Proteomics - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 388

to current retroviral therapy. Despite extensive research for the last two decades,
there has been a dearth of potential biomarkers for diagnosis of these complications.
Development in the identification of proteomic biomarkers, profiling, resolution, and
analysis has been relatively slow. Wiederin et al. [3] investigated some serum-based
proteomic biomarkers for HIV-associated dementia disorders. The conclusions drawn
from this work stressed the importance of multiple protein profiling approaches and
multiple sample fractionation schemes to assess changes in proteomes due to patho-
logical conditions.
8.2 Changing Requirements of Proteins and Peptides
Delivery
Many peptides and proteins have been commercially explored since the 1950s. Initial
explorations were for peptide-based hormonal drugs and analogs. The commencement
and completion of the human genome project is considered an important landmark in
areas of protein research because more than 84% of total human proteins have been
sequenced and their structures predicted. However, the development of proteins and
peptide molecules as drug candidates has taken place at only a snail's pace because
of various technical constraints. Proteins and peptide markets are of immense poten-
tial because many vaccines and similar derivatives are predominantly protein or pep-
tide based. Major limitations of proteins and peptides are the lack of knowledge of the
effects of the administration route and the physicochemical properties of proteins that
influence their pharmacokinetics and in vivo behavioral profile. Most proteins are
delivered by parenteral routes that are invasive in nature, for example, insulin by sub-
cutaneous route. The thermolabile nature, high molecular weight, solubility, stability,
intestinal permeability, tendency to undergo complexation, and susceptibility to pro-
teolytic enzymes in the gastrointestinal tract upon oral administration of proteins are
other key factors that constraint the use of proteins in delivery. However, drug delivery
systems by various routes of administration like buccal, nasal, vaginal, and transdermal
(iontophoresis and similar techniques) have been tried.
The utility of proteins and their immense potential as drug candidates motivate
pharmaceutical scientists to develop suitable and commercially feasible drug delivery
systems. This is evident from the fact that more than 40% of pharmaceutical compa-
nies are actively working in this area. The consolidation of molecular biology, bio-
technology, and pharmaceutical sciences is seen as a major hope in this direction.
8.2.1 Use of Penetration Enhancers
Penetration enhancers have been tried for enhancing transmucosal peptide transport.
However, they have been of little utility in dermal delivery of peptides due to the
presence of keratinized barrier in stratum corneum that acts as a rate-limiting bar-
rier for protein drug delivery. Surfactants like sodium lauryl sulfate (SLS) and others
have been found to be valuable for in vivo transdermal drug delivery of molecules