Callerio Foundation

Microsphere

Outline of activity

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.


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