Nose-to-brain delivery of insulin nanoparticles for diabetes management: A review
DOI:
https://doi.org/10.47419/bjbabs.v4i02.178Keywords:
diabetes, mucoadhesive, nanoparticles, nose-to-brainAbstract
Hyperglycemia and the onset of insulin resistance or deficiency, or both, are the hallmarks of the group of diseases known as diabetes. Ultimately, insulin subcutaneous injection is the most effective treatment for diabetic patients. However, most patients must self-administer insulin at least twice daily for the rest of their lives, as this form of administration is frequently uncomfortable and inconvenient. Infections, insulin precipitation, lipoatrophy, or lipohypertrophy are commonly observed at the injection site. To date, nasal, pulmonary, and oral methods of insulin administration have been explored. Although insulin stimulation is the ideal method for diabetic patients, there are several obstacles to overcome, such as rapid insulin degradation in the stomach and limited oral bioavailability. Various strategies have been approved to improve these parameters, including the use of enzyme inhibitors, mucoadhesive polymeric agents, absorption-enhancing agents, and chemical modifications. Insulin-loaded nanocarriers can bypass numerous physiological limitations. The current review discusses the approach of nanotechnology in nose-to-brain delivery of nanoparticles for diabetes management.
Downloads
References
Bialonska D, Zjawiony JK. Aplysinopsins-marine indole alkaloids: chem- istry, bioactivity and ecological significance. Mar Drugs. 2009;7(2):166–183. 10.3390/md7020166. DOI: https://doi.org/10.3390/md7020166
Shaji J, Patole V. Protein and peptide drug delivery: Oral approaches. Indian J Pharm Sci. 2008;70(3):269–269. 10.4103/0250-474X.42967. DOI: https://doi.org/10.4103/0250-474X.42967
Bruno BJ, Miller GD, Lim CS. Basics and recent advances in peptide and protein drug delivery. Ther Deliv. 2013;4(11):1443–1467. 10.4155/tde.13.104. DOI: https://doi.org/10.4155/tde.13.104
Luo YY, Xiong XY, Tian Y, Li ZL, Gong YC, Li YP, et al.. A review of biodegradable polymeric systems for oral insulin delivery.; 2016. 10.3109/10717544.2015.1052863. DOI: https://doi.org/10.3109/10717544.2015.1052863
Mansoor S, Kondiah P, Choonara YE, Pillay V, et al. Polymer-Based Nanoparticle Strategies for Insulin Delivery. Polymers (Basel). 2019;11(9). 10.3390/polym11091380. DOI: https://doi.org/10.3390/polym11091380
Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 2009;32(Supple- ment_1). 10.2337/dc09-S062. DOI: https://doi.org/10.2337/dc09-S062
Souto EB, Souto SB, Campos JR. Nanoparticle Delivery Systems in the Treatment of Diabetes Complications. Molecules. 2019;24(23):4209–4209. DOI: https://doi.org/10.3390/molecules24234209
Chenthamara D, Subramaniam S, Ramakrishnan SG. Therapeutic efficacy of nanoparticles and routes of administration. Biomater Res. 2019;23(1):20–20. 10.1186/s40824-019-0166-x. DOI: https://doi.org/10.1186/s40824-019-0166-x
Iqbal A, Novodvorsky P, Heller SR. Recent Updates on Type 1 Diabetes Mellitus Management for Clinicians. Diabetes Metab J. 2018;42(1):3–18. 10.4093/dmj.2018.42.1.3. DOI: https://doi.org/10.4093/dmj.2018.42.1.3
