Development of novel formulations for mucosal delivery of protein ...

in the uptake of insulin into the systemic circulation (Modi, 2002). The administered INS
appears in the systemic circulation within 10 minutes of application. A maximum INS
bioavailability of 7-8 % was reached in about 30 minutes after application compared to 60
minutes when a subcutaneous INS injection was administered in a proof-of concept study
involving type 2 diabetic patients (Guevara-Aguirre, 2004). More clinical and toxicological
data is required to establish the efficacy of this system, however, Generex Oral-lyn, is
available for sale in Ecuador for the treatment of patients with Type-1 and Type-2 diabetes
and was approved for sale in India in October 2007. It is in various stages of clinical
development around the world as the global Phase III clinical trial of Generex Oral-lyn has
commenced in the USA, Canada, Russia, Ukraine, Romania, Bulgaria and Poland.
Figure 1.8: Buccal delivery of insulin from Generex Oral-lyn. Available at
[Accessed; 26/05/2011]
1.5.1 Pros and cons of protein delivery via the buccal mucosa
Among the major mucosal routes, the buccal mucosa has received increased attention
in recent years for the delivery of peptides as an alternative to currently used parenteral route
for protein delivery. Its advantages include the avoidance of pain (Antosova et al., 2009),
avoiding hepatic first-pass effect (Cornelius et al., 2005) and peptidase metabolism in the
gastrointestinal tract (Sudhakar et al., 2006).
Protein (peptide) absorption via the buccal mucosa is however, limited by drug
molecular size, hydrophobicity and low permeability of the mucosal membrane (Merkle &
Wolany, 1992) due to the relatively thick multi-layered buccal barrier and the high rate of
mucus turnover. An enzymatic barrier also exists at the mucosa which causes rapid
degradation of peptides and proteins, limiting their transport across the buccal mucosa. The
use of absorption enhancers, enzyme inhibitors and mucoadhesive systems which have been
investigated as strategies to improve absorption of protein drugs across the buccal mucosa
26