(598e) Encapsulation of Poorly Water-Soluble Drugs into Yeast Glucan Particles By Spray Drying: Improvement of Dispersion and Dissolution Properties

Encapsulation
of poorly water-soluble drugs into yeast glucan particles by spray drying:
Improvement of dispersion and dissolution properties

Gabriela
Ruphuy^*,
Ivan
Saloň, Jan Tomas, Petra
Šalamunová, Jaroslav Hanus, František Štepánek

Department
of Chemical Engineering, University of Chemistry and Technology Prague,
Technická 3, 166 28 Prague 6, Czech Republic

^*E-mail: ruphuycg@vscht.cz

Yeasts
are single-celled microorganisms belonging to the fungus kindom. They are more
commonly known for their use in food products and, in the biomedical field,
they have been of great interest for drug delivery. The so-called yeast glucan
particles (GP) are obtained after removing all the internal organelles and cell
wall components, other than β-glucans, from Saccharomyces cerevisiae (baker’s yeast). The result are hollow and
porous shells which are suitable for drug encapsulation. Since they are
obtained from microorganisms, they activate pattern recognition receptors of
host immune cells, triggering immune responses [1].
For this reason, most of the studies have been focused on the use of GP for the
encapsulation and macrophage-targeted delivery of drugs.

Peptides
[2], liposomes [3], siRNA [4], DNA [5], among others water-soluble payloads,
have been successfully encapsulated into GP for macrophage-targeted delivery.
Publications on the encapsulation of poorly-water soluble drugs, on the other
hand, are scarse, constituting an area of study yet to explore. Low
water-soluble resveratrol, for instance, was encapsulated in living yeast [6], and curcumin, also insoluble in water, was
loaded in 1,3-β-glucan isolated from mushrooms [7]. Given that GP are mainly composed of  amorphous polysaccharides (>85% β-glucans),
they are suitable candidate-materials for the development of amorphous solid
dispersions (ASDs). To the best of our knowledge, no studies are found either
regarding the encapsulation of low-water soluble drugs in beta-glucan particles
by spray drying, or regarding the use of beta-glucan particles for the
amorphization of low water-soluble drugs.

In
this work, low water-soluble drug models, such as ibuprofen (IBU) and curcumin
(CC), were loaded into GP using spray drying. Microparticles with different IBU-to-GP
mass ratios were prepared and characterized. Samples with low IBU content (20%
or less) exhibited amorphous state, but crystallinity peaks appeared and
increased with drug content. The presence of IBU crystals outside the GP was
observed in the case of the samples with higher IBU/GP mass ratio (>20% IBU).
This was evident also in the XRD results.

Different
sets of spray-drying parameters were tested to evaluate the influence of
droplet size and initial solid content on encapsulation efficiency (EE). It was
determined that both, droplet size and initial solid content, have an influence
on EE, but the effect of droplet size seems to be more significant; larger
droplet sizes lead to higher encapsulation efficiencies. For instance,
approximately 100% EE was obtained for a CC/GP composite sample produced using
an ultrasonic nozzle (USN), whereas a drug content of 61.5 %  was obtained for the CC/GP sample prepared using
the 2-fluid nozzle (2FN). With the USN, much larger droplets are produced than
with the 2FN under the conditions used. Therefore, the difference in EE is
attributed to losses of curcumin that precipitated outside of the glucan
particles in the case of the 2FN-sample due to a smaller droplet size (see Fig. 1). Such curcumin particles are
very small; therefore, there is a high possibility that they were not collected
in the cyclone, causing the losses along the spray dryer.

Figure 1. Confocal microscopy images of YGP/CC produced with 2-fluid nozzle (left side), and ultrasonic
nozzle (right side).

Lastly, dissolution kinetics were
evaluated for IBU/GP composites produced using the USN, and physical mixtures
of the composites with crude crystalline ibuprofen. Progressively faster
dissolution profiles (see Fig. 2) were
obtained with increasing mass fraction of the composites, until the solubility
limit was reached. In fact, the fast release of the IBU/GP composites lead to supersaturation,
a typical characteristic of ASD. This is an important property because, if the supersaturated state is maintained
for sufficient time, the in-vivo drug
absorption may increase, resulting in an overall improved oral bioavailability [8-10]. Finally, besides fast dissolution,
these IBU/GP composites exhibited outstanding
wettability and dispersion properties.

Figure
2. Dissolution
kinetics of crude ibuprofen, IBU/GP composites prepared with ultrasonic nozzle, and physical mixtures of them (e.g.
mixture 75/25 = 75 wt.% of crude ibuprofen and 25 wt.%
of IBU/GP composites).

Acknowledgements.
Authors
acknowledge financial support by the European Structural and Investment Funds,
OP RDE-funded project 'CHEMFELLS4UCTP' (No. CZ.02.2.69/0.0/0.0/17_050/0008485),
and by the Agency for Healthcare research, project no. 16-27522A.

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