Sharma G, Sharma AR, Nam JS, Doss G, Lee SS, Chakraborty C, et al. Nanopar- ticle based insulin delivery system: the next generation efficient therapy for Type 1 diabetes. J Nanobiotechnology. 2015;13(1):74–74. 10.1186/s12951-015-0136-y. DOI: https://doi.org/10.1186/s12951-015-0136-y
Vantyghem MC, Press M. Management strategies for brittle diabetes. Ann Endocrinol (Paris). 2006;67(4):287–294. 10.1016/S0003-4266(06)72600-2. DOI: https://doi.org/10.1016/S0003-4266(06)72600-2
Dunning T, Martin P. Diabetes and palliative care: a framework to help clinicians proactively plan for personalized care. Palliative Care IntechOpen. 2019;10.5772/in- techopen.83534. DOI: https://doi.org/10.5772/intechopen.83534
Mergenthaler P, Lindauer U, Dienel GA, Meisel A, et al. Sugar for the brain: the role of glucose in physiological and pathological brain function. Trends in Neurosciences. 2013;36(10):587–597. 10.1016/j.tins.2013.07.001. DOI: https://doi.org/10.1016/j.tins.2013.07.001
Galicia-Garcia U, Benito-Vicente A, Jebari S. Pathophysiology of Type 2 Diabetes Mellitus. Journal of Molecular Sciences. 2020;21(17):6275–6275. DOI: https://doi.org/10.3390/ijms21176275
Plows J, Stanley J, Baker P, Reynolds C, Vickers M, et al. The pathophysi- ology of gestational diabetes mellitus. Int J Mol Sci. 2018;19(11):3342–3342. 10.3390/ijms19113342. DOI: https://doi.org/10.3390/ijms19113342
Röder PV, Wu B, Liu Y, Han W. Pancreatic regulation of glucose homeostasis. Exper- imental & Molecular Medicine. 2016;48(3):219–219. DOI: https://doi.org/10.1038/emm.2016.6
Fu Z, Gilbert ER, Liu D. Regulation of insulin synthesis and secretion and pancreatic Beta-cell dysfunction in diabetes. Curr Diabetes Rev. 2013;9(1):25–53. DOI: https://doi.org/10.2174/157339913804143225
Berger C, Zdzieblo D. Glucose transporters in pancreatic islets. Pflugers Arch PFLUG ARCH EUR J PHY. 2020;472(9):1249–1272. 10.1007/s00424-020-02383-4. DOI: https://doi.org/10.1007/s00424-020-02383-4
Wilcox G. Insulin and insulin resistance. Clin Biochem Rev. 2005;26(2):19–39.
Thrower SL, Bingley PJ. What is type 1 diabetes?; 2014. 10.1016/j.mpmed.2010.08.003. DOI: https://doi.org/10.1016/j.mpmed.2014.09.003
Daneman D. Type 1 diabetes.; 2006. 10.1016/S0140-6736(06)68341-4. DOI: https://doi.org/10.1016/S0140-6736(06)68341-4
Atkinson MA, Eisenbarth GS, Michels AW. Type 1 diabetes; 2014. 10.1016/S0140- 6736(13)60591-7.
Olokoba AB, Obateru OA, Olokoba LB. Type 2 diabetes mellitus: a review of current trends. Oman Med J. 2012;27(4):269–273. 10.5001/omj.2012.68. DOI: https://doi.org/10.5001/omj.2012.68
Solis-Herrera C, Triplitt C, Cersosimo E, Defronzo RA, et al. Pathogenesis of Type 2 Diabetes Mellitus. Endotext. 2000;Available from: http://www.ncbi.nlm.nih.gov/ pubmed/25905339.
Deshpande AD, Harris-Hayes M, Schootman M. Epidemiology of dia- betes and diabetes-related complications. Phys Ther. 2008;88(11):1254–1264. 10.2522/ptj.20080020. DOI: https://doi.org/10.2522/ptj.20080020
Virani SS, Alonso A, Aparicio HJ, et al. Heart Disease and Stroke Statistics-2021 Update: A Report From the American Heart Association. Circulation. 2021;143(8). 10.1161/CIR.0000000000000950.
