Proteomics - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 420

there exists a linear relationship between the lymphatic absorption profile and the
molecular weight of a protein. Predominant lymphatic absorption of high-molecular-
weight proteins render them suitable for therapeutic use in lymph disorders and
lymphoid syndromes.
8.8.2 Inhalational Administration of Proteins
The inhalational route for pulmonary delivery of proteins has attracted a great deal
of scientific attention. Availability of a comparatively larger surface area for absorp-
tion, high vascularization, avoidance of first-pass metabolism, noninvasiveness, and
the benefits of local delivery make this route of administration extremely fascinating.
However, the presence of proteolytic enzymes in the lungs, local side effects of the
administered protein, high molecular weight, constraints in particle size, and aerody-
namic properties of the drug candidate are major obstacles to be overcome. Scientists
have developed inhalable insulin that offers quicker onset of action with the added
advantage of noninvasiveness and ease of administration supplemented with better
control on postprandial glucose levels in the blood as compared to the s.c. route. In
the same vein, a clinical study conducted in 249 patients reported results of inhala-
tional insulin that can be compared with that of s.c. insulin [49] . The same study also
reported the superiority of inhalational insulin over the s.c. route in terms of noninva-
siveness, better efficacy, and improved patient compliance.
8.8.3 Intranasal Administration
The advantages offered by the intranasal delivery of proteins are very comparable to
those of the inhalation route. The added feature of the intranasal route is that it can
also be used to target proteins and peptides to the brain. In the past decades, scien-
tists have been working extensively on using the intranasal route for delivering pep-
tide hormones like LHRH, calcitonin, and so forth.
In spite of various advantages of intranasal drug delivery for proteins, factors like
the type of delivery system, absorption profile, size, mucus turnover, and mucocili-
ary clearance became critical parameters for determining the pharmacokinetic profile
of peptide drugs. However, it is necessary to incorporate penetration and absorption
enhancers to promote nasal absorption of peptides with molecular weight exceeding
2000 Da.
Scientists have reported improved uptake and efficacy of leuprolide acetate, an
LHRH agonist using the intranasal liposomal base delivery system, and the efficacy
of exerting contraceptive action was found to be much improved as compared to con-
ventional formulations of the same drug [50] .
8.8.4 Peroral Administration
Bioavailability problems in orally administered peptides render the route useless
for peptide administration. Apart from susceptibility to acid and protease action, the