Development and Evaluation of PEG-gelatin-based Microparticles to Enhance the Oral Delivery of Insulin

  • Authors: Buxaderas E.1, Akpa P.2, Hanifah A.3, Oseni O.4, Kenechukwu F.2, Mumuni M.5, Diaz D.6, Alfa J.7, Ben A.8
  • Affiliations:
    1. Instituto Universitario de Bio-Orgánica Antonio González, Instituto Universitario de Bio-Orgánica Antonio González
    2. Drug Delivery Research Unit, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Nigeria
    3. Department of Medical Laboratory Sciences,, Usmanu Danfodiyo University Sokoto
    4. Department of Microbiology, Faculty of Natural Sciences, Kogi State University,
    5. Drug Delivery Research Unit, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences,, University of Nigeria
    6. , Instituto Universitario de Bio-Orgánica Antonio González,
    7. Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Bingham University
    8. Department of Pharmaceutical Technology and Industrial Pharmacy, Faculty of Pharmaceutical Sciences,, University of Nigeria
  • Issue: Vol 30, No 24 (2024)
  • Pages: 1939-1948
  • Section: Immunology, Inflammation & Allergy
  • URL: https://vestnikugrasu.org/1381-6128/article/view/645833
  • DOI: https://doi.org/10.2174/0113816128309449240527053640
  • ID: 645833

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Abstract

Background:Diabetes mellitus is a global disease identified by hyperglycemia due to defects in insulin secretion, insulin action, or both.

Objective:The main objective of this research was to evaluate the ability of gelatinized Poly(ethylene glycol) (PEG) microparticles to be used as carriers for oral insulin delivery via double emulsion preparation.

Methods:Five different batches of the formulation consisting of gelatin:PEG were prepared as follows: 0:1 (W1), 1:0 (W2), 1:1 (W3), 1:3 (W4), and 3:1 (W5). The prepared microparticles (from insulin-loaded batches) had particle sizes ranging from 19.5 ± 0.32-23.9 ± 0.22 µm and encapsulation and loading capacities ranging from 78.8 ± 0.24-88.9 ± 0.95 and 22.2 ± 0.96-29.7 ± 0.86%, respectively. The minimum and maximum in vitro release rates were 8.0 and 66.0%, respectively, for batches W1 and W2 at 8 h.

Results:Insulin-loaded MPs induced a significant decrease in glucose levels, with a reduction from 100 to 33.35% in batch W5 at 9 h compared to that of subcutaneous insulin (100 to 22.63%). A liver function study showed that the formulation caused no obvious toxicity to the experimental rats.

Conclusion:Gelatinized PEG-based microparticles as insulin delivery systems may open a new window into the development of oral insulin for diabetic treatment.

About the authors

Eduardo Buxaderas

Instituto Universitario de Bio-Orgánica Antonio González, Instituto Universitario de Bio-Orgánica Antonio González

Email: info@benthamscience.net

Paul Akpa

Drug Delivery Research Unit, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Nigeria

Email: info@benthamscience.net

Abdulmumin Hanifah

Department of Medical Laboratory Sciences,, Usmanu Danfodiyo University Sokoto

Email: info@benthamscience.net

Okolo Oseni

Department of Microbiology, Faculty of Natural Sciences, Kogi State University,

Email: info@benthamscience.net

Franklin Kenechukwu

Drug Delivery Research Unit, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Nigeria

Email: info@benthamscience.net

Momoh Mumuni

Drug Delivery Research Unit, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences,, University of Nigeria

Author for correspondence.
Email: info@benthamscience.net

David Diaz

, Instituto Universitario de Bio-Orgánica Antonio González,

Author for correspondence.
Email: info@benthamscience.net

John Alfa

Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Bingham University

Email: info@benthamscience.net

Amadi Ben

Department of Pharmaceutical Technology and Industrial Pharmacy, Faculty of Pharmaceutical Sciences,, University of Nigeria