Karter AJ, Lipska KJ, Connor O, J P, et al. High rates of severe hypoglycemia among African American patients with diabetes: the surveillance, prevention, and Man- agement of Diabetes Mellitus (SUPREME-DM) network. J Diabetes Complicat. 2017;31(5):869–873. 10.1016/j.jdiacomp.2017.02.009. DOI: https://doi.org/10.1016/j.jdiacomp.2017.02.009
Amed S, Dean HJ, Panagiotopoulos C, et al. Type 2 diabetes, medication-induced diabetes, and monogenic diabetes in Canadian children: A prospective national surveillance study. Diabetes Care. 2010;33(4):786–791. 10.2337/dc09-1013. DOI: https://doi.org/10.2337/dc09-1013
Chaudhury A, Duvoor C, Dendi R, S V, et al. Clinical review of antidiabetic drugs: implications for type 2 diabetes melitus management. . Front Endocrinol. 2017;8. 10.3389/fendo.2017.00006. DOI: https://doi.org/10.3389/fendo.2017.00006
George MM, Copeland KC. Current treatment options for type 2 diabetes melli- tus in youth: today’s realities and lessons from the TODAY study. Curr Diab Rep. 2013;13(1):72–80. 10.1007/s11892-012-0334-z. DOI: https://doi.org/10.1007/s11892-012-0334-z
Inzucchi SE, Lipska KJ, Mayo H, Bailey CJ, Mcguire DK, et al. Metformin in patients with type 2 diabetes and kidney disease: a systematic review. JAMA. 2014;312(24):2668–2675. 10.1001/jama.2014.15298. DOI: https://doi.org/10.1001/jama.2014.15298
Wadden TA, Webb VL, Moran CH, Bailer BA, et al. 10.1161/CIRCULATION- AHA.111.039453. Circulation. 2012;125(9):1157–1170. 10.1161/CIRCULATION- AHA.111.039453. DOI: https://doi.org/10.1161/CIRCULATIONAHA.111.039453
Nolan CJ, Damm P, Prentki M. Type 2 diabetes across generations: from pathophys- iology to prevention and management. ; 2011. 10.1016/S0140-6736(11)60614-4. DOI: https://doi.org/10.1016/S0140-6736(11)60614-4
Defronzo RA. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus (banting lecture). Diabetes. 2009;58(4):773– 795. 10.2337/db09-9028. DOI: https://doi.org/10.2337/db09-9028
Goran MI, Gower BA. Longitudinal study on pubertal insulin resistance. Diabetes. 2001;50(11). 10.2337/diabetes.50.11.2444. DOI: https://doi.org/10.2337/diabetes.50.11.2444
Onge E, St, Miller SA, Motycka C, Deberry A, et al. A review of the treatment of type 2 diabetes in children. J Pediatr Pharmacol Ther. 2015;20(1):4–16. 10.5863/1551- 6776-20.1.4. DOI: https://doi.org/10.5863/1551-6776-20.1.4
Bloomgarden Z, Hba1c B. Beyond HbA1c. J Diabetes. 2017;9(12):1052–1053. 10.1111/1753-0407.12590. DOI: https://doi.org/10.1111/1753-0407.12590
Vos FE, Schollum JB, Coulter CV, Manning PJ, Duffull SB, Walker RJ, et al. Assess- ment of markers of glycaemic control in diabetic patients with chronic kidney disease using continuous glucose monitoring. Nephrology. 2012;17(2):182–188. 10.1111/j.1440-1797.2011.01517.x. DOI: https://doi.org/10.1111/j.1440-1797.2011.01517.x
Djupesland PG, Gisle P. asal drug delivery devices: characteristics and perfor- mance in a clinical perspective—a review. Drug Deliv Transl Res. 2013;3(1):42–62. 10.1007/s13346-012-0108-9. DOI: https://doi.org/10.1007/s13346-012-0108-9
Trevino JT, Quispe RC, Khan F, Novak V, et al. Non-invasive strategies for nose-to brain drug delivery. J Clin Trials. 2020;10(7).
