Protein and Peptide Delivery through Respiratory Pathway - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 436

using microparticles as vehicles, the influence of these clearance mechanisms may be
attenuated, and more efficient absorption and a sustained therapeutic effect may be
achieved. The development of novel drug delivery systems led to the designing of a
drug-loaded delivery system for enhanced bioavailability, effective therapy, improved
clinical efficiency, and cost effectiveness. New drug delivery systems are being inves-
tigated, such as inhaled aerosols or DPIs with precise control over particle size and
density, with particles between 1 and 5 m in aerodynamic diameter, in order to maxi-
mize peripheral lung deposition.
9.5 Intranasal Delivery of Peptides and Proteins
9.5.1 Use of the Nasal Cavity for Drug Administration
In ancient times, different snuffs like cocaine and tobacco were used for the halluci-
nogenic effects. In recent years, use of the nasal cavity for the delivery of challenging
drugs, particularly peptides and proteins, has created much interest, not only for local
delivery of drugs but also for systemically acting drugs. Systemic delivery is required
in critical conditions where a rapid onset of action is needed and for long-term treat-
ment where drug administration is daily. The parenteral route is not suitable for the
long-term therapy. Currently, several peptide-based nasal formulations have entered
the market. The world market has seen an increasing number of systemically acting
drugs being marketed as intranasal formulations [33] . Due to increasing demands for
new highly potent drug formulations, more attention is being paid to the intranasal
delivery system, as it offers several advantages such as rapid absorption into systemic
circulation, avoidance of degradation in the gastrointestinal (GI) tract, elimination of
first-pass hepatic metabolism, and minimal proteolytic activity in the nasal mucosa,
as well as improved bioavailability of not only small but also large drug molecules.
Research work carried out in many laboratories has shown that, with the exception of
a few peptides, drugs with distinct chemical structures are well absorbed through the
nasal membranes of both animals and humans. Many authors consider in vivo nasal
absorption of drugs with molecular weights less than 300 Da not to be significantly
influenced by physicochemical properties of the drug molecule [34] .
Alternative routes of administering drug delivery to the brain with less invasive tech-
niques, such as nasal drug delivery, have been reported by different authors [35-37] .
Intranasal administration allows drugs that do not cross the blood-brain barrier (BBB)
to be delivered to the central nervous system (CNS) within minutes. In the recent past,
many patents have been filed on delivering a therapeutic agent for brain targeting due
to the high permeability of the nasal epithelium; as the brain and nose compartments
are connected to each other via the olfactory/trigeminal route and via peripheral circu-
lation [38] , this allows a higher molecular mass cut-off of approximately 1000 Da, and
the rapid drug absorption rate with plasma drug profiles is sometimes almost identi-
cal to those from intravenous administrations [39] . The clinically used anticancer and
reproductive drug GnRH was one of the peptides shown to possess neurotransmitter
function [40,41] . It is delivered by intranasal administration and is able to cross the