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: Novel Approaches for Oral Delivery of Insulin and Current Status of Oral Insulin Products 1057
International Journal of Pharmaceutical Sciences and Nanotechnology
Volume 3 Issue 3 October - December 2010
Review Article
Novel Approaches for Oral Delivery of Insulin and Current Status of
Oral Insulin Products
Kinesh V. P.*, Neelam D. P., Punit. B. P., Bhavesh S.B., Pragna K. S.
Department of Pharmaceutics and Pharmaceutical Technology
K. B. Institute of Pharmaceutical Education & Research, Gandhinagar-India
ABSTRACT:
Diabetes mellitus is a serious pathologic condition that is responsible for major healthcare problems
worldwide and costing billions of dollars annually. Insulin replacement therapy has been used in the clinical management of
diabetes mellitus for more than 84 years. The present mode of insulin administration is by the subcutaneous route through
which insulin is presented to the body in a non-physiological manner having many challenges. Hence novel approaches for
insulin delivery are being explored. Challenges to oral route of insulin administration are: rapid enzymatic degradation in the
stomach, inactivation and digestion by proteolytic enzymes in the intestinal lumen and poor permeability across intestinal
epithelium because of its high molecular weight and lack of lipophilicity. Liposomes, microemulsions, nanocubicles, and so
forth have been prepared for the oral delivery of insulin. Chitosan-coated microparticles protected insulin from the gastric
environment of the body and released intestinal pH. Limitations to the delivery of insulin have not resulted in fruitful results
to date and there is still a need to prepare newer delivery systems, which can produce dose-dependent and reproducible
effects, in addition to increased bioavailability.
cannot diffuse across epithelial cells through lipidbilayer cell membranes to the blood stream (Lin YH
et al., 2007). In other words, insulin has low
permeability through the intestinal mucosa (Torisaka
E et al., 2005). There is no evidence of active
transport for insulin (Schilling RJ et al., 1999). It has
been found however that insulin delivery to the midjejunum protects insulin from gastric and pancreatic
enzymes and release from the dosage form is
enhanced by intestinal microflora (Schilling RJ et al.,
1999; Koosapur H et al., 1999). Various strategies
have been tried out to enhance the absorption of
insulin in the intestinal mucosa and in some cases;
they have proven successful in overcoming this
barrier.
Enzymatic Barrier
The harsh environment of the gastrointestinal tract
(GIT) causes insulin to undergo degradation. This is
because digestive processes are designed to
breakdown proteins and peptides without any
discrimination. (Tuesca A et al., 2006) Insulin
therefore undergoes enzymatic degradation by pepsin
and pancreatic proteolytic enzymes such as trypsin
and -chymotrypsin (Agarwal V et al., 2001; Patki
VP et al., 1996). Overall, insulin is subjected to acidcatalyzed degradation in the stomach, luminal
degradation in the intestine and intracellular
degradation. The cytosolic enzyme that degrades
insulin is insulin-degrading enzyme (IDE) (Chang LL
et al., 1999).Insulin is however not subject to
proteolytic breakdown by brush border enzymes
(Agarwal V et al., 2001). Insulin can be presented for
absorption only if the enzyme attack is either reduced
or defeated.
Intestinal Transport of Insulin
Another major barrier to the absorption of
hydrophilic macromolecules like insulin is that they
Kinesh V.P. et.al. : Novel Approaches for Oral Delivery of Insulin and Current Status of Oral Insulin Products 1059
Kinesh V.P. et.al. : Novel Approaches for Oral Delivery of Insulin and Current Status of Oral Insulin Products 1061
Oral spray
Conclusion
Attempts have been made to achieve oral insulin
delivery using various systems. It has been proved
that insulin is subjected to acid catalyzed degradation
in stomach, luminal degradation in intestine, and
intracellular degradation. Scientists have been able to
protect the insulin delivery systems from acidic
environment of the stomach and target it to the
intestine. The maximum bioavailability of the insulin
has been reported to be very low because of the poor
absorption of insulin from the intestine. Attempts
have been made to increase the absorption of insulin
from intestine using absorption enhancers such as
aprotinin (protease inhibitor), tween, oligoarginine,
sodium glycol-cholate, deoxycholic acid, and
taurodeoxycholate.
Liposomes, microemulsions, nanocubicles, etc.,
have been prepared for the oral delivery of insulin.
Chitosan-coated microparticles protected insulin from
the gastric environment of the body and released it in
intestinal pH. Limitations to the delivery of insulin
have not resulted in fruitful results to date and there is
still a need to prepare newer delivery systems, which
can produce dose-dependent and reproducible effects
in addition to increased bioavailability.
References
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Agarwal V, Reddy IK, Khan MA. Polyethylacrylate-based
microparticulate of insulin for oral delivery: preparation and
in vitro dissolution stability in the presence of enzyme
inhibitors. Int. J Pharm.; 225 (12), 3139 (2001).
Ahmed I, Goldstein B. Diabetes Mellitus, Clin. Dermatol. 24 (4),
237246 (2006).
Kinesh V.P. et.al. : Novel Approaches for Oral Delivery of Insulin and Current Status of Oral Insulin Products 1063
Kumar A, Lahiri SS, Singh H. Development of PEGDMA: MAA
based hydrogel Microparticles for oral insulin delivery. Int. J.
Pharm. 12: 323(1-2):117-24 (2006).