Agrawal M, Saraf S, Saraf S. Nose-to-brain drug delivery: An update on clinical challenges and progress towards approval of anti-Alzheimer drugs. J Control Release. 2018;281:139–177. 10.1016/j.jconrel.2018.05.011. DOI: https://doi.org/10.1016/j.jconrel.2018.05.011
Gori A, Leone F, Loffredo L. COVID-19-related anosmia: the olfactory pathway hypothesis and early intervention. Front Neurol. 2020;11:956–956. 10.3389/fneur.2020.00956. DOI: https://doi.org/10.3389/fneur.2020.00956
Froelich A, Osmałek T, Jadach B, Puri V, Michniak-Kohn B, et al. Microemulsion based media in nose-to-brain drug delivery. Pharmaceutics. 2021;13(2):201–201. 10.3390/pharmaceutics13020201. DOI: https://doi.org/10.3390/pharmaceutics13020201
Meltzer E, O E, Caballero F, M L, et al. Treatment of congestion in the upper respiratory diseases. Int J Gen Med. 2010;p. 69–91. 10.2147/IJGM.S8184. DOI: https://doi.org/10.2147/IJGM.S8184
Redzic Z. Molecular biology of the blood-brain and the blood-cerebrospinal fluid barriers: similarities and differences. Fluids and Barriers of the CNS. 2011;8(1):1–25. 10.1186/2045-8118-8-3. DOI: https://doi.org/10.1186/2045-8118-8-3
Vecchio I, Tornali C, Bragazzi NL, Martini M, et al. The discovery of insulin: an important milestone in the history of medicine. Front Endocrinol. 2018;9:613–613. 10.3389/fendo.2018.00613. DOI: https://doi.org/10.3389/fendo.2018.00613
Magkos F, Wang X, Mittendorfer B. Metabolic actions of insulin in men and women. Nutrition. 2010;26(7-8):686–693. 10.1016/j.nut.2009.10.013. DOI: https://doi.org/10.1016/j.nut.2009.10.013
Webber MJ, Kamat NP, Messersmith PB, Lecommandoux S, et al. Bioinspired macromolecular materials. Biomacromolecules. 2021;22(1):1–3. 10.1021/acs.biomac.0c01614. DOI: https://doi.org/10.1021/acs.biomac.0c01614
Bhat SS, Mukherjee D, Sukharamwala P, Dehuri R, Murali A, Teja BV, et al. Thiolated polymer nanocarrier reinforced with glycyrrhetinic acid for targeted delivery of 5- fluorouracil in hepatocellular carcinoma. Drug Deliv Transl Res. 2021;11(5):2252– DOI: https://doi.org/10.1007/s13346-020-00894-2
10.1007/s13346-020-00894-2. DOI: https://doi.org/10.1007/s13346-020-00894-2
Jun CS, Xu S, Ming WH. Nanoparticles: oral delivery for protein and peptide drugs. AAPS PharmSciTech. 2019;20(5):1–11. 10.1208/s12249-019-1325-z. DOI: https://doi.org/10.1208/s12249-019-1325-z
Singh AP, Biswas A, Shukla A, Maiti P, et al. Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles. Signal Transduct Target Ther. 2019;4(1):33–33. 10.1038/s41392-019-0068-3. DOI: https://doi.org/10.1038/s41392-019-0068-3
Chin J, Mahmud F, Kim KA, Park SE, Byun K, Y, et al. Insight of current technologies for oral delivery of proteins and peptides. Drug Discov Today Technol. 2012;9(2):105–112. 10.1016/j.ddtec.2012.04.005. DOI: https://doi.org/10.1016/j.ddtec.2012.04.005
Jana P, Shyam M, Singh S, Jayaprakash V, Dev A, et al. Biodegradable polymers in drug delivery and oral vaccination. Eur Polym J. 2021;142:110155–110155. 10.1016/j.eurpolymj.2020.110155. DOI: https://doi.org/10.1016/j.eurpolymj.2020.110155
Patra JK, Das G, Fraceto LF, et al. Nano based drug delivery systems: recent developments and future prospects. J anobiotechnology. 2018;16(1):71–71. 10.1186/s12951-018-0392-8. DOI: https://doi.org/10.1186/s12951-018-0392-8
Uner M, Yener G. Importance of solid lipid nanoparticles (SLN) in various administration routes and future perspectives. Int J Nanomedicine. 2007;2(3):289–300.
