.org/10.1081/DDC-120024178] [PMID: 14570303]
[177]
Şenel, S.; Hıncal, A.A. Drug permeation enhancement via buccal route: Possibilities and limitations. J. Control. Release, 2001, 72(1-3), 133-144.
[http://dx.doi.org/10.1016/S0168-3659(01)00269-3] [PMID: 11389992]
[178]
Veuillez, F.; Kalia, Y.N.; Jacques, Y.; Deshusses, J.; Buri, P. Factors and strategies for improving buccal absorption of peptides. Eur. J. Pharm. Biopharm., 2001, 51(2), 93-109.
[http://dx.doi.org/10.1016/S0939-6411(00)00144-2] [PMID: 11226816]
[179]
Bashyal, S.; Seo, J.E.; Keum, T.; Noh, G.; Choi, Y.W.; Lee, S. Facilitated permeation of insulin across TR146 cells by cholic acid derivatives-modified elastic bilosomes. Int. J. Nanomedicine, 2018, 13, 5173-5186.
[http://dx.doi.org/10.2147/IJN.S168310] [PMID: 30233179]
[180]
Herlofson, B.B.; Barkvoll, P. Desquamative effect of sodium lauryl sulfate on oral mucosa. A preliminary study. Acta Odontol. Scand., 1993, 51(1), 39-43.
[http://dx.doi.org/10.3109/00016359309041146] [PMID: 8451922]
[181]
Salamatmiller, N.; Chittchang, M.; Johnston, T. The use of mucoadhesive polymers in buccal drug delivery. Adv. Drug Deliv. Rev., 2005, 57(11), 1666-1691.
[http://dx.doi.org/10.1016/j.addr.2005.07.003] [PMID: 16183164]
[182]
Voronova, A.; Prieto, C.; Pardo-Figuerez, M.; Lagaron, J.M.; Sanyal, A.; Demir, B.; Hubert, T.; Plaisance, V.; Pawlowski, V.; Vignoud-Despond, S.; Barras, A.; Abderrahmani, A.; Boukherroub, R.; Szunerits, S. Photothermal activatable mucoadhesive fiber mats for on-demand delivery of insulin via buccal and corneal mucosa. ACS Appl. Bio Mater., 2022, 5(2), 771-778.
[http://dx.doi.org/10.1021/acsabm.1c01161] [PMID: 35026943]
[183]
Bozeya, A.; Al-Domi, D.; Al-Fandi, M. Development of an insulin nano-delivery system through buccal administration. Curr. Drug Deliv., 2022, 19(8), 889-901.
[http://dx.doi.org/10.2174/1567201819666220112121115] [PMID: 35023456]
[184]
Al-Remawi, M.; Jaber, N.; Elsayed, A.; Alsafadi, D.; Salah, K.A. Stabilization of insulin using low molecular weight chitosan carbonate nanocarrier. Carbohydr. Polym., 2022, 291, 119579.
[http://dx.doi.org/10.1016/j.carbpol.2022.119579] [PMID: 35698397]
[185]
Diab, M.; Sallam, A.S.; Hamdan, I.; Mansour, R.; Hussain, R.; Siligardi, G.; Qinna, N.; Khalil, E. Characterization of insulin mucoadhesive buccal films: Spectroscopic analysis and in vivo evaluation. Symmetry (Basel), 2021, 13(1), 88.
[http://dx.doi.org/10.3390/sym13010088]
[186]
Xu, Y.; Zhang, X.; Wang, N.; Pei, X.; Guo, Y.; Wang, J.; Barth, S.; Yu, F.; Lee, S.J.; He, H.; Yang, V.C. Cell-penetrating peptide enhanced insulin buccal absorption. Int. J. Pharm., 2020, 584, 119469.
[http://dx.doi.org/10.1016/j.ijpharm.2020.119469] [PMID: 32470482]
[187]
Bashyal, S.; Seo, J.E.; Keum, T.; Noh, G.; Lamichhane, S.; Lee, S. Development, characterization, and ex vivo assessment of elastic liposomes for enhancing the buccal delivery of insulin. Pharmaceutics, 2021, 13(4), 565.
[http://dx.doi.org/10.3390/pharmaceutics13040565] [PMID: 33923670]
[188]
Chou, W.H.; Galaz, A.; Jara, M.O.; Gamboa, A.; Morales, J.O. Drug-loaded lipid-core micelles in mucoadhesive films as a novel dosage form for buccal administration of poorly water-soluble and biological drugs. Pharmaceutics, 2020, 12(12), 1168.
[http://dx.doi.org/10.3390/pharmaceutics12121168] [PMID: 33266132]
[189]
Bashyal, S.; Seo, J.E.; Keum, T.; Noh, G.; Lamichhane, S.; Kim, J.H.; Kim, C.H.; Choi, Y.W.; Lee, S. Facilitated buccal insulin delivery via hydrophobic ion-pairing approach: In vitro and ex vivo evaluation. Int. J. Nanomedicine, 2021, 16, 4677-4691.
[http://dx.doi.org/10.2147/IJN.S318092] [PMID: 34262275]
[190]
Yang, Y.; Guo, Y.; Xu, Y.; Meng, Y.; Zhang, X.; Xia, X.; Liu, Y. Factors affecting the buccal delivery of deformable nanovesicles based on insulin–phospholipid complex: An in vivo investigation. Drug Deliv., 2020, 27(1), 900-908.
[http://dx.doi.org/10.1080/10717544.2020.1778814] [PMID: 32597266]
[191]
Vaidya, A.; Mitragotri, S. Ionic liquid-mediated delivery of insulin to buccal mucosa. J. Control. Release, 2020, 327, 26-34.
[http://dx.doi.org/10.1016/j.jconrel.2020.07.037] [PMID: 32735879]
[192]
Al-Nemrawi, N.K.; Alsharif, S.S.M.; Alzoubi, K.H.; Alkhatib, R.Q. Preparation and characterization of insulin chitosan-nanoparticles loaded in buccal films. Pharm. Dev. Technol., 2019, 24(8), 967-974.
[http://dx.doi.org/10.1080/10837450.2019.1619183] [PMID: 31092092]
[193]
Paprikar, A.; Soni, A.; Kaushal, N.; Lin, S. Sublingual insulin administration: application of hydroxypropyl beta-cyclodextrin and polox-amer188 as permeation enhancers. Pharm. Dev. Technol., 2021, 26(2), 233-242.
[http://dx.doi.org/10.1080/10837450.2020.1858319] [PMID: 33258391]
[194]
Goodson, N.; Wicks, P.; Morgan, J.; Hashem, L.; Callinan, S.; Reites, J. Opportunities and counterintuitive challenges for decentralized clinical trials to broaden participant inclusion. NPJ Digit. Med., 2022, 5(1), 58.
[http://dx.doi.org/10.1038/s41746-022-00603-y] [PMID: 35513479]
[195]
Paul, D.; Sanap, G.; Shenoy, S.; Kalyane, D.; Kalia, K.; Tekade, R.K. Artificial intelligence in drug discovery and development. Drug Discov. Today, 2021, 26(1), 80-93.
[http://dx.doi.org/10.1016/j.drudis.2020.10.010] [PMID: 33099022]
[196]
Mak, K.K.; Pichika, M.R. Artificial intelligence in drug development: Present status and future prospects. Drug Discov. Today, 2019, 24(3), 773-780.
[http://dx.doi.org/10.1016/j.drudis.2018.11.014] [PMID: 30472429]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy