Protein and Peptide Delivery through Respiratory Pathway - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 446

nanoparticles are capable carriers for the transnasal absorption of drugs and proteins.
Chitosan-based nanoparticles enhance nose-to-brain delivery of drugs compared to
equivalent drug solutions formulations because the drug is protected from degradation
and/or efflux back into the nasal cavity [116].

9.5.3.2.6.3 are composed of charged com-

ponents, stearylamine, dicetyl phosphate, and some bioadhesive material for the prepara-
tion of liposomes. Positively charged liposomes provide maximum bioadhesion, thereby
prolonging the residence time within the nasal cavity and thus increasing bioavailability.
Vyas et al. have prepared multilamellar liposomes for intranasal delivery of nifedipine
[117]. Shim et al. have successfully prepared and evaluated free-flowing proliposomes
containing propranolol hydrochloride for transnasal delivery of propranolol [118].
9.5.3.2.6.4 Micelles Micelles are formed by the self-assembly of amphiphilic
block copolymers in aqueous solutions and are of great interest as a novel drug deliv-
ery system [119]. Tengamnuay and Mitra have reported a synergistic effect on the
nasal absorption of peptides by utilizing mixed micelles of bile salts and fatty acid
[120]. Micellar nanocarriers of zolmitriptan to treat migraine have been developed
and evaluated effectively as potential carriers for nose-to-brain delivery by Patravale
et al. [121] .

Liposomes and Proliposomes Liposomes

9.5.3.3 Delivery Device-Related Factors
A successful nasal formulation program involves detailed consideration of the inter-
actions between formulation composition, device design, delivery system, and the
patient's pathological condition. Different types of intranasal delivery devices are
utilized. Both (i) the size of the droplet or powder and (ii) the site and pattern of
deposition affect the intranasal permeation of drugs.

9.5.3.3.1 Size of the Droplet or Powder
The particle size of the droplet produced depends on the delivery device used. The par-

ticles will be deposited in the upper respiratory tract if the particle size produced is less
than 10

μ m, whereas if the particles are less than 0.5 μ m, they will be exhaled. Particles

or droplets of size between 5 and 7 μ m will be retained in the nasal cavity [122].

9.5.3.3.2 Site and Pattern of Drug Deposition
The site and pattern of drug deposition is affected by the formulation composition,
the dosage form, the delivery device used, the design of actuators and adapters,
and the administration technique. Drug absorption is also affected by the area of
nasal cavity exposed and the permeability of the deposition site. These factors also
decide the retention time of the drug in the nasal cavity.

9.5.4 Methods of Overcoming the Barriers to Absorption
9.5.4.1 Absorption Enhancers
Due

to the size of macromolecule drugs, mostly proteins and peptides, they cannot nat-
urally and efficiently pass through the nasal membranes without the use of penetration