Dutta J. Isolation, Purification, and Nanotechnological Applications of Chitosan. Springer International Publishing; 2014. 10.1007/978-3-319-03751-645 − 1. DOI: https://doi.org/10.1007/978-3-319-03751-6_45-1
Sarmento B, Ribeiro A, Veiga F, et al. Alginate/Chitosan nanoparticles are effective for oral insulin delivery. Pharm Res. 2007;24(12):2198–2206. 10.1007/s11095-007- 9367-4. DOI: https://doi.org/10.1007/s11095-007-9367-4
Heidarisasan S, Ziamajidi N, Karimi J, Abbasalipourkabir R, et al. Effects of insulin loaded chitosan-alginate nanoparticle on RAGE expression and oxidative stress status in the kidney tissue of rats with type 1 diabetes. Iran J Basic Med Sci. 2018;21(10):1035–1042. 10.22038/ijbms.2018.28463.6899.
Stevanovic MM, Jordovic B, Uskokovic DP. Preparation and characterization of poly (D, L-lactide-co-glycolide) nanoparticles containing ascorbic acid. J biotechnol biomed. 2007;p. 1–8. 10.1155/2007/84965. DOI: https://doi.org/10.1155/2007/84965
Lombardo D, Kiselev MA, Caccamo MT. Smart nanoparticles for drug delivery application: development of versatile nanocarrier platforms in biotechnology and nanomedicine. J Nanomater. 2019;p. 1–26. 10.1155/2019/3702518. DOI: https://doi.org/10.1155/2019/3702518
Matteucci E, Giampietro O, Covolan V, Giustarini D, Fanti P, Rossi R, et al. Insulin administration: present strategies and future directions for a noninvasive (possibly more physiological) delivery. Drug Des Devel Ther. 2015;p. 3109–3109. 10.2147/DDDT.S79322. DOI: https://doi.org/10.2147/DDDT.S79322
Kaur S, Narayanan A, Dalvi S, Liu Q, Joy A, Dhinojwala A, et al. Direct observation of the interplay of catechol binding and polymer hydrophobicity in a mussel-inspired elastomeric adhesive. ACS Central Science. 2018;4(10):1420–1429. 10.1021/acscentsci. DOI: https://doi.org/10.1021/acscentsci.8b00526
b00526.
