NANO ENABLED ORAL INSULIN DELIVERY SYSTEM FOR IMPROVED GASTROINTESTINAL ABSORPTION

Pavani Mandadi

Mandadi Pavani Priyadarshini Institute of Pharmaceutical Education and Research, 5th Mile, Pulladigunta, Guntur-522017, Andhra Pradesh, India.

Abstract

Oral delivery of insulin remains a long-standing challenge due to enzymatic degradation in the gastrointestinal tract, poor epithelial permeability, and rapid first-pass metabolism, resulting in extremely low bioavailability. Nano-enabled drug delivery systems have emerged as promising strategies to overcome these physiological barriers and improve patient compliance compared to subcutaneous injections. This review highlights recent advances in oral insulin nano-systems, including polymeric nanoparticles, liposomes, solid lipid nanoparticles, nano emulsions, micelles, dendrimers, and inorganic nanocarriers. These systems protect insulin from gastric degradation, enhance mucosal adhesion, facilitate transcellular or paracellular transport, and enable controlled release. Surface functionalization with targeting ligands, mucoadhesive polymers, and enzyme inhibitors further improves intestinal absorption and stability. Smart glucose-responsive nanocarriers capable of self-regulated insulin release are also gaining attention for achieving near-physiological glycemic control. Preclinical studies demonstrate improved pharmacokinetics, enhanced bioavailability, and significant hypoglycemic effects; though challenges related to large-scale manufacturing, long-term safety, and regulatory approval remain. Overall, oral insulin nano-delivery platforms represent a transformative approach toward non-invasive diabetes management, offering the potential for better therapeutic outcomes, improved patient adherence, and enhanced quality of life. Continued optimization and clinical translation are essential to realize their full potential in routine diabetes care.

Keywords: Oral insulin, Nanotechnology, Nano drug delivery systems, Polymeric nanoparticles, Solid lipid nanoparticles

Downloads

Download data is not yet available.

References

1. Chandu BR, Nama S, Kanala K, Challa BR, Shaik RP, Khagga M. Quantitative estimation of riluzole in human plasma by LC-ESI-MS/MS and its application to a bioequivalence study. Anal Bioanal Chem. 2010;398(3):1367-1374.
2. Kiranmai M, Renuka P, Brahmaiah B, Chandu BR. Vitamin D as a promising anticancer agent. Int J Adv Clin Med. 2012.
3. Rao AA, Rao CB, Devanna N. Design and evaluation of mucoadhesive buccal bilayered tablets of metoprolol succinate. World J Pharm Res. 2017;7(3):172-178.
4. Degapati RT. Novel approaches in transdermal drug delivery system. J Multidiscip Res. 2025:20-25.
5. Rao C. Evaluation of antiulcer activity of Picrasma quassioides Bennett aqueous extract in rodents. Vedic Res Int Phytomedicine. 2013.
6. Gindi S, Methra T, Chandu BR, Boyina R, Dasari V. Antiurolithiatic and in vitro antioxidant activity of leaves of Ageratum conyzoides in rats. World J Pharm Pharm Sci. 2013;2(2):636-649.
7. Liu L, Zhang Y, Yu S, Zhang Z, He C, Chen X. pH- and amylase-responsive carboxymethyl starch/poly(2-isobutyl-acrylic acid) hybrid microgels as effective enteric carriers for oral insulin delivery. Biomacromolecules. 2018;19(6):2123-2136.
8. Liu C, Xu H, Sun Y, Zhang X, Cheng H, Mao S. Design of virus-mimicking polyelectrolyte complexes for enhanced oral insulin delivery. J Pharm Sci. 2019;108(10):3408-3415.
9. Daugherty AL, Mrsny RJ. Transcellular uptake mechanisms of the intestinal epithelial barrier. Part one. Pharm Sci Technol Today. 1999;2(4):144-151.
10. Panigrahy SK, Kumar A. Biopolymeric nanocarrier: an auspicious system for oral delivery of insulin. J Biomater Sci Polym Ed. 2022;33(16):2145-2164.
11. Zaiki Y, Lim LY, Wong TW. Critical material designs for mucus- and mucosa-penetrating oral insulin nanoparticle development. Int Mater Rev. 2023;68(2):121-139.
12. Shahzadi I, Fürst A, Knoll P, Bernkop-Schnürch A. Nanostructured lipid carriers (NLCs) for oral peptide drug delivery: about the impact of surface decoration. Pharmaceutics. 2021;13(8):1312.
13. Esrafili A, Wagner A, Inamdar S, Acharya AP. Covalent organic frameworks for biomedical applications. Adv Healthc Mater. 2021;10(6):2002090.
14. Reddy CC, Khilji IA, Gupta A, Bhuyar P, Mahmood S, Al-Japairai KA, Chua GK. Valorization of keratin waste biomass and its potential applications. J Water Process Eng. 2021;40:101707.
15. Juère E, Caillard R, Marko D, Del Favero G, Kleitz F. Smart protein-based formulation of dendritic mesoporous silica nanoparticles: toward oral delivery of insulin. Chem Eur J. 2020;26(23):5195-5199.
16. Fu HR, Wang N, Qin JH, Han ML, Ma LF, Wang F. Spatial confinement of a cationic MOF: a SC-SC approach for high-capacity Cr(VI)-oxyanion capture in aqueous solution. Chem Commun (Camb). 2018;54(82):11645-11648.
17. Farokhzad OC, Langer R. Impact of nanotechnology on drug delivery. ACS Nano. 2009;3(1):16-20.
18. Kecman S, Škrbić R, Badnjevic Cengic A, Mooranian A, Al-Salami H, Mikov M, Golocorbin-Kon S. Potentials of human bile acids and their salts in pharmaceutical nano delivery and formulation adjuvants. Technol Health Care. 2020;28(3):325-335.
19. Ren S, Wang C, Guo L, Xu C, Wang Y, Sun C, Cui H, Zhao X. Preparation and sustained-release performance of PLGA microcapsule carrier system. Nanomaterials (Basel). 2021;11(7):1758.
20. Yeh TH, Hsu LW, Tseng MT, Lee PL, Sonaje K, Ho YC, Sung HW. Mechanism and consequence of chitosan-mediated reversible epithelial tight junction opening. Biomaterials. 2011;32(26):6164-6173.
21. Thanou M, Verhoef JC, Marbach P, Junginger HE. Intestinal absorption of octreotide: N-trimethyl chitosan chloride (TMC) ameliorates the permeability and absorption properties of the somatostatin analogue in vitro and in vivo. J Pharm Sci. 2000;89(7):951-957.
22. Bloomgarden Z. Novel approaches to the treatment of type 1 diabetes. J Diabetes. 2022;14(11):724.