Oral Delivery of Proteins and Peptides: Concepts and Applications - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 508

slower drug release but relatively higher plasma concentration was seen at the later
time points [200] . Polymethacrylic acid- grafted -poly(ethylene glycol) have a capac-
ity to open tight junctions between epithelial cells in CACO-2 cell monolayers and
have hydrogeling properties; thus its nanoparticles have also been investigated for
oral protein delivery [201] .
10.6.8 Other Formulation Approaches
Protein endocytosis in enterocyte is effectively increased by noncovalent linking of
peptides to phospholipids. Insulin, calcitonin, porcine somatotropin, erythropoietin,
and -interferon have been effectively complexed with phospholipids to develop
effective oral formulations [202] . Enteric-coated microtablets containing insulin
along with cholate and trypsin inhibitor protect insulin from stomach pH. Protease
inhibitors protect drugs from proteolytic enzymes, and cholate increases the absorp-
tion of protein along with fatty acids [203] .
10.6.8.1 Cochleates
In a lipid-based system, cochleates have been demonstrated as a promising peptide
delivery system via oral route. They are mainly composed of phosphatidylserine,
cholesterol, and calcium. The phospholoid bilayer acquires a spiral shape, whereas in
liposomes they are in the form of concentric bilayers. Cochleates do not contain an
internal aqueous core. Cochleates have shown several advantages such as enhanced
stability, nontoxic nature, and ease of lyophilization as well as effective delivery of
peptides to mucosa [204] . Though there are several advantages, very little work has
been done on cochleates, and thus only a small amount of information is available
about this delivery system.
10.6.8.2 Polymersomes
Polymersomes are composed of hydrophilic-hydrophobic block copolymer, arranged
in a bilayer vesicular system having a central aqueous core. They have a hydrophilic
inner core and lipophilic bilayer, hence can be used for both hydrophilic and lipo-
philic drugs. They differ from nanoparticles in that they contain a hydrophilic core
rather than a lipophilic core, as in the case of nanoparticles [205] . Although they
have a bilayer structure, they offer more stability than liposomes due to the presence
of a thick and rigid bilayer. They contain a hydrophilic core that provides a protein-
affable environment. The PEG chain is generally present as a hydrophilic block in
most of the research carried out so far. Because proteins have the tendency to move
away from the PEG chain, their entrapment in such a vesicular system is much less
than 5% [206] .
10.6.8.3 Polymeric Micelles
Polymeric micelles are also composed of hydrophilic-hydrophobic block copolymers.
Today, they are gaining attention to deliver a wide variety of bioactives [207] . They