Design of Insulin Variants for Improved Treatment of Diabetes - Peptide and Protein Design for Biopharmaceutical Applications - page 269

Inflammation will rather quickly initiate at the site of foreign-object
insertion [147], and the current sensors must only be used for three
days. They must furthermore be calibrated against two to three daily
finger pricks.
Many scientists have attempted to develop non-invasive blood glucose
monitoring by using infrared spectroscopy, among other things, but so
far with limited success [148]. Glucose is difficult to detect and distin-
guish from other substances in the human tissue. Semi-invasive methods
like glucose monitoring using contact lenses or optic fibres are under
investigation [149,150].

7.8 ALTERNATIVE INSULIN DELIVERY

Injection is not the most convenient form of drug administration and
many people think that insulin injections are painful, although this is
not true with modern needles, as discussed previously. Against this
background, scientists have investigated alternative administration
forms including various engineerings of the insulin molecule for better
stability of insulin in proteolytic environments or for better uptake
through biological barriers. Oral delivery of native insulin leads to
very low bioavailability due to degradation in the gut by acid and by
proteases, and due to the generally very low gut absorption of large
molecules [151].
Insulin PEGylation (derivatization of insulin with functionalized poly-
ethylenglycol) has been claimed to provide better oral uptake of insulin,
and Nobex/Biocon currently conduct oral clinical trials of insulin deri-
vatized by short-chain alkyl-PEGylation [152]. Despite improvements
over native insulin, bioavailability is still very low. Furthermore, the
influence on insulin absorption of different stomach content from day
to day will make predictable and reliable dosing of oral insulin a signifi-
cant problem.
Pfizer launched pulmonary insulin, Exubera [153], in 2006, based on
an insulin powder inhaler. The bioavailability of Exubera is low (10%),
but this issue could be adjusted via dosing, and glucose control compar-
able to that of injectable insulin can be reached with pulmonary insulin
[154]. Notably, Exubera is based on human insulin, which does not
provide basal coverage, so basal insulins must be added via injections.