Abstract
Our study investigates the effect of magnetosome mediated oral Insulin delivery on diabetic induced rat models. The study involves the development of Magnetosome-Insulin (MI) conjugates by direct and indirect (by means of PEG) coupling method and further characterized by microscopic and spectroscopic analysis. The in vivo oral delivery of magnetosome-Insulin conjugate against streptozotocin-induced rat models and its efficiency was investigated. The impact of MI showed a remarkable change in the reduction of FBG levels up to 65% than the standard (Insulin). Similarly, the serum parameters: triglycerides (43.81%), AST&ALT (39.4 and 57.2%), total cholesterol (43.8%) showed significant changes compared to the diabetic control. The histological results of MI treated rats were found similar to control rats. Thus, these significantly notable results on diabetic rats depicts that magnetosomes can be employed as a potential approach and a very promising alternative for the parenteral route of Insulin delivery.
Similar content being viewed by others
Abbreviations
- MTB:
-
Magnetotactic bacteria
- DSMZ:
-
Deutsche Sammlung von Mikroorganismen und Zellkulturen
- MSGM:
-
Magnetospirillum growth medium
- FTIR:
-
Fourier-transform infrared spectroscopy
- HRTEM:
-
High resolution transmission electron microscopy
- XRD:
-
X-ray diffraction
- HPLC:
-
High pressure liquid chromatography
- FBG:
-
Fast blood glucose
- STZ:
-
Streptozotocin
- PEG:
-
Polyethylene glycol
- MI:
-
Insulin magnetosome conjugate
- MPI:
-
Insulin Magnetosome conjugate via PEG
- I:
-
Insulin (Standard drug)
References
Elena M, Matoori S, Leroux J-C. Oral delivery of macromolecular drugs: where we are after almost 100 years of attempts. Adv Drug Deliv Rev. 2016;101:108–21.
Pérez YA, Urista CM, Martínez JI, Nava MDCD, Rodríguez FAR. Functionalized polymers for enhance oral bioavailability of sensitive molecules. Polymers. 2016;8(6):214.
Abdul M. et al. A review on the strategies for oral delivery of proteins and peptides and their clinical perspectives. Saudi Pharm J. 2016;24.4:413–28.
Ana B. et al. Nanostructured lipid carriers: Promising drug delivery systems for future clinics. Nanomedicine. 2016;12.1:43–161.
Parveen S, Misra R, Sahoo SK. Nanoparticles: a boon to drug delivery, therapeutics, diagnostics and imaging. Nanomedicine: Nanotechnol Biol Med. 2012;8(2):147–66.
Ashaben P. et al. Recent advances in protein and peptide drug delivery: a special emphasis on polymeric nanoparticles. Protein Pept Lett. 2014;21.11:1102–20.
Ahmed TA, Aljaeid BM. Preparation, characterization, and potential application of chitosan, chitosan derivatives, and chitosan metal nanoparticles in pha rmaceutical drug delivery. Drug Des Devel Ther. 2016;10:483.
Faraji AH, Wipf P. Nanoparticles in cellular drug delivery. Bioorg Med Chem. 2009;17(8):2950–62.
Montanari Stefano, Antonietta Gatti M. Nanopathology: the health impact of nanoparticles. CRC Press, Boca Raton, Florida, USA; 2016.
Almeida AJ, Souto E. Solid lipid nanoparticles as a drug delivery system for peptides and proteins. Adv. Drug Deliv Rev. 2007;59.6:478–90.
Elçioğlu HK, Sezer AD. Nanoparticle insulin drug delivery—applications and new aspects. Appl Nanotechnol Drug Deliv. 2014;4:237.
Sharma G. et al. Nanoparticle based Insulin delivery system: the next generation efficient therapy for Type 1 diabetes. J Nanobiotechnol. 2015;13.1:74
Alejandro S, Augustine R. Challenges in oral drug delivery of antiretrovirals and the innovative strategies to overcome them. Adv Drug Deliv Rev. 2016;103:105–20.
Yun Y, Cho WY, Park K. Nanoparticles for oral delivery: targeted nanoparticles with peptidic ligands for oral protein delivery. Adv Drug Deliv Rev. 2013;65:822–32.
