POLYMERIC CD-NANOPARTICLES FOR THE SIMULTANEOUS DELIVERY OFTHERAPEUTICS TO TREAT SEVERE DISEASES

Cancer and drug-resistant bacterial infections are two of the biggest health threats that humankind is facing. In fact, cancer causes nowadays 9.6 million deaths/year and drug-resistantinfections are expected to reach the same figures by 2050. EC engages in supporting anincreasing number of research projects for innovative solutions to overcome drawbacks ofcurrently employed therapeutics. The ITN CyclonHit and the MSCA-IF Polar Star projects aretwo examples of EC commitment and focus on cyclodextrin (CD)-based nanocarriers toencapsulate, protect and potentiate known drugs to fight resistant bacteria and prostate cancer,respectively.In the frame of CyclonHit project, we developed biocompatible and biodegradablepolymeric CD nanoparticles (pCD NPs) able to coencapsulate by a “green” method two potentanti-tuberculosis molecules which are insoluble in biologically-compatible solvents. Theformulation process was complicated by the completely different physico-chemical properties ofthe two active agents and by the strong tendency to crystallize of one of them. The developedcarriers were spectroscopically characterized proving that the drugs were encapsulated at amolecular level not only in the CD cavities but also in the intermingled polymeric chains. Theefficacy of the developed NPs was demonstrated in vitro and in vivo. In particular, theaerosolized NPs suspension led to a 3-log decrease of the pulmonary bacterial load of infectedanimals after only 6 administrations. Interestingly, the unloaded pCD NPs exhibited themselvesa good antibacterial effect contributing to the action of the two active molecules.In the frame ofPolar Star, CD-based NPs are tailored to increase the effectiveness and the specificity ofknown drugs against castrate-resistant prostate cancer. The NPs are composed of innovativemixed polymers combining α, β and γ-CD in single polymers to improve loading capacity fordifferent therapeutic agents. The final goal is to exploit multicargo NPs able to act acrossmultiple oncogenic pathways