Email: info@benthamscience.net

References

  1. Hong J, Surapaneni A, Daya N, et al. Retinopathy and risk of kidney disease in persons with diabetes. Kidney Med 2021; 3(5): 808-815.e1. doi: 10.1016/j.xkme.2021.04.018 PMID: 34693260
  2. Zimmet PZ. Diabetes and its drivers: The largest epidemic in human history? Clin Diabetes Endocrinol 2017; 3(1): 1. doi: 10.1186/s40842-016-0039-3 PMID: 28702255
  3. Misra A, Gopalan H, Jayawardena R, et al. Diabetes in developing countries. J Diabetes 2019; 11(7): 522-39. doi: 10.1111/1753-0407.12913 PMID: 30864190
  4. a) Todd JA. Etiology of type 1 diabetes. Immunity 2010; 32(4): 457-67. doi: 10.1016/j.immuni.2010.04.001 PMID: 20412756; b) Bluestone JA, Herold K, Eisenbarth G. Genetics, pathogenesis and clinical interventions in type 1 diabetes. Nature 2010; 464(7293): 1293-300. doi: 10.1038/nature08933 PMID: 20432533
  5. DeFronzo RA, Ferrannini E, Groop L, et al. Type 2 diabetes mellitus. Nat Rev Dis Primers 2015; 1(1): 15019. doi: 10.1038/nrdp.2015.19 PMID: 27189025
  6. Roham PH, Save SN, Sharma S. Human islet amyloid polypeptide: A therapeutic target for the management of type 2 diabetes mellitus. J Pharm Anal 2022; 12(4): 556-69. doi: 10.1016/j.jpha.2022.04.001 PMID: 36105173
  7. Frokjaer S, Otzen DE. Protein drug stability: A formulation challenge. Nat Rev Drug Discov 2005; 4(4): 298-306. doi: 10.1038/nrd1695 PMID: 15803194
  8. Meneguin AB, Silvestre ALP, Sposito L, et al. The role of polysaccharides from natural resources to design oral insulin micro and nanoparticles intended for the treatment of Diabetes mellitus: A review. Carbohydr Polym 2021; 256: 117504. doi: 10.1016/j.carbpol.2020.117504 PMID: 33483027
  9. Drucker DJ. Advances in oral peptide therapeutics. Nat Rev Drug Discov 2020; 19(4): 277-89. doi: 10.1038/s41573-019-0053-0 PMID: 31848464
  10. Ji K, Yao Y, Wei X, et al. Material design for oral insulin delivery. Med-X 2023; 1(1): 7. doi: 10.1007/s44258-023-00006-y PMID: 37485249
  11. Krauland AH, Guggi D, Bernkop-Schnürch A. Oral insulin delivery: The potential of thiolated chitosan-insulin tablets on non-diabetic rats. J Control Release 2004; 95(3): 547-55. doi: 10.1016/j.jconrel.2003.12.017 PMID: 15023465
  12. Ofokansi K, Winter G, Fricker G, Coester C. Matrix-loaded biodegradable gelatin nanoparticles as new approach to improve drug loading and delivery. Eur J Pharm Biopharm 2010; 76(1): 1-9. doi: 10.1016/j.ejpb.2010.04.008 PMID: 20420904
  13. Momoh MA, Emmanuel OC, Onyeto AC, et al. Preparation of snail cyst and PEG-4000 composite carriers via PEGylation for oral delivery of insulin: An in vitro and in vivo evaluation. Trop J Pharm Res 2021; 18(5): 919-26. doi: 10.4314/tjpr.v18i5.2
  14. Momoh MA, Adedokun MO, Adikwu MU, Kenechukwu FC, Ibezim EC, Ugwoke EE. Design, characterization and evaluation of PEGylated-mucin for oral delivery of metformin hydrochloride. Afr J Pharm Pharmacol 2013; 7(7): 347-55. doi: 10.5897/AJPP12.488
  15. Mumuni MA, Kenechukwu FC, Ernest OC, et al. Surface-modified mucoadhesive microparticles as a controlled release system for oral delivery of insulin. Heliyon 2019; 5(9): e02366. doi: 10.1016/j.heliyon.2019.e02366 PMID: 31535040
  16. Kenechukwu FC, Attama AA, Ibezim EC, et al. Surface-modified mucoadhesive microgels as a controlled release system for miconazole nitrate to improve localized treatment of vulvovaginal candidiasis. Eur J Pharm Sci 2018; 111: 358-75. doi: 10.1016/j.ejps.2017.10.002 PMID: 28986195
  17. Erel G, Kotmakçı M, Akbaba H, Sözer Karadağlı S, Kantarcı AG. Nanoencapsulated chitosan nanoparticles in emulsion-based oral delivery system: In vitro and in vivo evaluation of insulin loaded formulation. J Drug Deliv Sci Technol 2016; 36: 161-7. doi: 10.1016/j.jddst.2016.10.010
  18. Ma Z, Lim TM, Lim LY. Pharmacological activity of peroral chitosan–insulin nanoparticles in diabetic rats. Int J Pharm 2005; 293(1-2): 271-80. doi: 10.1016/j.ijpharm.2004.12.025 PMID: 15778065
  19. Simon-Giavarotti KA, Giavarotti L, Gomes LF, et al. Enhancement of lindane-induced liver oxidative stress and hepatotoxicity by thyroid hormone is reduced by gadolinium chloride. Free Radic Res 2002; 36(10): 1033-9. doi: 10.1080/1071576021000028280 PMID: 12516873
  20. Kasarala G, Tillmann HL. Standard liver tests. Clin Liver Dis 2016; 8(1): 13-8. doi: 10.1002/cld.562 PMID: 31041056
  21. Rosas PC, Nagaraja GM, Kaur P, et al. Hsp72 (HSPA1A) prevents human islet amyloid polypeptide aggregation and toxicity: A new approach for type 2 diabetes treatment. PLoS One 2016; 11(3): e0149409. doi: 10.1371/journal.pone.0149409 PMID: 26960140
  22. Ibraheem D, Elaissari A, Fessi H. Administration strategies for proteins and peptides. Int J Pharm 2014; 477(1-2): 578-89. doi: 10.1016/j.ijpharm.2014.10.059 PMID: 25445533

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