The microsystems are being
developed with the goal to orally
deliver biologically active
principles (BAPs), such as vaccines,
proteins, drugs, hormones etc.,
usually administered throughout
invasive routes (for instances,
intravenously, intramuscularly,
subcutaneously), with the aim
to protect them and to facilitate
their absorption and release
at the gut level.
Composition
The microsystems described
in the international patent
WO 2005/013941, present a mean
diameter of about 3 µm
(after hydration it changes
only of 18 %). This parameter
facilitates the process of uptake
of the particles at the GALT
(gut associated lymphoid
tissue) level, warranting
a greater presence of the BAPs
contained, particularly within
the Peyer’s
patches (PP).
Several
studies have pointed out that
particles with a diameter comprised
between 5 and 10 µm remain
in the PP, while those with
diameter lower than 5 µm
are transported, by the efferent
lymph pathways, at the mesenteric
level, in the liver and the
spleen. Particles with diameter
greater than 10 µm, conversely
are not taken up by the intestinal
mucosa and release their content
in the gut lumen.
Dimension management
The microsystems are
constituted of an alginate
core, gelified in the presence
of calcium ions, stabilized
with hydroxopropylcellulose
(HPMC), and containing lyzozyme
associated to the biologically
active principle, then coated
with chitosan, a constituent
able to confer muco-adhesive
properties to the system.
Adhesion, uptake
and release
The microsystem presents a
positive value of zeta
potential (or superficial
charge), equal to 2,1±0,6
mV. Apart the particle dimension,
this parameter influences also
the process of uptake of the
microsystem at the PP level,
in that it influences the capacity
of the microparticles to adhere
to the mucous stratum.
In fact,
the presence of positively charged
particles, may lead to electrostatic
interactions between the mucosa
and the particles themselves,
given that the mucous stratum
is a linear polyelectrolyte
negatively charged, at pH values
proximal to neutrality.
The microparticles taken up
by PP, are then degraded and
can release
their content . This release
process is favoured by the physico-chemical
characteristics of the microsystem.
In fact, it is able to protect
BAPs against the degrading effects
of the stomach, resulting resistant
to degradation in acidic pH,
and to facilitate the release
of their content in alcaline
pH, typical of the first part
of the gut rich of lymphoid
organs (in both mammalians and
fishes). Changing the percent
of the components used for the
preparation of the microparticles,
it is possible to modulate
the releasing properties
of the content as a function
of the ‘needs’ of
the transported molecule.
| BIOPOD |
 |
On April 2007, in the frame
of the SpinArea-Innovation Factory
programme, the Callerio Foundation
Onlus started-up a pre-competitive
initiative with the goal to
develop, realize and market
“Microspheres useful
in human and veterinary medicine,
suitable to deliver drugs and
vaccines through the oral route
and useful also in the nutraceutical
field”.
With the perspective to enter
the market with commercial and
advertising actions of products
based on the principle of the
microsphere, it has been adopted
the tradename of biopod,
where ‘biopod’ may
represent the acronym ‘biological
principles oral delivery’
and where ‘pod’
is intended as an ‘envelope’.
The microsystem for the commercial
development showed to be very
versatile as a system for oral
delivery, also thanks to the
many activities
of lysozyme. ). Furthermore,
the inventor novelty, described
in the patent,
represents the reference point
for its potential use in humans
and animals; in both cases with
an important impact for human
health.
In the preliminary and widening
of the potential market and
of the approval of this microsystem,
the Microsphere group has identified
four strategic targets :
a) ornamental
fishes
b) Fish
in intensive breeding
c) nutraceutics
d) diabetes
