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l-Valine appended PLGA nanoparticles for oral insulin delivery

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Abstract

Aims

Oral insulin delivery has been the major research issue, since many decades, due to several obvious advantages over other routes. However, this route poses several constraints for the delivery of peptides and proteins which are to be worked upon. The small intestine has been shown to be able to transport the l-forms of amino acids against a concentration gradient and that they compete for the mechanism concerned. So, l-valine was used as a ligand for carrier-mediated transport of insulin-loaded polylactic-co-glycolic acid (PLGA) nanoparticles (NPs).

Methods

l-Valine-conjugated PLGA nanoparticles were prepared using double emulsion solvent evaporation method. The NPs and conjugated NPs were characterized for their size, drug entrapment efficiency, zeta potential, polydispersity index and in vitro insulin release.

Results

Ex vivo studies on intestine revealed that conjugated nanoparticles showed greater insulin uptake as compared to non-conjugated nanoparticles. In vivo studies were performed on streptozotocin-induced diabetic rabbits. Oral suspension of insulin-loaded PLGA nanoparticles reduced blood glucose level from 265.4 ± 8.5 to 246.6 ± 2.4 mg/dL within 4 h which further decreased to 198.7 ± 7.1 mg/dL value after 8 h. The ligand-conjugated formulation on oral administration produced hypoglycaemic effect (216.9 ± 1.9 mg/dL) within 4 h of administration, and the hypoglycaemic effect prolonged till 12 h of oral administration. Simultaneously, the insulin concentration in withdrawn samples was also assessed and found that profile of insulin level is in compliance with the blood glucose reduction profile.

Conclusions

Hence, it is concluded that the l-valine-conjugated NPs bearing insulin are the promising carrier for the transportation of insulin across the intestine on oral administration.

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Acknowledgments

The authors are thankful to Biocon, Bengaluru, India, for generously providing gift sample of insulin, Sun Pharmaceuticals Advanced Research Center (SPARC), Baroda, India, for providing PLGA (50:50) and Council of scientific and industrial Research, New Delhi, for financial assistance (RA).

Conflict of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Ethical standard

This article does not contain any studies with human participants or animals performed by any of the authors.

Human and animal rights disclosure

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008.

Informed consent disclosure

No human studies were carried out in this article.

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Authors and Affiliations

  1. Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour Vishwavidyalaya, Sagar, 470 003, M.P., India

    Ashish Jain & Sanjay K. Jain

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  1. Ashish Jain
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  2. Sanjay K. Jain
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Correspondence to Sanjay K. Jain.

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Jain, A., Jain, S.K. l-Valine appended PLGA nanoparticles for oral insulin delivery. Acta Diabetol 52, 663–676 (2015). https://doi.org/10.1007/s00592-015-0714-3

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  • DOI: https://doi.org/10.1007/s00592-015-0714-3

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