Sintov AC, Levy HV, Botner S. Systemic delivery of insulin via the nasal route using a new microemulsion system. J Control Release. 2010;148(2):168–176. 10.1016/j.jconrel.2010.08.004. DOI: https://doi.org/10.1016/j.jconrel.2010.08.004
Bailey TS, Stone JY. A novel pen-based Bluetooth-enabled insulin delivery system with insulin dose tracking and advice. Expert Opin Drug Deliv . 2017;14(5):697–703. 10.1080/17425247.2017.1313831. DOI: https://doi.org/10.1080/17425247.2017.1313831
Chen J, Hu L, Yang G, Hu Q, et al. Current therapeutic strategy in the nasal delivery of insulin: recent advances and future directions. Curr Pharm Biotechnol. 2018;19(5):400–415. 10.2174/1389201019666180619145429. DOI: https://doi.org/10.2174/1389201019666180619145429
Tashima T. Shortcut approaches to substance delivery into the brain based on intranasal administration using nanodelivery strategies for insulin. Molecules. 2020;25(21):5188–5188. 10.3390/molecules25215188. DOI: https://doi.org/10.3390/molecules25215188
Erdő F, Bors LA, Farkas D, Bajza A, Gizurarson S, et al. Evaluation of intranasal delivery route of drug administration for brain targeting. Brain Res Bull. 2018;143:155– 170. 10.1016/j.brainresbull.2018.10.009. DOI: https://doi.org/10.1016/j.brainresbull.2018.10.009
Crowe TP, Greenlee M, Kanthasamy AG, Hsu WH, et al. Mechanism of intranasal drug delivery directly to the brain. J Life Sci. 2018;195:44–52. 10.1016/j.lfs.2017.12.025. DOI: https://doi.org/10.1016/j.lfs.2017.12.025
Jeong SH, Jang JH, Lee YB. Drug delivery to the brain via the nasal route of administration: Exploration of key targets and major consideration factors. J Pharm Investig. 2023;53(1):119–152. 10.1007/s40005-022-00589-5. DOI: https://doi.org/10.1007/s40005-022-00589-5
Henkin RI. Intranasal insulin: From nose to brain. Nutrition. 2010;26(6):624–633. 10.1016/j.nut.2009.08.003. DOI: https://doi.org/10.1016/j.nut.2009.08.003
Stützle M, Flamm J, Carle S, Schindowski K, et al. Nose-to-Brain delivery of insulin for Alzheimer’s disease. ADMET DMPK. 2015;3(3):190–202. 10.5599/admet. 3.3.184. DOI: https://doi.org/10.5599/admet.3.3.184
Zhao WQ, Townsend M. Insulin resistance and amyloidogenesis as common molecular foundation for type 2 diabetes and Alzheimer’s disease. Biochim Biophys Acta Bioenerg . 2009;1792(5):482–496. 10.1016/j.bbadis.2008.10.014. DOI: https://doi.org/10.1016/j.bbadis.2008.10.014
Rasgon N, Jarvik GP, Jarvik L. Affective disorders and Alzheimer disease: a missing link hypothesis. Am J Geriatr Psychiatry. 2001;9(4):444–445. DOI: https://doi.org/10.1097/00019442-200111000-00015
Craft S, Baker LD, Montine TJ. Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial. Arch Neurol. 2012;69(1):29–38. 10.1001/archneurol.2011.233. DOI: https://doi.org/10.1001/archneurol.2011.233
Rasgon N, Jarvik L. Insulin Resistance, Affective Disorders, and Alzheimer’s Disease: Review and Hypothesis. J Gerontol - Biol Sci Med Sci. 2004;59(2):178–183. 10.1093/gerona/59.2.M178. DOI: https://doi.org/10.1093/gerona/59.2.M178
Steen E, Terry BM, Rivera J, E R, et al. Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer’s disease - is this type 3 diabetes? J Alzheimer’s Dis. 2005;7(1):63–80. 10.3233/JAD-2005-7107. DOI: https://doi.org/10.3233/JAD-2005-7107
Park HJ, Kim SK, Kang WS. Association between IRS1 Gene Polymorphism and Autism Spectrum Disorder: A Pilot Case-Control Study in Korean Males. Int J Mol Sci. 2016;17(8). 10.3390/ijms17081227. DOI: https://doi.org/10.3390/ijms17081227
Khalil B, R. Is insulin growth factor-1 the future for treating autism spectrum disorder and/or schizophrenia?; 2017. 10.1016/j.mehy.2016.12.004.
Additional Files
Published
Issue
Section
Categories
License
Copyright (c) 2023 Manoj Kumbhare, Ajaykumar R. Surana, Pravin G. Morankar

This work is licensed under a Creative Commons Attribution 4.0 International License.
The authors retain all proprietary rights, including copyright, such as patent and trademark rights and rights to any process or procedure described in the article.