Hua S. et al. Advances in oral nano-delivery systems for colon targeted drug delivery in inflammatory bowel disease: selective targeting to diseased versus healthy tissue. Nanomed Nanotechnol. 2015;11.5:1117–32.
Jacob JJ, Suthindhiran K. Magnetotactic bacteria and magnetosomes—scope and challenges. Mater Sci Eng C Mater. 2016;68:919–28.
Dasdag S, Bektas H. Magnetotactic bacteria and their application in medicine. J Phys Chem Biophys. 2014;2(4):2161–0398.
Raguraman, V, Suthindhiran K, Comparative ecotoxicity assessment of magnetosomes and magnetite nanoparticles, Int J Environ Health Res. 2019:1–13.
Hungate, RE. Chapter IV A roll tube method for cultivation of strict anaerobes. Methods Microbiol. 1969;3:117–32.
Berry CC, Adam SGC. Functionalisation of magnetic nanoparticles for applications in biomedicine. J Phys D: Appl Phys. 2003;36.13:R198.
**ang L. et al. Purified and sterilized magnetosomes from Magnetospirillum gryphiswaldense MSR‐1 were not toxic to mouse fibroblasts in vitro. Lett Appl Microbiol. 2007;45.1:75–81.
Frankel RB, Blakemore RP, Wolfe RS. Magnetite in freshwater magnetotactic bacteria. Science. 1979;203.4387:1355–6.
Revathy T, Jayasri MA, Suthindhiran K. Toxicity assessment of magnetosomes in different models. 3 Biotech. 2017;7.2:126.
Bhumkar DR, Joshi HM, Sastry M, Pokharkar VB. Chitosan reduced gold nanoparticles as novel carriers for transmucosal delivery of Insulin. Pharm. Res. 2007;24(8):1415–26.
Andreani T. et al. Preparation and characterization of PEG-coated silica nanoparticles for oral Insulin delivery. Int J Pharm. 2014;473.1-2:627–35.
Piyasi M. et al. pH-sensitive chitosan/alginate core-shell nanoparticles for efficient and safe oral Insulin delivery. Int J Biol Macromol. 2015;72:640–8.
Unnikrishnan PS, Jayasri MA. Antidiabetic studies of Chaetomorpha antennina extract using experimental models. J Appl Psychol. 2017;29.2:1047–56.
Hinds KD, Kim SW. Effects of PEG conjugation on Insulin properties. Adv Drug Deliv Rev. 2002;54:505–30.
Marlene L. et al. Dual chitosan/albumin-coated alginate/dextran sulfate nanoparticles for enhanced oral delivery of Insulin. J Control Release. 2016;232:29–41.
Pedro F. et al. Polymer-based nanoparticles for oral Insulin delivery: revisited approaches. Biotechnol Adv. 2015;33.6:1342–54.
Meredith HL, Lowman AM. Biodegradable nanoparticles for drug delivery and targeting. Curr Opin Solid State Mater Sci. 2002;6:319–27.
Chen M-C. et al. A review of the prospects for polymeric nanoparticle platforms in oral Insulin delivery. Biomaterials. 2011;32:9826–38.
Moussa BA, Farouk F, Azzazy HME. A validated RP-HPLC method for the determination of recombinant human Insulin in bulk and pharmaceutical dosage form. J Chem. 2010;7(S1):S449–57.
Singh MA. Magnetotactic bacteria: nanodrivers of the future. Crit Rev Biotechnol. 2016;36.5:788–802.
**g X, Li A, Li J. Advances in pH‐sensitive polymers for smart insulin delivery. Macromol Rapid Commun. 2017;38.23:1700413.
Rinku DU, Paknikar KM. Zinc oxide nanoparticles show antidiabetic activity in streptozotocin-induced Type 1 and 2 diabetic rats. Nanomedicine. 2014;9.1:89–104.
Naskar S, Sharma S, Koutsu K. Chitosan-based nanoparticles: an overview of biomedical applications and its preparation. J Drug Deliv Sci Technol. 2019;49:66–81.
Acknowledgements
This work was supported by VIT University. The authors thank the management for providing the facilities for the research.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Raguraman, V., Jayasri, M.A. & Suthindhiran, K. Magnetosome mediated oral Insulin delivery and its possible use in diabetes management. J Mater Sci: Mater Med 31, 75 (2020). https://doi.org/10.1007/s10856-020-06417-2
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s10856-020-06417-2