FUNCTIONALISED NANOPARTICLES LOADED WITH DRUGS: A NEW TOOL AGAINST PNEUMOCOCCAL GROWTH AND BIOFILM FORMATION

Streptococcus pneumoniae is one of the deadliest bacterial pathogens with high clinical significance in invasive pneumococcal disease (IPD). Vaccines have reduced the burden of disease caused by S. pneumoniae, but the increase in antibiotic-resistant strains and serotypes not covered by vaccines is concerning. Therefore, the development of new therapies to prevent and treat this disease is crucial. The efficacy of nanoparticles developed by the Rocasolano Institute of Physical Chemistry (CSIC) was evaluated. These nanoparticles were functionalised with vitamin E and loaded with three hydrophobic drugs—a macrolide, an antihistamine, and a glucocorticoid—and combinations thereof, both in biofilm and in planktonic culture of S. pneumoniae . Three strains of pneumococcus were used for this purpose: a reference strain of serotype 19F, an isogenic mutant of serotype 19A, and a multidrug-resistant clinical strain also of this serotype. It was observed that, in the reference strain, both empty nanoparticles and combinations with drugs inhibited growth at concentrations of 1.25% or 2.5%. Even when using nanoparticles with combinations of macrolide and the other two drugs, a decrease to 0.7% and 1.25% was observed. In the case of the isogenic mutant, this effect was also observed in viability but at higher concentrations, and with the multidrug-resistant strain, a decrease in growth was observed with the nanoparticle loaded with the antihistamine and the nanoparticle loaded with the combination of this together with the macrolide. In the inhibition of the biofilm of the reference strain, it was observed that the three loaded nanoparticles inhibit the biofilm at concentrations higher than the minimum inhibitory concentration, and in the case of the combinations, the macrolide nanoparticle with the glucocorticoid and the triple combination of the three drugs in the nanoparticle show an effect. However, in the treatment of biofilm, greater disintegration is observed when empty nanoparticles are used rather than loaded ones, which differs from what occurs in inhibition. Nanoparticles loaded with different types of drugs and combinations thereof show a notable effect in inhibiting the growth of pneumococcus and even in inhibiting the biofilm of this pathogen. The nanoparticle loaded with the antihistamine has the greatest growth-inhibiting effect, and in the case of biofilm inhibition, the three loaded nanoparticles, as well as the combination of macrolide with glucocorticoid and the triple combination, show the greatest effect. These strategies may be presented as alternatives for the prevention and treatment of this disease.